Right at the moment while we are learning or forming new information, our brain generates fascinating synaptic signals called Long-Term Potentiation (LTP), a neurophysiological process underlying learning and memory formation. During this process, the brain generates synaptic signals that can be recorded as time-series waveforms using techniques such as Microelectrode Arrays (MEA). These signals, particularly the first field excitatory postsynaptic potential (fEPSP), rapidly change in response to stimulation, pharmacological intervention, or subtle pathological alterations, thereby capturing biologically meaningful information regarding synaptic strength and temporal dynamics.
However, current LTP analysis methods suffer from major limitations. Most studies rely on oversimplified analytical approaches without validating whether waveform changes truly represent synaptic activity or drug-specific effects. Synaptic regions are often manually selected, while statistical methods are frequently applied without verifying assumptions such as data normality. Furthermore, standardized quality control procedures for detecting artifacts, noise, waveform heterogeneity, or batch effects are often lacking.
To address these challenges, we developed LTP Analysis Software, a standardized platform for LTP waveform analysis. The platform performs waveform preprocessing, synaptic region detection, noise removal, artifact detection, unsupervised clustering, feature extraction, and interpretable supervised machine learning.
We evaluated the software using electrophysiological recordings from over 50 idiopathic Normal Pressure Hydrocephalus (iNPH) patients, a cohort in which approximately 50% of cortical biopsies exhibit early Alzheimer's Disease (AD)-related pathology. Using Random Forest classification with group cross-validation, the framework achieved 92% accuracy in pathology prediction, suggesting that different pathological conditions are associated with distinct LTP waveform signatures.

Co-authors: Mireia Gómez-Budia, Anssi Pelkonen, Tarja Malm, Luca Giudice