Rhythmic oscillations within the 3-12 Hz theta frequency band manifest in the rodent hippocampus during a variety of behaviors and are particularly well characterized during spatial navigation. In contrast, previous studies of rhythmic hippocampal activity in primates under comparable behavioral conditions suggest it may be less apparent and possibly less prevalent, or even absent, compared to the rodent. We compared the relative presence of low frequency oscillations in rats and humans during spatial navigation by employing an oscillation detection algorithm (“P-episode” or “BOSC”) to better characterize their presence in microelectrode local field potential (LFP) recordings. This method quantifies the proportion of time the LFP exceeds both a power and cycle duration threshold at each frequency, characterizing the presence of 1) oscillatory activity compared to background noise, 2) the peak frequency of oscillatory activity, and 3) the duration of oscillatory activity. Results demonstrate that both humans and rodents have hippocampal rhythmic fluctuations lasting, on average, 2.75 and 4.3 cycles, respectively. Analyses further suggest that human hippocampal rhythmicity is centered around ~3Hz while that of rats is centered around ~8Hz. These results establish that low frequency rhythms relevant to spatial navigation are present in both the rodent and human hippocampus, albeit with different properties under the behavioral conditions tested.

More than 5,000,000 survivors of traumatic brain injury (TBI) live with persistent cognitive deficits, some of which likely derive from hippocampal dysfunction. Oscillatory activity in the hippocampus is critical for normal learning and memory functions, and can be modulated using deep brain stimulation techniques. In this pre-clinical study, we demonstrate that lateral fluid percussion TBI results in the attenuation of hippocampal theta oscillations in the first 6 days after injury, which correlate with deficits in the Barnes maze spatial working memory task. Theta band stimulation of the medial septal nucleus (MSN) results in a transient increase in hippocampal theta activity, and when delivered 1 min prior to training in the Barnes maze, it significantly improves spatial working memory. These results suggest that MSN theta stimulation may be an effective neuromodulatory technique for treatment of persistent learning and memory deficits after TBI.

Traumatic brain injury (TBI) often results in persistent attention and memory deficits that are associated with hippocampal dysfunction. Although deep brain stimulation (DBS) is used to treat neurological disorders related to motor dysfunction, the effectiveness of stimulation to treat cognition remains largely unknown. In this study, adult male Harlan Sprague-Dawley rats underwent a lateral fluid percussion or sham injury followed by implantation of bipolar electrodes in the medial septal nucleus (MSN) and ipsilateral hippocampus. In the first week after injury, there was a significant decrease in hippocampal theta oscillations that correlated with decreased object exploration and impaired performance in the Barnes maze spatial learning task. Continuous 7.7 Hz theta stimulation of the medial septum significantly increased hippocampal theta oscillations, restored normal object exploration, and improved spatial learning in injured animals. There were no benefits with 100 Hz gamma stimulation, and stimulation of sham animals at either frequency did not enhance performance. We conclude, therefore, that there was a theta frequency-specific benefit of DBS that restored cognitive function in brain-injured rats. These data suggest that septal theta stimulation may be an effective and novel neuromodulatory therapy for treatment of persistent cognitive deficits following TBI.

Summary Low-frequency (delta/theta band) hippocampal neural oscillations play prominent roles in computational models of spatial navigation but their exact function remains unknown. Some theories propose they are primarily generated in response to sensorimotor processing while others suggest a role in memory-related processing. We directly recorded hippocampal EEG activity in patients undergoing seizure monitoring while they explored a virtual environment containing teleporters. Critically, this manipulation allowed patients to experience movement through space in the absence of visual and self-motion cues. The prevalence and duration of low-frequency hippocampal oscillations were unchanged by this manipulation, indicating that sensorimotor processing was not required to elicit them during navigation. Furthermore, the frequency-wise pattern of oscillation prevalence during teleportation contained spatial information capable of classifying the distance teleported. These results demonstrate that movement-related sensory information is not required to drive spatially informative low-frequency hippocampal oscillations during navigation and suggest a specific function in memory-related spatial updating.

iCT can be easily incorporated into standard DBS surgery, replaces the need for C-arm fluoroscopy, and provides accurate intraoperative 3-dimensional confirmation of electrode tip locations relative to preoperative images and surgical plans. iCT fused to preoperative MRI may obviate the need for routine postoperative MRI in DBS surgery. Technical nuances that must be mastered for the efficient use of iCT during DBS implantation are described.

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Damage to the medial temporal lobes produces profound amnesia, greatly impairing the ability of patients to learn about new associations and events. While studies in rodents suggest a strong link between damage to the hippocampus and the ability to navigate using distal landmarks in a spatial environment, the connection between navigation and memory in humans remains less clear. Past studies on human navigation have provided mixed findings about whether patients with damage to the medial temporal lobes can successfully acquire and navigate new spatial environments, possibly due, in part, to issues related to patient demographics and characterization of medial temporal lobe damage. Here, we report findings from a young, high functioning patient who suffered severe medial temporal lobe damage. Although the patient is densely amnestic, her ability to acquire and utilize new, but coarse, spatial “maps” appears largely intact. Specifically, a novel computational analysis focused on the precision of her spatial search revealed a significant deficit in spatial precision rather than spatial search strategy. These findings argue that an intact hippocampus in humans is not necessary for representing multiple external landmarks during spatial navigation of new environments. We suggest instead that the human hippocampus may store and represent complex high-resolution bindings of features in the environment as part of a larger role in perception, memory, and navigation.

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