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Open Access Publications from the University of California

Scholarly Works (8 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2020)

Feedback processing is a key determinant of the decision-making process. During feedback processing, the outcomes of subjects’ responses are evaluated based on the outcome’s value and subjects’ expectations. These processes inform subjects’ future choices as they learn how to maximize reward and minimize punishment. Abnormalities in feedback processing are present in several psychiatric disorders, including obsessive-compulsive disorder (OCD), major depressive disorder (MDD), and substance abuse disorder (SUD).

The orbitofrontal cortex (OFC) is claimed as an important brain region in feedback processing across species. Studies in primates and rodents have mainly analyzed activities of individual neurons (single unit activity)/neuronal populations. One of the challenges in recording single unit activities is the cost of device and uncertainty of the yield and longevity of recording. In my master’s project, I have developed a single unit collection device that enables affordable collection of single unit activity in rat OFC and anterior cingulate cortex for an average of 12 weeks with a range from 5 to 24 weeks. Each device costs less than $100 U.S. dollars, and the technique can be easily applied to other superficial and deep brain regions.

Using our single unit probe design, we have collected single unit activities in OFC when rats performed a go/wait task. We have found that the activity OFC neurons were modulated during the period of reward/punishment evaluation and response preparation. Our findings are consistent with previous literature. We are in the progress of analyzing single unit activity with LFP activity through techniques such as spike-field coherence.

    Cover page: Neural Activity in Rat Orbitofrontal Cortex Related to Punishment and Reward
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2017)
    A fundamental goal of motor learning is to establish the neural patterns that produce a desired behavioral outcome. It remains unclear how and when the nervous system solves this 'credit assignment' problem. Using neuroprosthetic learning, in which we could control the causal relationship between neurons and behavior, we found that sleep-dependent processing was required for credit assignment and the establishment of task-related functional connectivity reflecting the casual neuron-behavior relationship. Notably, we observed a strong link between the microstructure of sleep reactivations and credit assignment, with downscaling of non-causal activity. Decoupling of spiking to slow oscillations using optogenetic methods eliminated rescaling. Thus, our results suggest that coordinated firing during sleep is essential for establishing sparse activation patterns that reflect the causal neuron-behavior relationship.
      Cover page: Neural reactivations during sleep determine network credit assignment
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2022)
      Sleep is known to promote recovery after stroke. Yet it remains unclear how stroke affects neural processing during sleep. Using an experimental stroke model in rats along with electrophysiological monitoring of neural firing and sleep microarchitecture, here we show that sleep processing is altered by stroke. We find that the precise coupling of spindles to global slow oscillations (SOs), a phenomenon that is known to be important for memory consolidation, is disrupted by a pathological increase in "isolated" local delta waves. The transition from this pathological to a physiological state-with increased spindle coupling to SO-is associated with sustained performance gains during recovery. Interestingly, post-injury sleep could be pushed toward a physiological state via a pharmacological reduction of tonic γ-aminobutyric acid (GABA). Together, our results suggest that sleep processing after stroke is impaired due to an increase in delta waves and that its restoration can be important for recovery.
        Cover page: Recovery of consolidation after sleep following stroke—interaction of slow waves, spindles, and GABA
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2015)

        Background

        Rodent forelimb reaching behaviors are commonly assessed using a single-pellet reach-to-grasp task. While the task is widely recognized as a very sensitive measure of distal limb function, it is also known to be very labor-intensive, both for initial training and the daily assessment of function.

        New method

        Using components developed by open-source electronics platforms, we have designed and tested a low-cost automated behavioral box to measure forelimb function in rats. Our apparatus, made primarily of acrylic, was equipped with multiple sensors to control the duration and difficulty of the task, detect reach outcomes, and dispense pellets. Our control software, developed in MATLAB, was also used to control a camera in order to capture and process video during reaches. Importantly, such processing could monitor task performance in near real-time.

        Results

        We further demonstrate that the automated apparatus can be used to expedite skill acquisition, thereby increasing throughput as well as facilitating studies of early versus late motor learning. The setup is also readily compatible with chronic electrophysiological monitoring.

        Comparison with existing methods

        Compared to a previous version of this task, our setup provides a more efficient method to train and test rodents for studies of motor learning and recovery of function after stroke. The unbiased delivery of behavioral cues and outcomes also facilitates electrophysiological studies.

        Conclusions

        In summary, our automated behavioral box will allow high-throughput and efficient monitoring of rat forelimb function in both healthy and injured animals.
          Cover page: An automated behavioral box to assess forelimb function in rats
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2007)

          Selective attention may be flexibly directed toward particular locations in the visual field (spatial attention) or to entire object configurations (object-based attention). A key question is whether spatial attention plays a direct role in the selection of objects, perhaps by spreading its facilitatory influence throughout the boundaries of an object. We studied the relationship between spatial and object-based attention in a design in which subjects attended to brief offsets of one corner of a real or illusory square form. Object-selective attention was indexed by differences in event-related potential (ERP) amplitudes and blood oxygen level-dependent (BOLD) activations to unattended corner offsets in conditions in which the objects were intact versus fragmented or absent. This design ensured that object-based attention effects were not an artifact of attention being guided by simple directional cues such as parallel lines, which may have occurred in previous studies. Both space-based and object-based attention were associated with enhanced negative ERPs (N1 component at 140 - 180 ms) that were colocalized with BOLD activations in lateral occipital cortex (LOC). These results provide physiological evidence that directing spatial attention to one part of an object (whether real or illusory) facilitates the processing of the entire object at the level of the LOC and thus contributes directly to object-based selective attention.

            Cover page: The role of spatial attention in the selection of real and illusory objects
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2019)
            A remarkable feature of motor control is the ability to coordinate movements across distinct body parts into a consistent, skilled action. To reach and grasp an object, 'gross' arm and 'fine' dexterous movements must be coordinated as a single action. How the nervous system achieves this coordination is currently unknown. One possibility is that, with training, gross and fine movements are co-optimized to produce a coordinated action; alternatively, gross and fine movements may be modularly refined to function together. To address this question, we recorded neural activity in the primary motor cortex and dorsolateral striatum during reach-to-grasp skill learning in rats. During learning, the refinement of fine and gross movements was behaviorally and neurally dissociable. Furthermore, inactivation of the primary motor cortex and dorsolateral striatum had distinct effects on skilled fine and gross movements. Our results indicate that skilled movement coordination is achieved through emergent modular neural control.
              Cover page: Emergent modular neural control drives coordinated motor actions
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2015)
              Intracortical brain-machine interfaces (BMIs) may eventually restore function in those with motor disability after stroke. However, current research into the development of intracortical BMIs has focused on subjects with largely intact cortical structures, such as those with spinal cord injury. Although the stroke perilesional cortex (PLC) has been hypothesized as a potential site for a BMI, it remains unclear whether the injured motor cortical network can support neuroprosthetic control directly. Using chronic electrophysiological recordings in a rat stroke model, we demonstrate here the PLC's capacity for neuroprosthetic control and physiological plasticity. We initially found that the perilesional network demonstrated abnormally increased slow oscillations that also modulated neural firing. Despite these striking abnormalities, neurons in the perilesional network could be modulated volitionally to learn neuroprosthetic control. The rate of learning was surprisingly similar regardless of the electrode distance from the stroke site and was not significantly different from intact animals. Moreover, neurons achieved similar task-related modulation and, as an ensemble, formed cell assemblies with learning. Such control was even achieved in animals with poor motor recovery, suggesting that neuroprosthetic control is possible even in the absence of motor recovery. Interestingly, achieving successful control also reduced locking to abnormal oscillations significantly. Our results thus suggest that, despite the disrupted connectivity in the PLC, it may serve as an effective target for neuroprosthetic control in those with poor motor recovery after stroke.
                Cover page: Robust Neuroprosthetic Control from the Stroke Perilesional Cortex
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2018)
                Recent work has highlighted the importance of transient low-frequency oscillatory (LFO; <4 Hz) activity in the healthy primary motor cortex during skilled upper-limb tasks. These brief bouts of oscillatory activity may establish the timing or sequencing of motor actions. Here, we show that LFOs track motor recovery post-stroke and can be a physiological target for neuromodulation. In rodents, we found that reach-related LFOs, as measured in both the local field potential and the related spiking activity, were diminished after stroke and that spontaneous recovery was closely correlated with their restoration in the perilesional cortex. Sensorimotor LFOs were also diminished in a human subject with chronic disability after stroke in contrast to two non-stroke subjects who demonstrated robust LFOs. Therapeutic delivery of electrical stimulation time-locked to the expected onset of LFOs was found to significantly improve skilled reaching in stroke animals. Together, our results suggest that restoration or modulation of cortical oscillatory dynamics is important for the recovery of upper-limb function and that they may serve as a novel target for clinical neuromodulation.
                  Cover page: Low-frequency cortical activity is a neuromodulatory target that tracks recovery after stroke
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