FY2015 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 examining changes in the oscillatory power evident in these field potential signals have provided us with much insight into the changes in local population activity in the context of memory encoding and retrieval. Over the past year, however, we have largely focused our efforts on extending our analysis techniques in order to understand changes in the human brain across spatial scales. At the larger scale, we have been exploring communication between brain regions. Measures of effective connectivity attempt to identify stable pathways for communication by requiring a predictive relationship between the activity of one brain region and another. 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 demonstrated that such effective connections indeed exist in the brain, and reflect stable pathways of communication through which information is propagated. We have described these results in a manuscript that is currently in review. At the smaller scale, we have extended our ability to capture neural activity to the level of individual neuronal units from micro-electrode arrays implanted on the cortical surface in patients treated for medically refractory epilepsy. We have successfully collected single unit spiking activity from these microelectrode arrays in seven patients while they have participated in our cognitive tasks. With these additional methodological advances, we are now currently focused on three main sets of studies. In the first set of studies, we have been interested in investigating whether neuronal activity is reinstated from memory encoding to memory retrieval, and in examining the precise spatiotemporal dynamics of such reinstatement. Using a paired associates episodic memory task, we have directly examined these questions. We have previously shown that, during successful recall, there is significantly greater reinstatement of patterns of oscillatory power distributed across multiple cortical locations and across frequencies. We are currently building upon this work in two ways, using our methodological advances. First, using our metrics of effective connectivity, we have identified dynamic changes in communication between brain regions during successful memory encoding. Importantly, we have found that similar patterns of communication are present during successful retrieval, suggesting that network dynamics themselves are reinstated. We are continuing analyses of these data in anticipation of future publication. Second, we have examined the behavior of individual neurons during the paired associates task. We have found that while some neurons exhibit significant increases in firing during successful encoding while other exhibit significant decreases, when we examine the population activity of spiking neurons, we find that the same patterns of spiking activity that are present during encoding are also present during retrieval. This provides us with direct evidence that neural spiking activity in the human cortex is itself reinstated during successful retrieval. We are currently preparing a manuscript describing our work for publication. 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, and in particular the extent to which attention may mediate the formation of successful memories. We have collected data from intracranial electrodes and from our microelectrode arrays while participants engage in a behavioral task that specifically asks this question. Briefly, we present items to be encoded on a computer screen, and these items may or may not be preceded or followed by a visual cue indicating whether this item should be encoded in memory. We first found that resection of the anterior temporal lobe caused a significant drop in performance for the prospectively cued items. We next examined changes in local oscillatory activity in this region, and found significant increases in low frequency oscillatory power and significant decreases in high frequency oscillatory power in the anterior temporal lobe following the appearance of the prospective attention cue. Together, these findings implicate this region, the anterior temporal lobe, with a specific role in attention-enhanced memorization. We therefore examined neuronal mechanisms supporting this behavior by examining changes in single unit spiking activity recorded using our microelectrode arrays implanted in the anterior temporal lobe in five participants during the monitoring period. Consistent with our previous studies investigating human spiking activity, different units demonstrated different spiking behavior. Notably, however, those units that demonstrated changes in activity following the prospective cue were also likely to demonstrate similar changes following the retrospective cue, suggesting that these units may participate in a general attention mechanism used to enhance memory. We are currently preparing a manuscript describing our work for publication, and we plan to follow up on this work by examining how this region interacts with other cortical regions to prepare the brain for successful encoding. Finally, in a third set of studies, we have focused on understanding the interaction between the human memory and decision systems. It is becoming increasingly clear that the basal ganglia, with its widespread cortical connections, play a role in human decision processes. We have previously explored the role of the basal ganglia, and specifically the subthalamic nucleus, in simple sensorimotor decisions. One question, however, is whether similar circuit dynamics are present when making non-motor decisions related to memory. In our studies of attention and memory, participants actively choose to encode subsequent items based on a prospective cue. We have focused our recent efforts on exploring this process of deciding to encode, and have developed a task to explicitly test the hypothesis that the decision to attend to or encode a target stimulus co-opts the same neural mechanisms used to mediate motor decisions. We have collected data for this set of studies using our intra-operative experimental platform during deep brain stimulation surgery. Importantly, while recordingactivity from the STN duringDBS surgery, we are alsotemporarily placing subduralstrip electrodes over theprefrontal cortex (PFC). We have been motivated to simultaneously record from this region since recent studies, including our own, suggest that the PFC and STN exhibit oscillatory communication during decisions that involve conflict. We have indeed found that oscillatory communication between these structures mediates the decision to attend to and encode a memory, and is related to changes in spiking activity within the subthalamic nucleus during this non-motor task. We have completed data collection for this task and are currently preparing a manuscript for publication.
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