The theta rhythm-a slow (6-12 Hz) oscillatory component of the local field potential-plays a critical role in spatial navigation and memory by coordinating the activity of neuronal ensembles within the medial temporal lobe (MTL). Although theta has been extensively studied in freely moving rodents, its presence in humans has been elusive and primarily investigated in stationary subjects. Here we used a unique clinical opportunity to examine theta within the human MTL during untethered, real-world ambulatory movement. We recorded intracranial electroencephalographic activity from participants chronically implanted with the wireless NeuroPace responsive neurostimulator (RNS) and tracked their motion with sub-millimeter precision. Our data revealed that movement-related theta oscillations indeed exist in humans, such that theta power is significantly higher during movement than immobility. Unlike in rodents, however, theta occurs in short bouts, with average durations of ∼400 ms, which are more prevalent during fast versus slow movements. In a rare opportunity to study a congenitally blind participant, we found that both the prevalence and duration of theta bouts were increased relative to the sighted participants. These results provide critical support for conserved neurobiological characteristics of theta oscillations during ambulatory spatial navigation, while highlighting some fundamental differences across species in these oscillations between humans and rodents.

The hippocampus is critical for episodic memory, and synaptic changes induced by long-term potentiation (LTP) are thought to underlie memory formation. In rodents, hippocampal LTP may be induced through electrical stimulation of the perforant path. To test whether similar techniques could improve episodic memory in humans, we implemented a microstimulation technique that allowed delivery of low-current electrical stimulation via 100 μm-diameter microelectrodes. As thirteen neurosurgical patients performed a person recognition task, microstimulation was applied in a theta-burst pattern, shown to optimally induce LTP. Microstimulation in the right entorhinal area during learning significantly improved subsequent memory specificity for novel portraits; participants were able both to recognize previously-viewed photos and reject similar lures. These results suggest that microstimulation with physiologic level currents—a radical departure from commonly used deep brain stimulation protocols—is sufficient to modulate human behavior and provides an avenue for refined interrogation of the circuits involved in human memory.

Anxiety is a widely studied phenomenon in behavioral neuroscience, but the recent literature lacks an overview of the major conceptual framework underlying anxiety research to introduce young researchers to the field. In this mini-review article, which is aimed toward new undergraduate and graduate students, we discuss how researchers exploit the approach-avoidance conflict, an internal conflict rodents face between exploration of novel environments and avoidance of danger, to inform rodent assays that allow for the measurement of anxiety-related behavior in the laboratory. We review five widely-used rodent anxiety assays, consider the pharmacological validity of these assays, and discuss neural circuits that have recently been shown to modulate anxiety using the assays described. Finally, we offer related lines of inquiry and comment on potential future directions.

Theta oscillations play a critical role in learning and memory by coordinating the spiking activity of neuronal ensembles via mechanisms such as spike timing dependent plasticity 1-7 . This rhythm is present in rodents where it is continuously evident during movement at frequencies within 6-12Hz 8,9 . In humans, however, the presence of continuous theta rhythm has been elusive; indeed, a functionally similar theta is thought to occur at lower frequency ranges (3-7Hz) and in shorter bouts 10-12 . This lower frequency theta rhythm is observed during a variety of behaviors, including virtual navigation, but has never been tested during real world ambulatory movement. Here we examined the oscillatory properties of theta within the human medial temporal lobe (MTL) in freely moving human subjects chronically implanted with the clinical NeuroPace RNS ® responsive neurostimulator device, capable of wireless recordings of continuous intracranial deep brain electroencephalographic (iEEG) activity. MTL iEEG recordings, together with sub-millimeter position tracking, revealed the presence of high frequency theta oscillations (6-12Hz) during ambulation. The prevalence of these oscillations was increased during fast movement compared to slow movement. These theta bouts, although occurring more frequently, were not significantly different in durations during fast versus slow movements. In a rare opportunity to study one subject with congenital blindness, we found that both the prevalence and duration of theta bouts were much greater than those in sighted subjects. Our results suggest that higher frequency theta indeed exists in humans during movement providing critical support for conserved neurobiological mechanisms for spatial navigation. The precise link between this pattern and its behavioral correlates will be an exciting area for future studies given this novel methodology for simultaneous motion capture and long term chronic recordings from deep brain targets during ambulatory human behavior.