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Open Access Publications from the University of California

Scholarly Works (64 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2018)

Swift detection and remembering of salient and emotional stimuli is critical for survival and adaptive fitness. Optimal emotional processing is central to mental health, abnormalities of which are frequently present across all forms of neuropsychiatric illness including major depression, post-traumatic stress disorder, and suicide. Despite the extent of the problem, our fundamental understanding of the neural circuitry underlying emotional processing remains limited, which has hindered therapeutic advances in neuropsychiatric diseases.

Here, we employed intracranial electrodes in drug-resistant epilepsy patients undergoing pre-surgical evaluation to directly record neural signals from the amygdala, the hippocampus and the orbitofrontal cortex, a neuroanatomical circuit core to emotional processing. First, we examined oscillatory activity within the medial temporal lobe during processing of fearful faces compared to neutral landscapes. We found early engagement of the amygdala and unidirectional influence from the amygdala to the hippocampus during processing of fearful faces. In addition, we showed that such modulation is mediated through cross frequency coupling between theta/alpha (4-10Hz) oscillations and high gamma activity (70-200 Hz). Next, we investigated the oscillatory mechanisms of emotional memory and asked how emotion influences the discrimination of similar mnemonic experiences (e.g. pattern separation). We observed frequency-specific interactions between the amygdala and the hippocampus, with theta (3-7Hz) synchrony facilitating correct mnemonic discrimination and alpha (8-13Hz) synchrony promoting incorrect recognition. Finally, we examined how past context modulates our future perception of facial expression. Using Bayesian decoding techniques, we showed that the high gamma activity is precisely aligned with the phase of theta oscillations, in which the probability densities of the reconstructed time showed that the descending theta phase encodes past context and ascending theta phase represents future face perception. In sum, intracranial recordings have provided critical insights on how oscillations coordinate circuit dynamics in the frontotemporal network to rapidly and flexibly organize emotional information in humans.

    Cover page: Circuit Dynamics of Emotional Processing: Insights from Human Intracranial RecordingsCreative Commons 'BY' version 4.0 license
    • Thesis
    • Peer Reviewed
    UC Irvine Electronic Theses and Dissertations (2022)

    Remembering a salient experience and discriminating between similar events are two cognitive abilities that are critical for human adaptation and survival. They depend on optimal functioning of neurobiological mechanisms underlying episodic memory processing. Enhanced memory for emotional stimuli requires more pronounced memory encoding of emotional, relative to neutral stimuli. Discrimination between two different events depends on a neural computation of pattern separation. However, the exact neural mechanisms underlying memory encoding and pattern separation are still unclear.In the present thesis, I applied an emotional memory encoding and discrimination task in human participants and examined the neural dynamics in the medial temporal lobe, known as a critical brain structure for memory processing. Local field potentials were recorded in the amygdala, hippocampus and peri-hippocampal regions, including entorhinal, parahippocampal and perirhinal cortex, from drug-resistant epilepsy patients undergoing pre-surgical monitoring. First, I examined the role of hippocampal awake sharp-wave ripples (aSWRs) on emotional memory encoding, finding increased aSWRs after encoding of emotional, compared to neutral stimuli. The aSWRs were accompanied by memory reinstatement in the amygdala-hippocampal network. Additionally, the cross-structure joint-reinstatement during aSWR events was predictive of later memory performance. Next, I investigated the neural mechanisms of pattern separation during memory discrimination. Stimulus-specific neural representation in the hippocampus predicted memory discrimination. Moreover, I designed a machine learning algorithm to decode the neural state, and found that the neural trajectory of dentate gyrus/Cornu Ammonis3 (DG/CA3) visited more unexplored state and predicted successful pattern separation. Finally, continuously increasing dimensionality predicts correct discrimination, suggesting code expansion as a mechanism implementing the pattern separation in the DG/CA3 region. Overall, these results suggest a putative mechanism for encoding and discriminating for emotional experience.

      Cover page: Emotional Memory Processing and Pattern Separation in Medial Temporal Lobe
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2022)
      Context shapes our perception of facial expressions during everyday social interactions. We interpret a person's face in a hostile situation negatively and judge the same face under pleasant circumstances positively. Critical to our adaptive fitness, context provides situation-specific framing to resolve ambiguity and guide our interpersonal behavior. This context-specific modulation of facial expression is thought to engage the amygdala, hippocampus, and orbitofrontal cortex; however, the underlying neural computations remain unknown. Here we use human intracranial electroencephalograms (EEGs) directly recorded from these regions and report bidirectional theta-gamma interactions within the amygdala-hippocampal network, facilitating contextual processing. Contextual information is subsequently represented in the orbitofrontal cortex, where a theta phase shift binds context and face associations within theta cycles, endowing faces with contextual meanings at behavioral timescales. Our results identify theta phase shifts as mediating associations between context and face processing, supporting flexible social behavior.
        Cover page: Neural computations underlying contextual processing in humans
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2017)
        The response to an upcoming salient event is accelerated when the event is expected given the preceding events - i.e. a temporal context effect. For example, naming a picture following a strongly constraining temporal context is faster than naming a picture after a weakly constraining temporal context. We used sentences as naturalistic stimuli to manipulate expectations on upcoming pictures without prior training. Here, using intracranial recordings from the human hippocampus we found more power in the high-frequency band prior to high-expected pictures than weakly expected ones. We applied pattern similarity analysis on the temporal pattern of hippocampal high-frequency band activity in single hippocampal contacts. We found that greater similarity in the pattern of hippocampal field potentials between pre-picture interval and expected picture interval in the high-frequency band predicted picture-naming latencies. Additional pattern similarity analysis indicated that the hippocampal representations follow a semantic map. The results suggest that hippocampal pre-activation of expected stimuli is a facilitating mechanism underlying the powerful contextual behavioral effect.
          Cover page: Human hippocampal pre-activation predicts behavior
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2019)
          Two primary functions attributed to the hippocampus and prefrontal cortex (PFC) network are retaining the temporal and spatial associations of events and detecting deviant events. It is unclear, however, how these two functions converge into one mechanism. Here, we tested whether increased activity with perceiving salient events is a deviant detection signal or contains information about the event associations by reflecting the magnitude of deviance (i.e., event saliency). We also tested how the deviant detection signal is affected by the degree of anticipation. We studied regional neural activity when people watched a movie that had varying saliency of a novel or an anticipated flow of salient events. Using intracranial electroencephalography from 10 patients, we observed that high-frequency activity (50-150 Hz) in the hippocampus, dorsolateral PFC, and medial OFC tracked event saliency. We also observed that medial OFC activity was stronger when the salient events were anticipated than when they were novel. These results suggest that dorsolateral PFC and medial OFC, as well as the hippocampus, signify the saliency magnitude of events, reflecting the hierarchical structure of event associations.
            Cover page: Medial Orbitofrontal Cortex, Dorsolateral Prefrontal Cortex, and Hippocampus Differentially Represent the Event Saliency
            • Article
            • Peer Reviewed
            UC Irvine Previously Published Works (2020)

            Objective

            High-frequency oscillations (HFOs) are a promising biomarker for the epileptogenic zone. However, no physiological definition of an HFO has been established, so detection relies on the empirical definition of an HFO derived from visual observation. This can bias estimates of HFO features such as amplitude and duration, thereby hindering their utility as biomarkers. Therefore, we set out to develop an algorithm that detects high-frequency events in the intracranial EEG that are morphologically distinct from background without requiring assumptions about event amplitude or shape.

            Method

            We propose the anomaly detection algorithm (ADA), which uses unsupervised machine learning to identify segments of data that are distinct from the background. We apply ADA and a standard HFO detector using a root mean square amplitude threshold to intracranial EEG from 11 patients undergoing evaluation for epilepsy surgery. The rate, amplitude, and duration of the detected events and the percent overlap between the two detectors are compared.

            Result

            In the seizure onset zone (SOZ), ADA detected a subset of conventional HFOs. In non-SOZ channels, ADA detected at least twice as many events as the standard approach, including some conventional HFOs; however, ADA also identified many low and intermediate amplitude events missed by the standard amplitude-based method. The rate of ADA events was similar across all channels; however, the amplitude of ADA events was significantly higher in SOZ channels (P < .0045), and the amplitude measurement was more stable over time than the HFO rate, as indicated by a lower coefficient of variation (P < .0125).

            Significance

            ADA does not require human supervision, parameter optimization, or prior assumptions about event shape, amplitude, or duration. Our results suggest that the algorithm's estimate of event amplitude may differentiate SOZ and non-SOZ channels. Further studies will examine the utility of HFO amplitude as a biomarker for epilepsy surgical outcome.
              Cover page: Detection of anomalous high‐frequency events in human intracranial EEG
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2023)
              We report distinct contributions of multiple memory systems to the retrieval of the temporal order of events. The neural dynamics related to the retrieval of movie scenes revealed that recalling the temporal order of close events elevates hippocampal theta power, like that observed for recalling close spatial relationships. In contrast, recalling far events increases beta power in the orbitofrontal cortex, reflecting recall based on the overall movie structure.
                Cover page: Multiple memory systems for efficient temporal order memory.
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2011)
                This study tested the hypothesis that executive dysfunction, common in temporal lobe epilepsy (TLE), is associated with an abnormal frontostriatal network. Structural and diffusion tensor MR scans, the Wisconsin Card Sorting Test (WCST) targeting cognitive flexibility, and the Trail Making Test B examining parallel sequencing were obtained from 9 patients with left TLE and 17 healthy controls. The five major findings were: (1) Caudate volume is reduced on the left side in TLE. (2) The atrophy involves the dorsal and ventral head of the caudate. (3) These atrophic caudate regions have a corresponding high probability of connections to dorsal prefrontal, anterior cingulate, and orbitofrontal cortex. (4) Smaller caudate volumes are linked to greater numbers of WCST perseverative errors. (5) Reduced connections between caudate and dorsal prefrontal cortex correlated with poorer scores on the Trail Making Test B. The results suggest that atrophy in the dorsal head of the caudate might disrupt frontostriatal networks that are critical for executive functioning in TLE.
                  Cover page: Caudate atrophy and impaired frontostriatal connections are linked to executive dysfunction in temporal lobe epilepsyCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2023)
                  Context modulates sensory neural activations enhancing perceptual and behavioral performance and reducing prediction errors. However, the mechanism of when and where these high-level expectations act on sensory processing is unclear. Here, we isolate the effect of expectation absent of any auditory evoked activity by assessing the response to omitted expected sounds. Electrocorticographic signals were recorded directly from subdural electrode grids placed over the superior temporal gyrus (STG). Subjects listened to a predictable sequence of syllables, with some infrequently omitted. We found high-frequency band activity (HFA, 70-170 Hz) in response to omissions, which overlapped with a posterior subset of auditory-active electrodes in STG. Heard syllables could be distinguishable reliably from STG, but not the identity of the omitted stimulus. Both omission- and target-detection responses were also observed in the prefrontal cortex. We propose that the posterior STG is central for implementing predictions in the auditory environment. HFA omission responses in this region appear to index mismatch-signaling or salience detection processes.
                    Cover page: Unexpected sound omissions are signaled in human posterior superior temporal gyrus: an intracranial study.
                    • Article
                    • Peer Reviewed
                    ICTS Publications (2015)
                      Cover page: Altered organization of face-processing networks in temporal lobe epilepsyCreative Commons 'BY' version 4.0 license
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