Understanding how the brain regulates its own activity is central to modern psychiatry. One important mechanism is inhibition, the brain’s ability to quiet overactive circuits. A growing body of research now uses TMS-EEG GABAb inhibition measures to study this process directly in living patients. A 2025 study published in Progress in Neuro-Psychopharmacology and Biological Psychiatry highlights how these measures differ between schizophrenia, bipolar disorder, and healthy individuals, offering new insight into diagnosis and treatment.
How TMS-EEG Measures Cortical Inhibition
Transcranial magnetic stimulation combined with electroencephalography allows researchers to stimulate the cortex while recording the brain’s electrical response in real time. In paired pulse paradigms, two magnetic pulses are delivered with a brief delay. The second response is normally suppressed by inhibitory signaling mediated by GABAb receptors. This suppression is called long interval cortical inhibition, or LICI. Lower LICI values indicate weaker inhibitory control, suggesting difficulty calming neural activity after stimulation.
Key Findings In Schizophrenia And Bipolar Disorder
In this study, researchers compared LICI values in people with schizophrenia, bipolar disorder, and healthy controls. Patients with schizophrenia showed significantly reduced LICI compared with controls, indicating impaired GABAb mediated inhibition. In contrast, individuals with bipolar disorder did not show the same reduction. This distinction is important because schizophrenia and bipolar disorder often share overlapping symptoms, yet their underlying brain physiology may differ in measurable ways.
Links To Cognition And Symptoms
Reduced TMS-EEG GABAb inhibition in schizophrenia was not just a laboratory finding. Lower LICI values were associated with worse cognitive performance and more severe positive symptoms such as hallucinations and delusions. This suggests that inhibitory deficits are not incidental but may contribute directly to how symptoms emerge and persist. From a clinical perspective, this strengthens the case that disrupted inhibition is a core feature of schizophrenia rather than a side effect of medication or illness duration.
Medication Effects And What They Mean
The researchers also examined whether common psychiatric medications explained the inhibitory differences. Benzodiazepines increased LICI values, consistent with their known effects on inhibitory signaling. However, this medication effect did not account for the reduced inhibition seen in schizophrenia. This finding reinforces the idea that impaired GABAb function reflects an underlying pathophysiological process rather than simple drug exposure.
Why This Matters For Precision Psychiatry
These findings highlight the promise of TMS-EEG GABAb inhibition as a biomarker. Rather than relying solely on symptom checklists, clinicians may eventually use neurophysiological signatures to identify biologically distinct subgroups within schizophrenia. Such markers could guide treatment selection, predict cognitive outcomes, or help monitor response to novel interventions aimed at restoring inhibitory balance.
Looking Ahead
As TMS-EEG methods continue to mature, they may become integral to interventional psychiatry. By directly measuring how the brain responds to stimulation, researchers can move closer to personalized care grounded in circuit level function. This study represents an important step toward that goal, showing how disrupted inhibition helps explain both the cognitive and clinical features of schizophrenia.
Citations
- Mijancos-Martínez G, Fernández-Linsenbarth I, Bachiller A, et al. Distinct cortical inhibitory profiles in schizophrenia and bipolar disorder: A TMS-EEG study of GABAb function. Prog Neuropsychopharmacol Biol Psychiatry. 2025; DOI: 10.1016/j.pnpbp.2025.111593. https://pubmed.ncbi.nlm.nih.gov/41455507/
- Premoli I, Rivolta D, Espenhahn S, et al. Characterization of GABAb receptor mediated neurotransmission in the human cortex by paired pulse TMS-EEG. NeuroImage. 2014; 103:152–162. https://doi.org/10.1016/j.neuroimage.2014.09.028