Publications by authors named "David J Marcus"

20 Publications

  • Page 1 of 1

Ventral tegmental area GABAergic inhibition of cholinergic interneurons in the ventral nucleus accumbens shell promotes reward reinforcement.

Nat Neurosci 2021 10 12;24(10):1414-1428. Epub 2021 Aug 12.

Department of Anesthesiology, Washington University in St. Louis, St. Louis, MO, USA.

The long-range GABAergic input from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) is relatively understudied, and therefore its role in reward processing has remained unknown. In the present study, we show, in both male and female mice, that long-range GABAergic projections from the VTA to the ventral NAc shell, but not to the dorsal NAc shell or NAc core, are engaged in reward and reinforcement behavior. We show that this GABAergic projection exclusively synapses on to cholinergic interneurons (CINs) in the ventral NAc shell, thereby serving a specialized function in modulating reinforced reward behavior through the inhibition of ventral NAc shell CINs. These findings highlight the diversity in the structural and functional topography of VTA GABAergic projections, and their neuromodulatory interactions across the dorsoventral gradient of the NAc shell. They also further our understanding of neuronal circuits that are directly implicated in neuropsychiatric conditions such as depression and addiction.
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http://dx.doi.org/10.1038/s41593-021-00898-2DOI Listing
October 2021

Where ketamine and dopamine collide.

Elife 2021 06 17;10. Epub 2021 Jun 17.

Department of Anesthesiology and Pain Medicine, Center for Neurobiology of Addiction, Pain, and Emotion, and Department of Pharmacology, University of Washington, Seattle, United States.

Ketamine strengthens connections between two brain regions that are involved in the production and regulation of dopamine, which may explain how the drug can alleviate depression.
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http://dx.doi.org/10.7554/eLife.70148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211445PMC
June 2021

A locus coeruleus to dentate gyrus noradrenergic circuit modulates aversive contextual processing.

Neuron 2021 07 2;109(13):2116-2130.e6. Epub 2021 Jun 2.

Department of Anesthesiology, Division of Basic Research, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Bioengineering, University of Washington, Seattle, WA 98105, USA; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195, USA; Center for the Neurobiology of Addiction, Pain and Emotion, University of Washington, Seattle, WA 98195, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA; Departments of Anesthesiology and Pharmacology, University of Washington, Seattle, WA 98195, USA. Electronic address:

Dysregulation in contextual processing is believed to affect several forms of psychopathology, such as post-traumatic stress disorder (PTSD). The dentate gyrus (DG), a subregion of the hippocampus, is thought to be an important brain region for disambiguating new experiences from prior experiences. Noradrenergic (NE) neurons in the locus coeruleus (LC) are more tonically active during stressful events and send dense projections to the DG, yet an understanding of their function in DG-dependent contextual discrimination has not been established. Here, we isolate a key function of the LC-NE-DG circuit in contextual aversive generalization using selective manipulations and in vivo single-cell calcium imaging. We report that activation of LC-NE neurons and terminal activity results in contextual generalization. We found that these effects required β-adrenergic-mediated modulation of hilar interneurons to ultimately promote aversive generalization, suggesting that disruption of noradrenergic tone may serve as an important avenue for treating stress-induced disorders.
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http://dx.doi.org/10.1016/j.neuron.2021.05.006DOI Listing
July 2021

Neuropsychological Phenotypes of Pediatric Anti-Myelin Oligodendrocyte Glycoprotein Associated Disorders: A Case Series.

Neuropediatrics 2021 06 12;52(3):212-218. Epub 2021 Feb 12.

Department of Neurology, Children's Healthcare of Atlanta, and Emory University School of Medicine, Atlanta, Georgia, United States.

Emerging research has demonstrated that anti-myelin oligodendrocyte associated disorders (MOG-AD) are associated with a less severe clinical course than demyelinating conditions associated with the presence of aquaporin-4 antibodies. While a heterogeneity of neuropsychological outcomes in pediatric demyelinating conditions have been described in the literature, no studies to date have investigated the neuropsychological sequelae of pediatric MOG-AD specifically. The objective of the present case series was to describe the clinical and neuropsychological phenotypes of seven pediatric patients (ages 3-15 years) with MOG-AD of different diagnoses (e.g., acute disseminated encephalomyelitis, optic neuritis, multiple sclerosis, and neuromyelitis spectrum disorders). Neuropsychological outcomes were evaluated by retrospective chart review. Results indicated largely intact neuropsychological profiles in five of the seven patients, with mild weaknesses in attention, executive functioning, processing speed, visual-motor/fine-motor skills, and mood concerns being observed. Two patients with a Kurtzke Extended Disability Status Scale of 0 still demonstrated findings on neuropsychological testing. Of the other two patients, one demonstrated higher levels of impairment in the context of a complex medical history and premorbid learning difficulties, while the other demonstrated declines in functioning likely associated with an earlier age of onset. Findings suggest that neuropsychological outcomes may be correspondingly less severe in this population compared with what has previously been described in the pediatric demyelinating disease literature. This differential impact may contribute to the heterogeneity of neuropsychological outcomes found in previous studies, and future research should separate participants with myelin oligodendrocyte antibodies given the difference in clinical course, treatment outcomes, and neuropsychological sequelae.
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http://dx.doi.org/10.1055/s-0041-1723955DOI Listing
June 2021

Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening.

Neuron 2020 03 13;105(6):1062-1076.e6. Epub 2020 Jan 13.

Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, USA; The Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232, USA; Departments of Pharmacology and Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Vanderbilt Center for Addiction Research, Nashville, TN 37232, USA. Electronic address:

Functional coupling between the amygdala and the dorsomedial prefrontal cortex (dmPFC) has been implicated in the generation of negative affective states; however, the mechanisms by which stress increases amygdala-dmPFC synaptic strength and generates anxiety-like behaviors are not well understood. Here, we show that the mouse basolateral amygdala (BLA)-prelimbic prefrontal cortex (plPFC) circuit is engaged by stress and activation of this pathway in anxiogenic. Furthermore, we demonstrate that acute stress exposure leads to a lasting increase in synaptic strength within a reciprocal BLA-plPFC-BLA subcircuit. Importantly, we identify 2-arachidonoylglycerol (2-AG)-mediated endocannabinoid signaling as a key mechanism limiting glutamate release at BLA-plPFC synapses and the functional collapse of multimodal 2-AG signaling as a molecular mechanism leading to persistent circuit-specific synaptic strengthening and anxiety-like behaviors after stress exposure. These data suggest that circuit-specific impairment in 2-AG signaling could facilitate functional coupling between the BLA and plPFC and the translation of environmental stress to affective pathology.
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http://dx.doi.org/10.1016/j.neuron.2019.12.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992313PMC
March 2020

An endocannabinoid-regulated basolateral amygdala-nucleus accumbens circuit modulates sociability.

J Clin Invest 2020 04;130(4):1728-1742

Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Deficits in social interaction (SI) are a core symptom of autism spectrum disorders (ASDs); however, treatments for social deficits are notably lacking. Elucidating brain circuits and neuromodulatory signaling systems that regulate sociability could facilitate a deeper understanding of ASD pathophysiology and reveal novel treatments for ASDs. Here we found that in vivo optogenetic activation of the basolateral amygdala-nucleus accumbens (BLA-NAc) glutamatergic circuit reduced SI and increased social avoidance in mice. Furthermore, we found that 2-arachidonoylglycerol (2-AG) endocannabinoid signaling reduced BLA-NAc glutamatergic activity and that pharmacological 2-AG augmentation via administration of JZL184, a monoacylglycerol lipase inhibitor, blocked SI deficits associated with in vivo BLA-NAc stimulation. Additionally, optogenetic inhibition of the BLA-NAc circuit markedly increased SI in the Shank3B-/- mouse, an ASD model with substantial SI impairment, without affecting SI in WT mice. Finally, we demonstrated that JZL184 delivered systemically or directly to the NAc also normalized SI deficits in Shank3B-/- mice, while ex vivo JZL184 application corrected aberrant NAc excitatory and inhibitory neurotransmission and reduced BLA-NAc-elicited feed-forward inhibition of NAc neurons in Shank3B-/- mice. These data reveal circuit-level and neuromodulatory mechanisms regulating social function relevant to ASDs and suggest 2-AG augmentation could reduce social deficits via modulation of excitatory and inhibitory neurotransmission in the NAc.
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http://dx.doi.org/10.1172/JCI131752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108917PMC
April 2020

c-Jun N terminal kinase signaling pathways mediate cannabinoid tolerance in an agonist-specific manner.

Neuropharmacology 2020 03 20;164:107847. Epub 2019 Nov 20.

Department of Anesthesiology and Perioperative Medicine, Penn State University College of Medicine, Hershey, PA, 17033, USA. Electronic address:

Tolerance to the antinociceptive effects of cannabinoids represents a significant limitation to their clinical use in managing chronic pain. Tolerance likely results from desensitization and down-regulation of the cannabinoid type 1 receptor (CBR), with CBR desensitization occurring via phosphorylation of CBRs by a G protein-coupled receptor kinase and subsequent association with an arrestin protein. Previous studies have shown that (1) desensitization-resistant S426A/S430A mice exhibit a modest delay in tolerance for Δ-THC and (-)-CP55,940 but a more pronounced disruption in tolerance for WIN 55,212-2 and (2) that c-Jun N-terminal kinase (JNK) signaling may selectively mediate antinociceptive tolerance to morphine compared to other opioid analgesics. In the current study, we found that pretreatment with the JNK inhibitor SP600125 (3 mg/kg) attenuates tolerance to the antinociceptive in the formalin test and to the anti-allodynic effects of Δ-THC (6 mg/kg) in cisplatin-evoked neuropathic pain using wild-type mice. We also find that SP600125 causes an especially robust reduction in tolerance to the antinociceptive effects of Δ-THC (30 mg/kg), but not WIN 55,212-2 (10 mg/kg) in the tail-flick assay using S426A/S430A mice. Interestingly, SP600125 pretreatment accelerated tolerance to the antinociceptive and anti-allodynic effects of (-)-CP55,940 (0.3 mg/kg) in mice with acute and neuropathic pain. These results demonstrate that inhibition of JNK signaling pathways delay tolerance to Δ-THC, but not to CP55,940 or WIN55,212-2, demonstrating that the mechanisms of cannabinoid tolerance are agonist-specific.
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http://dx.doi.org/10.1016/j.neuropharm.2019.107847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190707PMC
March 2020

Arrestin-3 scaffolding of the JNK3 cascade suggests a mechanism for signal amplification.

Proc Natl Acad Sci U S A 2019 01 27;116(3):810-815. Epub 2018 Dec 27.

Department of Pharmacology, Vanderbilt University, Nashville, TN 32232;

Scaffold proteins tether and orient components of a signaling cascade to facilitate signaling. Although much is known about how scaffolds colocalize signaling proteins, it is unclear whether scaffolds promote signal amplification. Here, we used arrestin-3, a scaffold of the ASK1-MKK4/7-JNK3 cascade, as a model to understand signal amplification by a scaffold protein. We found that arrestin-3 exhibited >15-fold higher affinity for inactive JNK3 than for active JNK3, and this change involved a shift in the binding site following JNK3 activation. We used systems biochemistry modeling and Bayesian inference to evaluate how the activation of upstream kinases contributed to JNK3 phosphorylation. Our combined experimental and computational approach suggested that the catalytic phosphorylation rate of JNK3 at Thr-221 by MKK7 is two orders of magnitude faster than the corresponding phosphorylation of Tyr-223 by MKK4 with or without arrestin-3. Finally, we showed that the release of activated JNK3 was critical for signal amplification. Collectively, our data suggest a "conveyor belt" mechanism for signal amplification by scaffold proteins. This mechanism informs on a long-standing mystery for how few upstream kinase molecules activate numerous downstream kinases to amplify signaling.
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http://dx.doi.org/10.1073/pnas.1819230116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338856PMC
January 2019

ProSAAS-derived peptides are regulated by cocaine and are required for sensitization to the locomotor effects of cocaine.

J Neurochem 2017 11;143(3):268-281

Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, USA.

To identify neuropeptides that are regulated by cocaine, we used a quantitative peptidomic technique to examine the relative levels of neuropeptides in several regions of mouse brain following daily intraperitoneal administration of 10 mg/kg cocaine or saline for 7 days. A total of 102 distinct peptides were identified in one or more of the following brain regions: nucleus accumbens, caudate putamen, frontal cortex, and ventral tegmental area. None of the peptides detected in the caudate putamen or frontal cortex were altered by cocaine administration. Three peptides in the nucleus accumbens and seven peptides in the ventral tegmental area were significantly decreased in cocaine-treated mice. Five of these ten peptides are derived from proSAAS, a secretory pathway protein and neuropeptide precursor. To investigate whether proSAAS peptides contribute to the physiological effects of psychostimulants, we examined acute responses to cocaine and amphetamine in the open field with wild-type (WT) and proSAAS knockout (KO) mice. Locomotion was stimulated more robustly in the WT compared to mutant mice for both psychostimulants. Behavioral sensitization to amphetamine was not maintained in proSAAS KO mice and these mutants failed to sensitize to cocaine. To determine whether the rewarding effects of cocaine were altered, mice were tested in conditioned place preference (CPP). Both WT and proSAAS KO mice showed dose-dependent CPP to cocaine that was not distinguished by genotype. Taken together, these results suggest that proSAAS-derived peptides contribute differentially to the behavioral sensitization to psychostimulants, while the rewarding effects of cocaine appear intact in mice lacking proSAAS.
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http://dx.doi.org/10.1111/jnc.14209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5693316PMC
November 2017

Mice expressing a "hyper-sensitive" form of the CB1 cannabinoid receptor (CB1) show modestly enhanced alcohol preference and consumption.

PLoS One 2017 20;12(4):e0174826. Epub 2017 Apr 20.

Department of Psychological and Brain Sciences and The Linda and Jack Gill Center for Biomolecular Science, Indiana University, Bloomington, IN, United States of America.

We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6%) but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg), morphine (10 mg/kg), and cocaine (10 mg/kg), demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0174826PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398885PMC
September 2017

Endocannabinoid signalling modulates susceptibility to traumatic stress exposure.

Nat Commun 2017 03 28;8:14782. Epub 2017 Mar 28.

Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.

Stress is a ubiquitous risk factor for the exacerbation and development of affective disorders including major depression and posttraumatic stress disorder. Understanding the neurobiological mechanisms conferring resilience to the adverse consequences of stress could have broad implications for the treatment and prevention of mood and anxiety disorders. We utilize laboratory mice and their innate inter-individual differences in stress-susceptibility to demonstrate a critical role for the endogenous cannabinoid 2-arachidonoylglycerol (2-AG) in stress-resilience. Specifically, systemic 2-AG augmentation is associated with a stress-resilient phenotype and enhances resilience in previously susceptible mice, while systemic 2-AG depletion or CB1 receptor blockade increases susceptibility in previously resilient mice. Moreover, stress-resilience is associated with increased phasic 2-AG-mediated synaptic suppression at ventral hippocampal-amygdala glutamatergic synapses and amygdala-specific 2-AG depletion impairs successful adaptation to repeated stress. These data indicate amygdala 2-AG signalling mechanisms promote resilience to adverse effects of acute traumatic stress and facilitate adaptation to repeated stress exposure.
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http://dx.doi.org/10.1038/ncomms14782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379055PMC
March 2017

Mice Expressing a "Hyper-Sensitive" Form of the Cannabinoid Receptor 1 (CB1) Are Neither Obese Nor Diabetic.

PLoS One 2016 8;11(8):e0160462. Epub 2016 Aug 8.

Gill Center for Biomolecular Science, Indiana University, Bloomington, Indiana, 47405,United States of America.

Multiple lines of evidence implicate the endocannabinoid signaling system in the modulation of metabolic disease. Genetic or pharmacological inactivation of CB1 in rodents leads to reduced body weight, resistance to diet-induced obesity, decreased intake of highly palatable food, and increased energy expenditure. Cannabinoid agonists stimulate feeding in rodents and increased levels of endocannabinoids can disrupt lipid metabolism. Therefore, the hypothesis that sustained endocannabinoid signaling can lead to obesity and diabetes was examined in this study using S426A/S430A mutant mice expressing a desensitization-resistant CB1 receptor. These mice display exaggerated and prolonged responses to acute administration of phytocannabinoids, synthetic cannabinoids, and endocannabinoids. As a consequence these mice represent a novel model for determining the effect of enhanced endocannabinoid signaling on metabolic disease. S426A/S430A mutants consumed equivalent amounts of both high fat (45%) and low fat (10%) chow control diet compared to wild-type littermate controls. S426A/S430A mutants and wild-type mice fed either high or low fat control diet displayed similar fasting blood glucose levels and normal glucose clearance following a 2 g/kg glucose challenge. Furthermore, S426A/S430A mutants and wild-type mice consumed similar amounts of chow following an overnight fast. While both THC and JZL195 significantly increased food intake two hours after injection, this increase was similar between the S426A/S430A mutant and wildtype control mice Our results indicate that S426A/S430A mutant mice expressing the desensitization-resistant form of CB1 do not exhibit differences in body weight, food intake, glucose homeostasis, or re-feeding following a fast.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160462PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976987PMC
August 2017

Tolerance to the antinociceptive effects of chronic morphine requires c-Jun N-terminal kinase.

Mol Pain 2015 Jun 12;11:34. Epub 2015 Jun 12.

Department of Anesthesiology, Penn State College of Medicine, 500 University Drive, Room C2850, Mailcode H187, 17033, Hershey, PA, USA.

Background: Morphine and fentanyl are opioid analgesics in wide clinical use that act through the μ-opioid receptor (MOR). However, one limitation of their long-term effectiveness is the development of tolerance. Receptor desensitization has been proposed as a putative mechanism driving tolerance to G protein-coupled receptor (GPCR) agonists. Recent studies have found that tolerance to morphine is mediated by the c-Jun N-terminal Kinase (JNK) signaling pathway. The goal of the present study was to test the hypotheses that: 1) JNK inhibition will be antinociceptive on its own; 2) JNK inhibition will augment morphine antinociception and; 3) JNK mediates chronic tolerance for the antinociceptive effects of morphine using acute (hotplate and tail-flick), inflammatory (10 μl of formalin 2.5%) and chemotherapy (cisplatin 5 mg/kg ip once weekly)-induced neuropathic pain assays.

Results: We found that JNK inhibition by SP600125 (3 mg/kg) produces a greater antinociceptive effect than morphine (6 mg/kg) alone in the formalin test. Moreover, co-administration of morphine (6 mg/kg) with SP600125 (3 mg/kg) produced a sub-additive antinociceptive effect in the formalin test. We also show that pre-treatment with SP600125 (3 or 10 mg/kg), attenuates tolerance to the antinociceptive effects of morphine (10 mg/kg), but not fentanyl (0.3 mg/kg), in the tail-flick and hotplate tests. Pre-treatment with SP600125 also attenuates tolerance to the hypothermic effects of both morphine and fentanyl. We also examined the role of JNK in morphine tolerance in a cisplatin-induced model of neuropathic pain. Interestingly, treatment with SP600125 (3 mg/kg) alone attenuated mechanical and cold allodynia in a chemotherapy-induced pain model using cisplatin. Strikingly, SP600125 (3 mg/kg) pre-treatment prolonged the anti-allodynic effect of morphine by several days (5 and 7 days for mechanical and cold, respectively).

Conclusions: These results demonstrate that JNK signaling plays a crucial role in mediating antinociception as well as chronic tolerance to the antinociceptive effects of morphine in acute, inflammatory, and neuropathic pain states. Thus, inhibition of JNK signaling pathway, via SP600125, represents an efficacious pharmacological approach to delay tolerance to the antinociceptive effects of chronic morphine in diverse pain models.
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http://dx.doi.org/10.1186/s12990-015-0031-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4465461PMC
June 2015

The NimStim set of facial expressions: judgments from untrained research participants.

Psychiatry Res 2009 Aug 28;168(3):242-9. Epub 2009 Jun 28.

Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, NY 10021, USA.

A set of face stimuli called the NimStim Set of Facial Expressions is described. The goal in creating this set was to provide facial expressions that untrained individuals, characteristic of research participants, would recognize. This set is large in number, multiracial, and available to the scientific community online. The results of psychometric evaluations of these stimuli are presented. The results lend empirical support for the validity and reliability of this set of facial expressions as determined by accurate identification of expressions and high intra-participant agreement across two testing sessions, respectively.
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http://dx.doi.org/10.1016/j.psychres.2008.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474329PMC
August 2009

Regulation of cognitive resources during sustained attention and working memory in 10-year-olds and adults.

Psychophysiology 2007 Jan;44(1):128-44

Institute of Child Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.

We examined differences between 10-year-olds and young adults in resource recruitment and regulation during tasks of sustained attention and spatial working memory. We administered participants spatial 0- and 1-back tasks and used pupillary dilation as a measure of resource recruitment. Repeated administration of 0-back led to smaller pupillary dilations and greater response time (RT) variability, revealing a vigilance decrement. Effects of repeated administration of 0-back and differences between 0- and 1-back in d' and RTs were similar between ages. Results further suggested that the children may not have been as effective as adults in extracting frequency information. Thus, on simple tasks of sustained attention and working memory, children recruit resources in a manner similar to adults. Finally, d' was correlated with RT variability on both tasks at both ages, highlighting the role of attentional fluctuations on both tasks.
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http://dx.doi.org/10.1111/j.1469-8986.2006.00477.xDOI Listing
January 2007

Oculomotor and manual indexes of incidental and intentional spatial sequence learning during middle childhood and adolescence.

J Exp Child Psychol 2007 Feb 7;96(2):107-30. Epub 2006 Jul 7.

Institute of Child Development, University of Minnesota, Minneapolis, MN 55455, USA.

The goal of this study was to examine incidental and intentional spatial sequence learning during middle childhood and adolescence. We tested four age groups (8-10 years, 11-13 years, 14-17 years, and young adults [18+ years]) on a serial reaction time task and used manual and oculomotor measures to examine incidental sequence learning. Participants were also administered a trial block in which they were explicitly instructed to learn a sequence. Replicating our previous study with adults, oculomotor anticipations and response times showed learning effects similar to those in the manual modality. There were few age-related differences in the sequence learning indexes during incidental learning, but intentional learning yielded differences on all indexes. Results indicate that the search for regularities and the ability to learn a sequence rapidly under incidental conditions are mature by 8 to 10 years of age. In contrast, the ability to learn a sequence intentionally, which requires cognitive resources and strategies, continues to develop through adolescence.
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http://dx.doi.org/10.1016/j.jecp.2006.05.005DOI Listing
February 2007

Oculomotor evidence of sequence learning on the serial reaction time task.

Mem Cognit 2006 Mar;34(2):420-32

University of Minnesota, Minneapolis, Minnesota, USA.

Manual and oculomotor measures of sequence learning were examined on the serial reaction time (SRT) task Participants were assigned into four groups differing on response modality (manual, oculomotor) and trial type (sequence, pseudorandom). The pattern of manual RTs replicated previous studies. Frequency of anticipatory eye movements followed similar patterns as RTs. Participants made many anticipations, even in pseudorandom blocks, and frequency of anticipations did not depend on presence of concurrent manual responses. Excluding participants with explicit awareness did not change results. Anticipations were negatively related to RTs in both incidental and intentional learning. Anticipations were positively related to sequence recall in intentional, but not incidental, learning. Results suggest that (1) anticipatory eye movements reflected sequence learning and (2) participants made overt and covert shifts of visuospatial attention to likely stimulus locations prior to stimulus onset, whether or not they made manual responses and whether or not there was a sequence.
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http://dx.doi.org/10.3758/bf03193419DOI Listing
March 2006

Attention allocation in the dual-task paradigm as measured through behavioral and psychophysiological responses.

Psychophysiology 2004 Mar;41(2):175-85

Institute of Child Development, University of Minnesota, Minneapolis, Minnesota 55455, USA.

We investigated attention allocation in a dual-task paradigm using behavioral and pupillary measures. We used an auditory digit span (DS) and a simple visual response time (RT) task. Participants were administered four conditions in which they performed neither task (no-task), a single task (DS or RT only), or both tasks (dual). Dependent variables were DS accuracy, RT, and task-evoked pupillary responses (TEPRs) to digits as estimates of mental effort. Participants maintained almost the same level of DS accuracy on dual as on DS only and sacrificed speed on the RT task. As expected, TEPRs increased linearly with memory load in both DS only and dual. Although TEPRs were initially higher in dual than in DS only, the slope of the increase was shallower in dual. Results suggest that TEPRs can elucidate mechanisms of attention allocation by distinguishing between effectiveness (level of behavioral performance) and efficiency (the costs of that performance in mental effort).
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http://dx.doi.org/10.1111/j.1469-8986.2004.00147.xDOI Listing
March 2004

Motor sequence learning and reading ability: is poor reading associated with sequencing deficits?

J Exp Child Psychol 2003 Apr;84(4):338-54

Department of Psychiatry, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.

Although it is widely assumed that children with learning disabilities have "sequencing problems," these have not been well specified. A non-verbal serial reaction time (SRT) paradigm was used to evaluate motor sequence learning in 422 children between ages 7 and 11 in relation to reading, cognitive ability level, and attention problems. The children demonstrated the response profile typically associated with motor sequence learning, but the component of the profile indicative of implicit sequence learning was not reliably associated with any of the predictors. Cognitive ability predicted overall response time; cognitive ability, reading, and attention problems each predicted overall accuracy. Explicit learning was predicted by cognitive ability, but not by reading or attention problems. Thus, we found no evidence that poor reading is preferentially associated with a domain general deficit in sequential learning.
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http://dx.doi.org/10.1016/s0022-0965(03)00030-4DOI Listing
April 2003
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