Fast Interneuron Dysfunction in Laminar Neural Mass Model Reproduces Alzheimer's Oscillatory Biomarkers

Early-stage AD involves cortical hyperexcitability, progressing to oscillatory slowing and hypoactivity. These changes are linked to parvalbumin-positive ( $\mathrm{PV}$ ) interneuron dysfunction and neuronal loss driven by amyloid-beta ( $\mathrm{A\beta }$ ) and hyperphosphorylated tau (hp- $\tau$ ), though underlying mechanisms remain unclear. To investigate this relationship, we employed a Laminar Neural Mass Model integrating excitatory and inhibitory populations. Synaptic coupling from $\mathrm{PV}$ interneurons to pyramidal cells was progressively reduced to mimic $\mathrm{A\beta }$ -induced neurotoxicity. Additional parameter variations simulated alternate mechanisms, including hp-tau pathology. Simulated dipole activity was analyzed in the time-frequency domain and compared to the literature. Simulating $\mathrm{PV}$ interneuron dysfunction reproduced AD's biphasic progression: early hyperexcitability with elevated gamma and alpha power, followed by oscillatory slowing and reduced spectral power. Alternative mechanisms, such as increased excitatory drive, did not replicate this trajectory. To account for late-stage hypoactivity and reduced firing rates, we incorporated pyramidal cell disruption consistent with hp- $\tau$ neurotoxicity. While not essential for local oscillatory changes, this addition aligns the model with empirical markers of advanced AD and supports whole-brain modeling. These findings highlight $\mathrm{PV}$ interneuron dysfunction as a primary mechanism of early electrophysiological disruption in AD, with pyramidal cell loss contributing to late-stage hypoactivity, offering a mechanistic model for excitation-inhibition imbalance across progression.