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  1. Article: Coupling of saccade plans to endogenous attention during urgent choices.

    Goldstein, Allison T / Stanford, Terrence R / Salinas, Emilio

    bioRxiv : the preprint server for biology

    2024  

    Abstract: The neural mechanisms that willfully direct attention to specific locations in space are closely related to those for generating targeting eye movements (saccades). However, the degree to which the voluntary deployment of attention to a location is ... ...

    Abstract The neural mechanisms that willfully direct attention to specific locations in space are closely related to those for generating targeting eye movements (saccades). However, the degree to which the voluntary deployment of attention to a location is necessarily accompanied by a corresponding saccade plan remains unclear. One problem is that attention and saccades are both automatically driven by salient sensory events; another is that the underlying processes unfold within tens of milliseconds only. Here, we use an urgent task design to resolve the evolution of a visuomotor choice on a moment-by-moment basis while independently controlling the endogenous (goal-driven) and exogenous (salience-driven) contributions to performance. Human participants saw a peripheral cue and, depending on its color, either looked at it (prosaccade) or looked at a diametrically opposite, uninformative non-cue (antisaccade). By varying the luminance of the stimuli, the exogenous contributions could be cleanly dissociated from the endogenous process guiding the choice over time. According to the measured timecourses, generating a correct antisaccade requires about 30 ms more processing time than generating a correct prosaccade based on the same perceptual signal. The results indicate that saccade plans are biased toward the location where attention is endogenously deployed, but the coupling is weak and can be willfully overridden very rapidly.
    Language English
    Publishing date 2024-03-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.01.583058
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Alcohol withdrawal produces changes in excitability, population discharge probability, and seizure threshold.

    Alberto, Gregory E / Klorig, David C / Goldstein, Allison T / Godwin, Dwayne W

    Alcohol, clinical & experimental research

    2023  Volume 47, Issue 2, Page(s) 211–218

    Abstract: Background: Alcohol withdrawal syndrome (AWS) results from the sudden cessation of chronic alcohol use and is associated with high morbidity and mortality. Alcohol withdrawal-induced central nervous system (CNS) hyperexcitability results from complex, ... ...

    Abstract Background: Alcohol withdrawal syndrome (AWS) results from the sudden cessation of chronic alcohol use and is associated with high morbidity and mortality. Alcohol withdrawal-induced central nervous system (CNS) hyperexcitability results from complex, compensatory changes in synaptic efficacy and intrinsic excitability. These changes in excitability counteract the depressing effects of chronic ethanol on neural transmission and underlie symptoms of AWS, which range from mild anxiety to seizures and death. The development of targeted pharmacotherapies for treating AWS has been slow, due in part to the lack of available animal models that capture the key features of human AWS. Using a unique optogenetic method of probing network excitability, we examined electrophysiologic correlates of hyperexcitability sensitive to early changes in CNS excitability. This method is sensitive to pharmacologic treatments that reduce excitability and may represent a platform for AWS drug development.
    Methods: We applied a newly developed method, the optogenetic population discharge threshold (oPDT), which uses light intensity response curves to measure network excitability in chronically implanted mice. Excitability was tracked using the oPDT before, during, and after the chronic intermittent exposure (CIE) model of alcohol withdrawal (WD).
    Results: Alcohol withdrawal produced a dose-dependent leftward shift in the oPDT curve (denoting increased excitability), which was detectable in as few as three exposure cycles. This shift in excitability mirrored an increase in the number of spontaneous interictal spikes during withdrawal. In addition, Withdrawal lowered seizure thresholds and increased seizure severity in optogenetically kindled mice.
    Conclusion: We demonstrate that the oPDT provides a sensitive measure of alcohol withdrawal-induced hyperexcitability. The ability to actively probe the progression of excitability without eliciting potentially confounding seizures promises to be a useful tool in the preclinical development of next-generation pharmacotherapies for AWS.
    MeSH term(s) Humans ; Mice ; Animals ; Substance Withdrawal Syndrome/complications ; Alcoholism/complications ; Patient Discharge ; Ethanol/adverse effects ; Seizures/chemically induced ; Alcohol Withdrawal Seizures/complications
    Chemical Substances Ethanol (3K9958V90M)
    Language English
    Publishing date 2023-01-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2993-7175
    ISSN (online) 2993-7175
    DOI 10.1111/acer.15004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Exogenous capture accounts for fundamental differences between pro- and antisaccade performance.

    Goldstein, Allison T / Stanford, Terrence R / Salinas, Emilio

    eLife

    2022  Volume 11

    Abstract: To generate the next eye movement, oculomotor circuits take into consideration the physical salience of objects in view and current behavioral goals, exogenous and endogenous influences, respectively. However, the interactions between exogenous and ... ...

    Abstract To generate the next eye movement, oculomotor circuits take into consideration the physical salience of objects in view and current behavioral goals, exogenous and endogenous influences, respectively. However, the interactions between exogenous and endogenous mechanisms and their dynamic contributions to target selection have been difficult to resolve because they evolve extremely rapidly. In a recent study (Salinas et al., 2019), we achieved the necessary temporal precision using an urgent variant of the antisaccade task wherein motor plans are initiated early and choice accuracy depends sharply on when exactly the visual cue information becomes available. Empirical and modeling results indicated that the exogenous signal arrives ∼80 ms after cue onset and rapidly accelerates the (incorrect) plan toward the cue, whereas the informed endogenous signal arrives ∼25 ms later to favor the (correct) plan away from the cue. Here, we scrutinize a key mechanistic hypothesis about this dynamic, that the exogenous and endogenous signals act at different times and independently of each other. We test quantitative model predictions by comparing the performance of human participants instructed to look toward a visual cue or away from it under high urgency. We find that, indeed, the exogenous response is largely impervious to task instructions; it simply flips its sign relative to the correct choice, and this largely explains the drastic differences in psychometric performance between the two tasks. Thus, saccadic choices are strongly dictated by the alignment between salience and behavioral goals.
    MeSH term(s) Eye Movements ; Humans ; Photic Stimulation ; Psychomotor Performance/physiology ; Reaction Time/physiology ; Saccades
    Language English
    Publishing date 2022-07-27
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.76964
    Database MEDical Literature Analysis and Retrieval System OnLINE

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