Introduction

The Laminar Neural Mass Model (LaNMM) is a computational framework developed to link circuit-level mechanisms to EEG/MEG biomarkers across various brain states, encompassing healthy function, disease, and altered consciousness.

Foundational Work

LaNMM Framework (2019, 2022):

These studies introduced a physics-grounded neural mass model capable of generating both alpha/beta and gamma oscillations across cortical layers. The model embeds synaptic sources into a spatially layered medium, enabling simulation of laminar LFPs and their spectral features.

Key Insights

  • Alpha/beta (slow/fast) rhythms are generated in deep layers, while gamma rhythms originate in superficial layers.
  • The model’s structure allows for the simulation of realistic depth-resolved LFP, bipolar LFP, and CSD, aligning with experimental macaque data and uncovering oscillatory origins.

Applications of LaNMM

Alzheimer’s Disease (AD) Study (2025)

This study simulates fast interneuron (PV+) dysfunction and later-stage pyramidal cell loss, reproducing AD’s biphasic M/EEG trajectory: early hyperexcitability (↑gamma, ↑alpha), followed by slowing and hypoactivity.

Mechanistic Findings:

  • Aβ oligomers impair PV+ interneurons leading to disinhibition and hyperactivity.
  • Subsequent tau pathology affects pyramidal neurons, resulting in hypoactivity.
  • PV+ dysfunction alone explains early-phase EEG biomarkers, but tau-induced hypoactivity is necessary to match reduced firing/metabolism in advanced stages.

Clinical Relevance:

The model suggests PV+ cells as therapeutic targets and EEG spectral changes as early-stage biomarkers, bridging molecular pathology and mesoscopic dynamics.

Psychedelics and AD (2024)

In this study, LaNMM is embedded in whole-brain models personalized to AD patients. Activation of 5-HT2A receptors (mimicking psychedelics) increases excitability in L5 pyramidal cells, counteracting AD-related oscillatory deficits.

Restoration of Dynamics:

  • Decreased alpha power (reduces hypersynchrony)
  • Increased gamma power (restores PV-related processing)
  • Increased entropy/complexity (a proxy for cognitive flexibility)

Spatial Specificity:

Spectral changes correlate with PET-derived 5-HT2A receptor distributions, suggesting that psychedelics could restore oscillatory dynamics in AD via targeted circuit modulation.

Prediction Error and Cross-Frequency Coupling (CFC) (2025)

This paper proposes that LaNMM supports biologically plausible comparator functions via cross-frequency coupling (CFC), enabling local prediction error evaluation in predictive coding.

Key Mechanisms:

  • Signal-Envelope Coupling (SEC): Low-frequency rhythms modulate the amplitude of fast oscillations (PAC-like).
  • Envelope-Envelope Coupling (EEC): Slow envelopes modulate fast envelopes, allowing gating and precision weighting (analogous to Kalman gain).

Comparator Disruption Across Conditions:

  • In AD: Interneuron loss disrupts CFC, leading to inflated early prediction errors and their later suppression.
  • In Psychedelics: Increased gain weakens prediction precision, resulting in “relaxed beliefs” and increased error signaling.

Comparator Hypothesis:

CFC in LaNMM instantiates the analog version of the hierarchical XOR-like error computation central to predictive coding and the Kolmogorov Theory (KT)/Active Inference (AIF). This formalization bridges algorithmic models with real electrophysiology.

Conclusion

LaNMM provides a unified, mechanistic scaffold for studying:

  • Neurodegeneration (e.g., Alzheimer’s Disease)
  • Psychedelic states
  • Predictive inference
  • Oscillatory biomarkers
  • Interneuron dynamics It is a physically grounded, biophysically realistic platform that integrates structure, dynamics, and function, serving as a bridge between biology and theoretical models.

For further inquiries or collaborations, please contact Giulio Ruffini at giulio.ruffini@neuroelectrics.com.

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