FY2018 has seen significant progress towards realizing our goals and objectives. We have continued our efforts capturing and analyzing intracranial recordings while participants engage in cognitive tasks designed to probe memory encoding and retrieval. Patients with medically refractory epilepsy receiving intracranial electrodes and surgical treatment at the Clinical Center have been recruited for these studies. We have also continued our work analyzing local field potential and single unit spiking activity captured from the basal ganglia during deep brain stimulation surgery for patients with Parkinsons disease. Our previous efforts have largely focused on understanding changes in human brain activity across spatial scales. At the larger scale, we have been exploring communication between brain regions. We have developed a metric of effective connectivity that is premised on the hypothesis that communication between brain regions occurs with consistent and stable timing. We have successfully related these measures of effective connectivity to measures of oscillatory coherence, and our recent analyses suggest that brain regions communicate neural activity through phase modulated bursts that are gated by coherent oscillations. We have also examined how traveling waves of activity at this larger scale may be relevant for the ability to move information across the brain, and how this may play a role in cognition. We have completed both projects and are currently preparing manuscripts describing these findings for submission. At the smaller scale, we have successfully collected single unit spiking activity from microelectrode arrays in several patients while they have participated in our cognitive tasks, and have developed automated processing pipelines to extract out spiking information in real-time. We are continuing to develop these methodological advances in order to use these tools on three main sets of studies. In the first set of studies, we have been interested in investigating human episodic memory formation. Using a paired associates episodic memory task, we have directly explored two separate aspects of this process. First, we have shown how the background brain activity that forms a neural representation of the context within which memories are experienced plays a role in memory encoding. When we experience stimuli every day, we form a neural representation of both the individual items and the context within which they occur. The extent to which we can retrieve distinct memories depends on how different these representations are. In our recent study, we have shown that if the background context changes more rapidly from moment to moment, which means that the neural patterns of activity from moment to moment are more different, it is easier to remember and distinguish different memories. We have described this work in a recent manuscript that is currently in the review process. In a second study, we were interested in how interactions between the medial temporal lobe and the lateral temporal cortex may play a role in memory retrieval. Specifically, we focused on ripples, which are a form of fast oscillatory activity that has been previously identified in the medial temporal lobe and that has been hypothesized to play a role in memory retrieval. We have shown that ripples are coupled between the medial temporal lobe and the lateral temporal lobe during successful retrieval, providing a potential neural mechanism by which activity in the medial temporal lobe triggers the recovery of neural activity associated with a memory in the cortex. We have described this work in a recent manuscript that is currently in the review process. In a second set of studies, we have been interested in understanding how the fidelity of memory encoding is modulated by the state of the brain. We have found that attention improves verbal memory encoding by causing a suppression of neural activity and spiking responses in the anterior temporal lobe before items to be remembered are even presented. Moreover, resection of the anterior temporal lobe caused a significant impairment in the ability of attention to improve memory encoding. Together, these findings implicate this region, the anterior temporal lobe, with a specific role in attention-enhanced memorization. We have described this work in a recent publication. We have extended this work in a separate study in which we extracted a measure of signal complexity from neural data in the temporal lobe. Signal complexity reflects the extent to which neural signals are capable of containing and conveying information. We found that increased complexity in the these neural signals was directly linked with memory performance, suggesting that cognitive functions such as memory may benefit from flexible and adaptive brain states. We have described this work in a recent publication. Finally, we have explored the use of single pulse electrical stimulation to identify stereotypical responses to stimulation in the human brain. We have developed an approach that allows us to predict the responses to novel sequences of pulses with good fidelity. We are currently preparing a manuscript describing this work for publication. In addition, we are extending this work to ask how such individual pulses can be combined across space and across time, and whether we can use the learned responses to single pulses to predict novel spatiotemporal combinations of pulses. We have developed experimental tasks to explore this question, and are currently collecting data for analyses. Finally, in a third set of studies, we have focused on understanding the interaction between the human memory and decision systems. We have previously explored the role of the basal ganglia, and specifically the subthalamic nucleus, in simple sensorimotor decisions. We recently extended this work to examine the interactions between the subthalamic nucleus and the prefrontal cortex in the context of cognitive control. We have found that cognitive control, which requires adaptations both during individual trials and adaptations across trials, involves a complex interaction of oscillatory changes in both the subthalamic nucleus and prefrontal cortex. Theta oscillations in both regions are largely involved in situations that involve conflict or stopping behavior, whereas beta oscillations in the prefrontal cortex are largely involved in adjusting responses on the next trial. We have completed this study, and a manuscript describing this work is currently in the review process. We were motivated to pursue these questions regarding simple sensorimotor decisions because we were interested in whether similar circuit dynamics are present when making non-motor decisions related to memory. In our most recent study, we focused on exploring how subjects decide to encode, and hypothesized that the decision to attend to or encode a target stimulus co-opts the same neural mechanisms used to mediate motor decisions. We found that oscillatory and spiking activity in the human subthalamic nucleus is modulated during non-motor decisions to encode items into memory or to ignore them. In addition, we have found that oscillatory communication between the subthalamic nucleus and the prefrontal cortex participates in this process. We have described this work in a recent publication. We are now currently interested in understanding how memory affects our ability to make decisions. We have developed a novel task in which participants must rely upon their memory for associations that they have formed to make decisions, and are interested in how this process is represented in the human brain. We are currently collecting data for these analyses.
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