DeNicola, A. L. | Search bioRxiv

bioRxiv2025

Transcranial Alternating Current Stimulation can disrupt or reestablish neural entrainment in a primate model of Parkinson's disease

Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation method which can affect brain oscillations by inducing neuronal entrainment through modulation of spike timings. tACS has high potential for clinical applications in many neurological disorders in which the stimulation can be delivered to modulate oscillatory activity and disrupt pathological brain oscillations. For instance, in Parkinsons Disease (PD), electrophysiological activity in the motor network often exhibits excessive and hyper-synchronized beta oscillations. However, the development of tACS as a therapeutic intervention for pathological oscillations requires the prior establishment of physiologically effective stimulation parameters. We recorded neuronal activity in the motor cortical area of three parkinsonian non-human primates and examined the influence of tACS-induced electric fields on neural firing patterns. We found that weak extracellular electric fields first disrupt beta-band spike timing patterns by changing the preferred spiking phase of neurons but eventually reestablish neural entrainment with altered phase preferences when electric fields are high. Additionally, we show that frequency-matched stimulation, when stimulation frequency corresponds to endogenous oscillatory activity, significantly enhances neural entrainment. Thus, tACS exhibits significant potential for controlling and modulating pathological oscillatory patterns in many neurological disorders such as PD.

neuroscience↗

bioRxiv2022

A prefrontal network model operating near steady and oscillatory states links spike desynchronization and synaptic deficits in schizophrenia

Schizophrenia results in part from a failure of prefrontal networks but we lack full understanding of how disruptions at a synaptic level cause failures at the network level. This is a crucial gap in our understanding because it prevents us from discovering how genetic mutations and environmental risks that alter synaptic function cause prefrontal network to fail in schizophrenia. To address that question, we developed a recurrent spiking network model of prefrontal local circuits that can explain the link between NMDAR synaptic and spike timing deficits we recently observed in a pharmacological monkey model of prefrontal network failure in schizophrenia. We analyze how the balance between AMPA and NMDA components of recurrent excitation and GABA inhibition in the network influence spike timing to inform the biological data. We show that reducing recurrent NMDAR synaptic currents prevents the network from shifting from a steady to oscillatory state in response to extrinsic inputs such as might occur during behavior. This explains how NMDAR synaptic deficits, implicated by genetic evidence as causal in schizophrenia, could prevent the emergence of 0-lag synchronous spiking in prefrontal local circuits during behavior, potentially disconnecting those circuits via spike-timing dependent mechanisms in the human disease.

neuroscience↗