Divergent responses of glutamatergic and GABAergic prefrontal neurons underlie changes in excitability following low and high frequency repetitive brain stimulation.

Background: Repetitive brain stimulation is hypothesized to bidirectionally modulate excitability, with low-frequency trains decreasing and high-frequency (>5 Hz) trains increasing excitability in the brain. However, most insights on the neuroplastic effects of repetitive stimulation protocols stem from non-invasive human studies (TMS/EEG) or from rodent slice physiology. Here, we developed a rodent experimental preparation enabling imaging of cellular activity during repetitive stimulation protocols in vivo to understand the mechanisms by which brain stimulation modulates excitability of prefrontal cortical neurons.

Manipulation of neuronal activity by an artificial spiking neural network implemented on a closed-loop brain-computer interface in non-human primates.

Closed-loop brain-computer interfaces can be used to bridge, modulate, or repair damaged connections within the brain to restore functional deficits. Towards this goal, we demonstrate that small artificial spiking neural networks can be bidirectionally interfaced with single neurons (SNs) in the neocortex of non-human primates (NHPs) to create artificial connections between the SNs to manipulate their activity in predictable ways.Spikes from a small group of SNs were recorded from primary motor cortex of two awake NHPs during rest.

Dynamically Adjusting Intertemporal Choice Task in Rodents.

Temporal discounting refers to the tendency for immediate rewards over delayed ones, assessed through intertemporal choice tasks where subjects choose between immediate low-value or delayed high-value rewards. Traditional rodent tasks often require extensive pre-task training, introducing species-specific biases and thus lower translational utility. We present a novel dynamically adjusting intertemporal choice task, where the delay for a large reward adjusts trial-by-trial based on prior choices.

Differential glutamatergic and GABAergic responses drive divergent prefrontal cortex neural outcomes to low and high frequency stimulation.

Background: Repetitive brain stimulation is hypothesized to bidirectionally modulate excitability, with low-frequency trains decreasing and high-frequency (>5 Hz) trains increasing activity. Most insights on the neuroplastic effects of repetitive stimulation protocols stem from non-invasive human studies (TMS/EEG) or data from rodent slice physiology. Here, we developed a rodent experimental preparation enabling simultaneous imaging of cellular activity during stimulation in vivo to understand the mechanisms by which brain stimulation modulates excitability of prefrontal cortex.

Optimized Theta Burst Stimulation with Extended Intervals Enhances Excitatory-Inhibitory Balance.

Electrical theta burst stimulation (TBS) with different inter-train intervals (ITIs) was first used to characterize bidirectional synaptic plasticity in brain slices. Despite a lack of understanding of mechanism, TBS has been adopted by rTMS research and clinical protocols to drive plasticity in the human brain, with variable results. To uncover how TBS modulates excitability in vivo, we systematically screen the impact of electrical TBS with different ITIs on rodent cortical neurons.

Responses of Cortical Neurons to Intracortical Microstimulation in Awake Primates.

Intracortical microstimulation (ICMS) is commonly used in many experimental and clinical paradigms; however, its effects on the activation of neurons are still not completely understood. To document the responses of cortical neurons in awake nonhuman primates to stimulation, we recorded single-unit activity while delivering single-pulse stimulation via Utah arrays implanted in primary motor cortex (M1) of three macaque monkeys. Stimuli between 5 and 50 μA delivered to single channels reliably evoked spikes in neurons recorded throughout the array with delays of up to 12 ms.

Neurochip3: An Autonomous Multichannel Bidirectional Brain-Computer Interface for Closed-Loop Activity-Dependent Stimulation.

Toward addressing many neuroprosthetic applications, the Neurochip3 (NC3) is a multichannel bidirectional brain-computer interface that operates autonomously and can support closed-loop activity-dependent stimulation. It consists of four circuit boards populated with off-the-shelf components and is sufficiently compact to be carried on the head of a non-human primate (NHP). NC3 has six main components: (1) an analog front-end with an Intan biophysical signal amplifier (16 differential or 32 single-ended channels) and a 3-axis accelerometer, (2) a digital control system comprised of a Cyclone V FPGA and Atmel SAM4 MCU, (3) a micro SD Card for 128 GB or more storage, (4) a 6-channel differential stimulator with ±60 V compliance, (5) a rechargeable battery pack supporting autonomous operation for up to 24 h and, (6) infrared transceiver and serial ports for communication.