FY2014 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 developed and continued our work in capturing and analyzing local field potential and single unit spiking activity captured from the basal ganglia during deep brain stimulation surgery for patients with Parkinsons disease. In one set of studies, we have principally been interested in investigating whether patterns of neuronal oscillatory power are 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 first examined the changes observed in oscillatory activity during memory encoding. We then implemented analysis techniques that aggregate the distributed pattern of oscillatory power across multiple cortical locations and across multiple frequency bands in order to probe whether this activity is reinstated during recall. We have demonstrated that, during successful recall, there is significantly greater reinstatement of this pattern of oscillatory power across space and across frequencies. Furthermore, we have developed analyses that demonstrate the precise timing of such oscillatory activity and reinstatement across individual frequencies and locations. Our work examining the oscillatory changes that occur during successful memory encoding and retrieval, and the reinstatement of those changes, has recently been published. We have built upon this work in two ways. First, we have examined the functional connections that emerge between different brain areas during successful memory formation. We have found that functional connections present before the presentation of stimulus pairs predicts whether these associations will be successfully encoded. This work has recently been accepted for publication and is currently In Press. We are also interested in understanding whether the patterns of neural activity that occur during both encoding and retrieval are specific to individual items or represent a general mechanism of encoding or retrieval. To this end, we are not only examining our data collected using the paired associates task using novel analysis techniques, but we have also developed a new cognitive task specifically designed to probe this question. Our hypothesis is that information contained within the neural data may in fact predict the formation of individual associations. In a second set of studies, we have been interested in understanding how attentional mechanisms mediate the formation of successful memories. We have collected data from intracranial electrodes 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 have found that three specific brain regions modulate their neural activity depending on when this attentional cue is presented. These three regions, the prefrontal cortex, the temporoparietal junction, and the posterior temporal lobe, appear to coordinate their activity so as to encode items that are marked for attention compared to those items that lack such an attentional cue. Interestingly, the same patterns of activity that are present during an attentional cue that precedes a stimulus are also present during a separate attentional cue that follows a stimulus. These data suggest a coordinated network that mediates how attention gates memory encoding, regardless of when attention is deployed. We are preparing a manuscript describing our work for publication. In a third set of studies, we have been interested in extending our ability to capture neural activity to the level of individual neuronal units. To this end, we have devoted a significant effort to developing our ability to capture single unit spiking activity from micro-electrode arrays implanted on the cortical surface in patients treated for medically refractory epilepsy. To successfully capture such neuronal activity, we have developed our recording infrastructure to continuously capture these high-density signals both during the resting state and during our cognitive tasks. Our efforts establishing this infrastructure have found some success, and we are currently able to consistently capture these signals. We are currently in the process of collecting and analyzing these data to investigate the interaction between individual neuronal spiking and the larger local field potential signals during memory encoding and retrieval. And in a fourth set of studies, we have focused on activity in the subthalamic nucleus in order to understand the role this structure plays in mediating decision conflict as participants performed perceptual decision tasks. We have previously demonstrated that decision periods are marked by significant increases in theta oscillatory power in the subthalamic nucleus, and that these oscillations are significantly stronger during decisions that involve greater conflict. We have also shown that directed coherence between the prefrontal cortex, measured using scalp EEG, and the subthalamic nucleus is significantly higher when subjects are mediating high conflict decisions. These data suggest that theta oscillatory activity may communicate information from the cortex to the basal ganglia during decision processes. We have extended this work to investigate the role of subthalamic nucleus single-unit spiking activity and how this activity relates to the observed changes in oscillatory power. We have identified distinct neuronal populations that exhibit different temporal dynamics that are differentially mediated by conflict. Importantly, we have shown that spiking activity in these populations of neurons is entrained by theta and beta oscillations, suggesting that the cortical oscillations used to convey information regarding decision conflict to the subthalamic nucleus ultimately modulate spiking activity in that structure. Our work describing these findings has recently been accepted for publication is currently In Press. We are currently building upon these studies using two approaches. First, in addition to capturing single unit activity from deep structures within the basal ganglia, we are simultaneously measuring prefrontal cortical activity using intracranial subdural electrodes temporarily placed during DBS surgery in order to precisely understand how these structures communicate. In a new experimental design, we are specifically investigating how such communication mediates spiking activity in the subthalamic nucleus during response inhibition and during conflict. And in a second approach, in order to probe the extent to which the subthalamic nucleus is involved in general cognitive function, we are asking whether the same mechanisms that govern activity during conflict are also active during tasks that do not involve actual motor movements.
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