Using Mouse-tracking to Examine the Time Course of Long-term Repetition-Priming

IntroductionThe long-term safety and efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention deficit/hyperactivity disorder (ADHD) was evaluated in a European 2-year, open-label study (SPD489-404).ObjectiveTo evaluate the time-course of treatment-emergent adverse events (TEAEs) in SPD489-404.MethodsParticipants aged 6–17 years received open-label LDX (30, 50 or 70 mg/day) for 104 weeks (4 weeks dose-optimization; 100 weeks dose-maintenance).ResultsAll enrolled participants (n = 314) were included in the safety population and 191 (60.8%) completed the study. TEAEs occurred in 282 (89.8%) participants; most were mild or moderate. TEAEs considered by the investigators as related to LDX were reported by 232 (73.9%) participants with the following reported for ≥ 10% of participants: decreased appetite (49.4%), weight decreased (18.2%), insomnia (13.1%). TEAEs leading to discontinuation and serious TEAEs occurred in 39 (12.4%) and 28 (8.9%) participants, respectively. The median (range) time to first onset and duration, respectively, of TEAEs identified by the sponsor as being of special interest were: insomnia (insomnia, initial insomnia, middle insomnia, terminal insomnia), 17.0 (1–729) and 42.8 (1–739) days; weight decreased, 29.0 (1–677) and 225.0 (26–724) days; decreased appetite, 13.5 (1–653) and 169.0 (1–749) days; headache, 22.0 (1–718) and 2.0 (1–729) days. Reports of insomnia, weight decreased, decreased appetite and headache were highest in the first 4–12 weeks.ConclusionsTEAEs associated with long-term LDX treatment were characteristic of stimulant medications, with the greatest incidence observed during the first 4–12 weeks.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Time Course of Expression of “Early” Genes during Long-Term Posttetanic Potentiation in Rat Hippocampal CA1 Field

Bulletin of Experimental Biology and Medicine ◽

10.1007/s10517-010-0726-5 ◽

2009 ◽

Vol 148 (3) ◽

pp. 416-418 ◽

Cited By ~ 3

Author(s):

O. O. Sokolova ◽

M. B. Shtark ◽

P. D. Lisachev ◽

V. O. Pustyl’nyak ◽

I. V. Pan

Keyword(s):

Time Course ◽

Posttetanic Potentiation ◽

Early Genes ◽

Hippocampal Ca1 ◽

Hippocampal Ca1 Field

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Central Insulin Signaling Is Attenuated by Long-Term Insulin Exposure via Insulin Receptor Substrate-1 Serine Phosphorylation, Proteasomal Degradation, and Lysosomal Insulin Receptor Degradation

Endocrinology ◽

10.1210/en.2009-0838 ◽

2010 ◽

Vol 151 (1) ◽

pp. 75-84 ◽

Cited By ~ 38

Author(s):

Christopher M. Mayer ◽

Denise D. Belsham

Keyword(s):

Insulin Resistance ◽

Insulin Receptor ◽

Insulin Signaling ◽

Time Course ◽

Proteasomal Degradation ◽

Serine Phosphorylation ◽

Neuronal Function ◽

Protein Levels ◽

Phosphorylated Akt

Abstract Central insulin signaling is critical for the prevention of insulin resistance. Hyperinsulinemia contributes to insulin resistance, but it is not yet clear whether neurons are subject to cellular insulin resistance. We used an immortalized, hypothalamic, clonal cell line, mHypoE-46, which exemplifies neuronal function and expresses the components of the insulin signaling pathway, to determine how hyperinsulinemia modifies neuronal function. Western blot analysis indicated that prolonged insulin treatment of mHypoE-46 cells attenuated insulin signaling through phospho-Akt. To understand the mechanisms involved, time-course analysis was performed. Insulin exposure for 4 and 8 h phosphorylated Akt and p70-S6 kinase (S6K1), whereas 8 and 24 h treatment decreased insulin receptor (IR) and IR substrate 1 (IRS-1) protein levels. Insulin phosphorylation of S6K1 correlated with IRS-1 ser1101 phosphorylation and the mTOR-S6K1 pathway inhibitor rapamycin prevented IRS-1 serine phosphorylation. The proteasomal inhibitor epoxomicin and the lysosomal pathway inhibitor 3-methyladenine prevented the degradation of IRS-1 and IR by insulin, respectively, and pretreatment with rapamycin, epoxomicin, or 3-methyladenine prevented attenuation of insulin signaling by long-term insulin exposure. Thus, a sustained elevation of insulin levels diminishes neuronal insulin signaling through mTOR-S6K1-mediated IRS-1 serine phosphorylation, proteasomal degradation of IRS-1 and lysosomal degradation of the IR.

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Auditory Long term Memory: Repetition Priming of Voice Recognition

The Quarterly Journal of Experimental Psychology Section A ◽

10.1080/713755724 ◽

1997 ◽

Vol 50 (3) ◽

pp. 498-517 ◽

Cited By ~ 32

Author(s):

Stefan R. Schweinberger ◽

Anja Herholz ◽

Volker Stief

Keyword(s):

Repetition Priming ◽

Priming Effect ◽

Voice Recognition ◽

Reaction Times ◽

Long Term Memory ◽

Term Memory ◽

Person Recognition ◽

Perceptual Representations

Two experiments examined repetition priming in the recognition of famous voices. In Experiment 1, reaction times for fame decisions to famous voice samples were shorter than in an unprimed condition, when voices were primed by a different voice sample of the same person having been presented in an earlier phase of the experiment. No effect of voice repetition was observed for non-famous voices. In Experiment 2, it was investigated whether this priming effect is voice-specific or whether it is related to post-perceptual processes in person recognition. Recognizing a famous voice was again primed by having earlier heard a different voice sample of that person. Although an earlier exposure to that person's name did not cause any priming, there was some indication of priming following an earlier exposure to that person's face. Finally, earlier exposure to the identical voice sample (as compared to a different voice sample from the same person) caused a considerable bias towards responding “famous”—i.e. performance benefits for famous but costs for nonfamous voices. The findings suggest that (1) repetition priming invoice recognition primarily involves the activation of perceptual representations of voices, and (2) it is important to determine the conditions in which priming causes bias effects that need to be disentangled from performance benefits.

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Anticipatory saccades in sequential procedural learning in monkeys

Journal of Neurophysiology ◽

10.1152/jn.1996.76.2.1361 ◽

1996 ◽

Vol 76 (2) ◽

pp. 1361-1366 ◽

Cited By ~ 41

Author(s):

K. Miyashita ◽

M. K. Rand ◽

S. Miyachi ◽

O. Hikosaka

Keyword(s):

Time Course ◽

Preceding Paper ◽

Button Press ◽

Visually Guided ◽

Short Term ◽

Skilled Performance ◽

Opposite Hand ◽

Sequential Procedures ◽

Correct Target

1. In a preceding paper we examined the short-term and long-term processes of learning of sequential procedures in monkeys. We now report that the pattern of eye movements changed along with the long-term learning. 2. The monkey's task was to press five consecutive pairs of target buttons (indicated by illumination) in the correct order for every pair, which the monkey had to find by trial and error (2 x 5 task). The whole sequence was called the "hyperset"; each pair was called the "set." 3. Initially, the saccade toward the correct target occurred after illumination of the targets (visually guided saccade). After sufficient learning, the saccade tended to occur before the target illumination (anticipatory saccade). This was true only for the hyperset that had been learned. 4. The likelihood of anticipatory saccade increased gradually over 20-30 days of practice of the particular hyperset. The time course was similar to how the hand learned (button press latency). 5. The monkeys were required to use the same hand for each hyperset throughout learning, except when we asked them to use the opposite hand. The nearly perfect performance due to the extensive practice was then deteriorated by the use of the opposite hand. We found, in addition, that anticipatory saccades became much less frequent. This finding suggests that critical for the skilled performance was the combination of the eyes and the side of the hand that was used for the practice of a given sequence.

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Static and dynamic postural control in long-term microgravity: evidence of a dual adaptation

Journal of Applied Physiology ◽

10.1152/jappl.2001.90.1.205 ◽

2001 ◽

Vol 90 (1) ◽

pp. 205-215 ◽

Cited By ~ 24

Author(s):

Guido Baroni ◽

Alessandra Pedrocchi ◽

Giancarlo Ferrigno ◽

Jean Massion ◽

Antonio Pedotti

Keyword(s):

Postural Control ◽

Time Course ◽

Center Of Mass ◽

Three Dimensional ◽

Principal Component ◽

Movement Analysis ◽

Trunk Flexion ◽

Dynamic Movement ◽

Static Body

The adaptation of dynamic movement-posture coordination during forward trunk bending was investigated in long-term weightlessness. Three-dimensional movement analysis was carried out in two astronauts during a 4-mo microgravity exposure. The principal component analysis was applied to joint-angle kinematics for the assessment of angular synergies. The anteroposterior center of mass (CM) displacement accompanying trunk flexion was also quantified. The results reveal that subjects kept typically terrestrial strategies of movement-posture coordination. The temporary disruption of joint-angular synergies observed at subjects' first in-flight session was promptly recovered when repetitive sessions in flight were analyzed. The CM anteroposterior shift was consistently <3–4 cm, suggesting that subjects could dynamically control the CM position throughout the whole flight. This is in contrast to the observed profound microgravity-induced disruption of the quasi-static body orientation and initial CM positioning. Although this study was based on only two subjects, evidence is provided that static and dynamic postural control might be under two separate mechanisms, adapting with their specific time course to the constraints of microgravity.

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The Action Dynamics of Approach-Avoidance Conflict in Decision-Making: A mouse-tracking study

10.31234/osf.io/4658p ◽

2019 ◽

Author(s):

Santiago Garcia-Guerrero ◽

Denis O'Hora ◽

Arkady Zgonnikov ◽

Stefan Scherbaum

Keyword(s):

Time Course ◽

Mouse Tracking ◽

Approach And Avoidance ◽

Response Options ◽

Shortest Route ◽

Dynamic Resolution ◽

Action Dynamics ◽

Aversive Consequence ◽

Approach Avoidance ◽

Continuous Dynamic

Approach-avoidance conflict is observed in the competing motivations towards the benefits and away from the costs of a decision. The current study employs the action dynamics of response motion, via mouse-tracking, in an attempt to characterize the continuous dynamic resolution of such conflicts. Approach-avoidance conflict (AAC) was generated by varying the appetitive consequences of a decision (i.e., point rewards and shorter participation time) in the presence of a simultaneous aversive consequence (i.e., shock probability). In two experiments, we found that AAC differentially affected response trajectories. Overall, approach trajectories were less complex than avoidance trajectories. As approach and avoidance motivations neared equipotentiality, response trajectories were more deflected from the shortest route to the eventual choice. Consistency in the location of approach and avoidance response options reduced variability in performance enabling more sensitive estimates of dynamic conflict. The time course of competing influences on response trajectories including trial-to-trial effects and conflict between approach and avoidance were estimated using regression analyses. We discuss these findings in terms of a dynamic theory of approach-avoidance that we hope will lead to insights of practical relevance in the field of maladaptive avoidance.

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