Methylphenidate does not enhance visual working memory but benefits motivation in macaque monkeys

Oemisch, Mariann; Johnston, Kevin; Paré, Martin

doi:10.1016/j.neuropharm.2016.06.019

Cited by 11 publications

(15 citation statements)

References 127 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We used between 2-6 mg/kg (see Methods; Kodama et al, 2017;Oemisch et al, 2016;Rajala et al, 2012;2020), and the data from all dosages were included together in the analyses to avoid best dose analyses (Soto et al, 2013; while our goal was to use the systemic administration of methylphenidate as a causal test of our hypotheses, not to test for dosedependent effects, we have included analyses per dosage in the Supplementary Figures).…”

Section: Resultsmentioning

confidence: 99%

“…Methylphenidate was administered on alternating data collection days (these did not include days on which data were not collected or days on which an insufficient number of trials were collected -see Data analysis) for several weeks, providing a minimum of a 24-hour washout period following drug administration prior to collecting control day data (Kodama et al, 2017). A 24-hour washout period between drug and control days was selected based on measurements of orally administered methylphenidate plasma concentrations in rhesus monkeys that determined the drug's half-life to be less than two hours (Doerge et al, 2000), such that it is undetectable after 12 hours (Oemisch et al, 2016).…”

Section: Methylphenidate Administrationmentioning

confidence: 99%

See 1 more Smart Citation

Methylphenidate as a causal test of translational and basic neural coding hypotheses

Bowes

Ruff

et al. 2021

Preprint

View full text Add to dashboard Cite

Most systems neuroscience studies fall into one of two categories: basic science work aimed at understanding the relationship between neurons and behavior, or translational work aimed at developing treatments for neuropsychiatric disorders. Here we use these two approaches to inform and enhance each other. Our study both tests hypotheses about basic science neural coding principles and elucidates the neuronal mechanisms underlying new, clinically relevant behavioral effects of systemically administered methylphenidate (Ritalin). We discovered that orally administered methylphenidate, used clinically to treat Attention Deficit Hyperactivity Disorder (ADHD) and generally to enhance cognition (Lakhan & Kirchgessner, 2012; Maher, 2008), increases spatially selective visual attention, enhancing visual performance at only the attended location. And as predicted by our previous work (Ni et al., 2018), we found that this causal manipulation enhances vision in rhesus macaques specifically when it decreases the mean correlated variability of neurons in visual area V4. Our findings demonstrate that the visual system is a platform for understanding the neural underpinnings of both complex cognitive processes (basic science) and neuropsychiatric disorders (translation). Addressing basic science hypotheses, our results are consistent with a scenario in which methylphenidate has cognitively specific effects by working through naturally selective cognitive mechanisms. Clinically, our findings suggest that the often staggeringly specific symptoms of neuropsychiatric disorders may be caused and treated by leveraging general mechanisms.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methylphenidate Administrationmentioning

confidence: 99%

Methylphenidate as a causal test of translational and basic neural coding hypotheses

Bowes

Ruff

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Finally, because the target stimuli were equidistant in our simulations (per Heyselaar et al 2011;Oemisch et al 2016) but were nonequidistant in some of the experiments providing the data to which we compare model performance (e.g., Bays et al 2009;Luck and Vogel 1997;Zhang and Luck 2008), we ran additional simulations to test the robustness of our results to nonequidistant target stimuli. In these simulations (with the default configuration) we placed the stimuli adjacent to one another on the 2-item, 3-item, and 4-item memory tasks, using the spacing of the 5-item task (72°apart; Fig.…”

Section: Broad Feedback Inhibition Underlies Slot-like Capacity and Resource-like Codingmentioning

confidence: 99%

Slot-like capacity and resource-like coding in a neural model of multiple-item working memory

Standage

Paré

2018

Journal of Neurophysiology

Self Cite

View full text Add to dashboard Cite

For the past decade, research on the storage limitations of working memory has been dominated by two fundamentally different hypotheses. On the one hand, the contents of working memory may be stored in a limited number of "slots," each with a fixed resolution. On the other hand, any number of items may be stored but with decreasing resolution. These two hypotheses have been invaluable in characterizing the computational structure of working memory, but neither provides a complete account of the available experimental data or speaks to the neural basis of the limitations it characterizes. To address these shortcomings, we simulated a multiple-item working memory task with a cortical network model, the cellular resolution of which allowed us to quantify the coding fidelity of memoranda as a function of memory load, as measured by the discriminability, regularity, and reliability of simulated neural spiking. Our simulations account for a wealth of neural and behavioral data from human and nonhuman primate studies, and they demonstrate that feedback inhibition lowers both capacity and coding fidelity. Because the strength of inhibition scales with the number of items stored by the network, increasing this number progressively lowers fidelity until capacity is reached. Crucially, the model makes specific, testable predictions for neural activity on multiple-item working memory tasks. NEW & NOTEWORTHY Working memory is the ability to keep information in mind and is fundamental to cognition. It is actively debated whether the storage limitations of working memory reflect a small number of storage units (slots) or a decrease in coding resolution as a limited resource is allocated to more items. In a cortical model, we found that slot-like capacity and resource-like neural coding resulted from the same mechanism, offering an integrated explanation for storage limitations.

show abstract

“…3 Several studies failed to find an effect of psychostimulants greater than a placebo effect, 7 and although pooled effect sizes point to a possible benefit, even these are currently inconclusive. 8 Given evidence that psychostimulants increase motivation and interest, [9][10][11] the effects of psychostimulants on fatigue may be mediated by increasing motivation. Failure to enroll patients with low motivation would mean excluding patients who would potentially experience the greatest benefit of psychostimulants.…”

Section: Introductionmentioning

confidence: 99%

A central role for apathy in the effectiveness of interventions for cancer‐related fatigue

et al. 2020

View full text Add to dashboard Cite

Objective: Cancer-related fatigue (CRF) affects a substantial number of cancer patients and survivors. Recommendations for CRF treatments are largely based on results of randomized controlled trials. The interpretability of such results is limited to patients eligible and willing to participate in these trials. We aimed to address this limitation in a retrospective study of patients seen at a CRF clinic in a comprehensive cancer center. The objectives were to (a) determine the effectiveness of clinician-initiated interventions for CRF and identify their mediators and (b) describe the frequency and effectiveness of patient-initiated physical activity (PA) behavior for alleviating CRF and identify determinants of this PA. Methods: Data (patient-reported somatic and mood symptoms; clinical data; clinician-documented changes in medication and behavior) from n = 213 patients collected as part of the clinic's standard of care at initial clinical consult and follow-up 4 to 11 weeks later were included. Effects of clinician-initiated interventions and patient-initiated PA on change in fatigue were analyzed using linear models. Results: Of all clinician-initiated interventions, only psychostimulant start was recorded frequent enough for further investigation and was associated with reduced fatigue; this association was mediated by a reduction in apathy. PA was also associated with reduced fatigue severity. PA initiation/increase after consult was associated with lower apathy at consult. Conclusions: These results demonstrate a major role for patient apathy in the effectiveness and initiation of CRF-targeting interventions. Behavioral therapies focusing on reduction in apathy should be considered as initial treatment of CRF in those with substantial apathy.

show abstract

Methylphenidate does not enhance visual working memory but benefits motivation in macaque monkeys

Cited by 11 publications

References 127 publications

Methylphenidate as a causal test of translational and basic neural coding hypotheses

Methylphenidate as a causal test of translational and basic neural coding hypotheses

Slot-like capacity and resource-like coding in a neural model of multiple-item working memory

A central role for apathy in the effectiveness of interventions for cancer‐related fatigue

Contact Info

Product

Resources

About