Investigating the neural mechanisms of human cognitive function through intracranial recordings

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications & trials

Abstract

FY2021 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 drug resistant epilepsy receiving intracranial electrodes and surgical treatment at the Clinical Center have been recruited for these studies. Our work takes advantage of the opportunities to record both intracranial EEG and single unit spiking activity from these implanted electrodes as participants perform a variety of cognitive tasks during the monitoring period. Our efforts are focused on understanding changes in human brain activity across these different spatial scales. In order to properly interpret how such changes in neural activity may underlie our ability to form and retrieve memories, an important goal for our lab has been to understand how brain regions represent information and how they communicate with one another across spatial scales. One recent phenomenon that we have identified in our neural recordings is the presence of discrete high frequency oscillations known as ripples. We have focused some of our recent work on understanding how these ripples are coordinated across spatial scales and how they relate to underlying spiking activity. We have found that synchronized bursts of spiking activity together contribute to the emergence of ripple oscillations at the local field potential level, and that coordinated ripples across multiple micro-electrodes together contribute to the ripples observed at the largest spatial scale in the iEEG recordings. We have recently completed a manuscript describing this work (Tong AP, Vaz A, Wittig JH, Inati SK, Zaghloul KA (2021) In Revision). In a related effort, we have continued our work examining traveling waves of low frequency activity at both the larger spatial scale and at the smaller micro-scale. These waves coordinate underlying spiking activity and may be relevant for the ability to move information across the brain. We have completed a manuscript describing this work that we have submitted for publication (Sreekumar V, Wittig JH, Inati SK, Zaghloul KA (2021) Traveling waves at the macro and micro scale in the human brain, In Review). In order to probe how memories are formed and retrieved in the brain, we have also focused our efforts on understanding how information is represented in the neural signals that we record. To this end, we have explored how connectivity at the smallest spatial scales may provide insights into the functional organization and structure of the human cortex, and how such organization may be relevant for encoding information. Specifically, we have found that small local patches of cortex, which we refer to as modules, are highly connected and that activity within these modules is differentially modulated by different stimuli, suggesting that these modules encode different functional information. We have completed this work and this manuscript has been recently submitted for publication (Chapeton JI, Wittig JH, Inati SK, Zaghloul KA (2020) In Review). In addition, we have previously demonstrated that successful memory retrieval is associated with ripples, which in turn are accompanied by underlying bursts of neuronal spiking that occur in a specific temporal order. Critically, we found that the order of firing is specific to the individual item that is being studied and recall. We have now been examining this phenomenon in greater detail. Specifically, we have found preliminary evidence that the specific order of neuronal firing in the anterior temporal lobe can distinguish different semantic categories, and therefore temporal order of neural activity seems to play a role in representing different semantic information. We are currently preparing this work for submission (Wittig JH, Vaz AP, Inati SK, Zaghloul KA (2020) In Preparation). In a separate set of studies, we have focused on understanding the interaction between the human memory and decision systems and how memory may be used for future cognitive behavior. In a study just completed, we examined the hypothesis that recent episodes that we experience can be used to construct an internal model of the world that we then use to predict future events. We presented our participants with images of natural scenes that they had previously seen, but we manipulated some of the images by adding or removing an item from each image. We found that when individuals successfully identify this manipulation, we observe a prediction error signal that first emerges in regions of higher order visual cortex and that then propagates to the medial temporal lobe. Our data therefore suggest that even a single exposure to an event or episode is sufficient to establish a representation of a memory of that event in cortical regions that can be used for subsequent comparisons. We recently published our manuscript detailing these efforts (Haque RU, Inati SK, Levey AI, Zaghloul KA (2020) Nature Communications). In a related study, we have also been examining how memories formed in different contexts can affect our ability to make decisions in the future. For this study, we developed a new behavioral task in which individuals learn that certain items are more rewarding than others, but only in particular contexts (e.g. in a scene of a forest, or of a beach). Later, we then virtually place the individuals within these different contexts and ask them to make the appropriate decision based on the memories they have formed of the correct reward contingencies. We have been fortunate to capture these data from both our epilepsy patients, allowing us to capture recordings from the cortex and medial temporal lobe, as well as separately from patients receiving deep brain stimulation surgery, giving us the opportunity to also examine neural activity in the basal ganglia. Our preliminary data suggest that the subthalamic nucleus is involved in these memory guided decisions, and that correctly making a choice involves coordinated activity between the medial temporal lobe and prefrontal cortex. We are currently preparing a manuscript describing these findings for submission (Tong AP, Sreekumar V, Inati SK, Zaghloul KA (2021) In Preparation). Finally, we have recently developed an interest in the intersection between long term and short term memory. As one of the cornerstones of human cognition, short-term (or working) memory (STM) plays a fundamental role in various perceptual and cognitive functions, including fluid intelligence. STM, however, is notoriously limited both in the amount, or capacity, and the precision of information that one can retain over a brief retention interval. Notably, there are significant parallels between the computations required for STM precision and those required to minimize mnemonic interference for long-term memory, a process referred to as pattern separation that has traditionally been ascribed to the medial temporal lobe (MTL). Yet despite these computational parallels, many influential theories and decades of empirical findings have suggested a clear delineation in the computational and anatomical substrates underlying the two types of memory. We have recently uncovered direct evidence supporting an alternative hypothesis, that the circuitry of the MTL, long viewed as a dedicated module for distinguishing similar neural representations of information in long-term memory, also supports STM precision. We have completed this work and a manuscript describing this work has been recently submitted for publication (Xie W, Cappiello M, Wittig JH, Bhasin S, Zawora C, Yassa MA, Ester E, Inati SK, Zaghloul KA, Zhang W (2021) In Review).