Emma Osorio, SUCEDE predoctoral researcher, reviews ‘Prefrontal Oscillatory Slowing in Early-Course Schizophrenia Is Associated With Worse Cognitive Performance and Negative Symptoms: A Transcranial Magnetic Stimulation–Electroencephalography Study’ (Donati et al., 2024).
In clinical practice, schizophrenia remains a diagnostic and therapeutic challenge, particularly regarding cognition and negative symptoms. Recently, the SUCEDE group presented a bibliographic session analyzing a clinical study that utilizes combined TMS-EEG (Transcranial Magnetic Survey combined with Electroencephalography) to explore the neurobiological basis of these alterations in the early stages of the disorder.
Below, we break down the key points of this research and its relevance to modern medicine.
- The Concept of “Natural Frequency”
Beyond the power of a specific frequency band, this study focuses on the natural frequency of the cortical circuit. This is defined as the preferred frequency at which a specific circuit—in this case, the dorsolateral prefrontal cortex (DLPFC)—oscillates after being perturbed by a TMS pulse.
In healthy subjects: The natural frequency of the DLPFC typically resides within the Gamma range (approx. 32 Hz).
In patients with schizophrenia: A shift toward slower rhythms is observed, with the Beta band predominating (approx. 18 Hz).
- Key Findings: Early-Stage Schizophrenia
One of the primary values of this study is that it was conducted on patients with less than 3 years of disease progression. This allows researchers to rule out that the slowing is merely a consequence of chronic neurodegeneration or long-term antipsychotic use, suggesting instead that it is a core, primary trait of the illness.
Neurobiological Substrate: This frequency shift may reflect a dysfunction in the excitation/inhibition balance, specifically related to failures in the GABAergic interneurons (parvalbumin-positive) that orchestrate fast rhythms.
- Clinical and Cognitive Correlation
The study found significant correlations that have direct implications for patient prognosis:
Negative Symptomatology: Lower natural frequency (greater slowing) correlates with increased severity of negative symptoms.
Cognitive Deficits: Increased Beta-band power was associated with poorer performance in cognitive control and working memory tasks.
- Technical Considerations and Limitations
During the medical discussion, several critical aspects regarding the interpretation of these data were highlighted:
Medication Effects: Although the study attempts to control for this variable, there is ongoing debate as to whether D2 receptor blockade or benzodiazepine use could artificially enhance this slowing or the detected inhibitory activity.
Electric Field Modeling: It is suggested that future studies should use electric field modeling to adjust TMS intensity, thereby avoiding biases derived from individual cortical atrophy.
Conclusion for the Clinician
The use of TMS-EEG allows us to “interrogate” the prefrontal cortex directly without relying on the patient’s motivation or attention (as is often the case with conventional task-based EEG). Identifying that the prefrontal cortex operates at slower frequencies from the onset of the disorder opens the door to:
Biological subtyping of patients.
Development of neuromodulation therapies aimed at restoring Gamma frequency to improve cognitive outcomes.
Original Video: 15/01/2026 Bibliográfica – Prefrontal Slowing TMS-EEG (E. Osorio)