scholarly journals Quantifying the inverted U: A meta-analysis of prefrontal dopamine, D1-receptors, and working memory

2021 ◽  
Author(s):  
Matthew A. Weber ◽  
Mackenzie M. Conlon ◽  
Hannah R. Stutt ◽  
Linder Wendt ◽  
Patrick Ten Eyck ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Function ◽  
Memory Performance ◽  
Meta Analysis ◽  
Quantitative Relationship ◽  
D1 Receptors ◽  
Hyperactivity Disorder ◽  
Human Disorders ◽  
High Level ◽  
And Behavior

Dopamine in the prefrontal cortex can be disrupted in human disorders that affect cognitive function such as Parkinson's disease (PD), attention-deficit hyperactivity disorder (ADHD), and schizophrenia. Dopamine has a powerful effect on prefrontal circuits via the D1-type dopamine receptor (D1DR). It has been proposed that prefrontal dopamine has "inverted U-shaped" dynamics, with optimal dopamine and D1DR signaling required for optimal cognitive function. However, the quantitative relationship between prefrontal dopamine and cognitive function is not clear. Here, we conducted a meta-analysis of published manipulations of prefrontal dopamine and the effects on working memory, a high-level executive function in humans, primates, and rodents that involves maintaining and manipulating information over seconds to minutes. We reviewed 646 papers and found that 75 studies met criteria for inclusion. Our quantification of effect sizes for dopamine, D1DRs, and behavior revealed a negative quadratic slope. This is consistent with the proposed inverted U-shape of prefrontal dopamine and D1DRs and working memory performance, explaining 10% of the variance. Of note, the inverted quadratic fit was much stronger for prefrontal D1DRs alone, explaining 26% of the variance, compared to prefrontal dopamine alone, explaining 10% of the variance. Taken together, these data, derived from a variety of manipulations and systems, demonstrate that optimal prefrontal dopamine signalling is linked with higher cognitive function. Our results provide insight into the fundamental dynamics of prefrontal dopamine, which could be useful for pharmacological interventions targeting prefrontal dopaminergic circuits, and into the pathophysiology of human brain disease.

scholarly journals Investigating regions of shared genetic variation in attention deficit/hyperactivity disorder and major depressive disorder: a GWAS meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Victoria Powell ◽  
Joanna Martin ◽  
Anita Thapar ◽  
Frances Rice ◽  
Richard J. L. Anney
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Genetic Correlation ◽  
Attention Deficit ◽  
Meta Analysis ◽  
Major Depressive ◽  
Hyperactivity Disorder ◽  
High Level ◽  
Genomic Regions

AbstractAttention deficit/hyperactivity disorder (ADHD) demonstrates a high level of comorbidity with major depressive disorder (MDD). One possible contributor to this is that the two disorders show high genetic correlation. However, the specific regions of the genome that may be responsible for this overlap are unclear. To identify variants associated with both ADHD and MDD, we performed a meta-analysis of GWAS of ADHD and MDD. All genome wide significant (p < 5 × 10–8) SNPs in the meta-analysis that were also strongly associated (p < 5 × 10–4) independently with each disorder were followed up. These putatively pleiotropic SNPs were tested for additional associations across a broad range of phenotypes. Fourteen linkage disequilibrium-independent SNPs were associated with each disorder separately (p < 5 × 10–4) and in the cross-disorder meta-analysis (p < 5 × 10–8). Nine of these SNPs had not been highlighted previously in either individual GWAS. Evidence supported nine of the fourteen SNPs acting as eQTL and two as brain eQTL. Index SNPs and their genomic regions demonstrated associations with other mental health phenotypes. Through conducting meta-analysis on ADHD and MDD only, our results build upon the previously observed genetic correlation between ADHD and MDD and reveal novel genomic regions that may be implicated in this overlap.

Effect of N-methyl-D-aspartate-receptor-enhancing agents on cognition in patients with schizophrenia: A systematic review and meta-analysis of double-blind randomised controlled trials

2019 ◽  
Vol 33 (4) ◽  
pp. 436-448 ◽  
Author(s):  
Chun-Hung Chang ◽  
Hsien-Yuan Lane ◽  
Ping-Tao Tseng ◽  
Shaw-Ji Chen ◽  
Chieh-Yu Liu ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Function ◽  
Nmda Receptor ◽  
Rating Scales ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Double Blind ◽  
Cognitive Domains ◽  
Positive Effects ◽  
Statistical Heterogeneity

Background: Multiple N-methyl-d-aspartate (NMDA)-receptor-enhancing agents have demonstrated promising effects for cognition in schizophrenia. However, the results of studies have been conflicting. This updated meta-analysis explored the effect of NMDA-receptor-enhancing agents on cognitive function. Methods: We searched PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials and Cochrane Systematic Reviews for studies on the effect of NMDA-receptor-enhancing agents on cognitive function in patients with schizophrenia up to September 2018. Double-blind randomised placebo trials with cognition rating scales were included. We pooled studies by using a random-effect model for comparisons with add-on NMDA-receptor-enhancing agents. Cognitive function scores were compared between baseline and subsequent levels, and NMDA-receptor-positive modulators were assessed using the standardised mean difference (SMD) with 95% confidence intervals (CIs). We evaluated statistical heterogeneity through visual inspection of funnel plots and by using the I2 statistic. Results: We identified 25 trials with 1951 participants meeting the inclusion criteria. NMDA-receptor-enhancing agents had a small but nonsignificant effect compared with the placebo on overall cognitive function (SMD = 0.068, CI = −0.056 to 0.193, P = 0.283). We identified trials enrolling patients aged between 30 and 39 years old, which reported significant positive effects (SMD: 0.163, 95% CI: 0.016–0.310, P = 0.030). Men were associated with a smaller effect of NMDA-receptor-positive modulators on overall cognitive function. Moreover, subgroup meta-analysis of cognitive domains revealed that N-acetyl cysteine (NAC) had a significant effect on working memory ( P-value for interaction = 0.038; SMD = 0.679, CI = 0.397–0.961, P < 0.001). Conclusions: Our meta-analysis revealed no significant effect of NMDA-enhancing agents on overall cognition. However, subgroup analysis suggested that NMDAR-enhancing agents may benefit young patients with schizophrenia, and NAC may have an effect on working memory. Additional trials with larger samples are suggested to evaluate these cognitive domains and ascertain the possible mechanisms.

scholarly journals Executive Function in Children with Attention Deficit/Hyperactivity Disorder: The NIH EXAMINER Battery

2013 ◽  
Vol 20 (1) ◽  
pp. 41-51 ◽  
Author(s):  
Jane E. Schreiber ◽  
Katherine L. Possin ◽  
Jonathan M. Girard ◽  
Celiane Rey-Casserly
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Working Memory ◽  
Executive Function ◽  
Cognitive Control ◽  
Attention Deficit ◽  
Memory Performance ◽  
Parent Report ◽  
Learning Problems ◽  
Children With Adhd ◽  
Hyperactivity Disorder

AbstractTheories of attention deficit/hyperactivity disorder (ADHD) increasingly highlight the role of neuropsychological impairment in ADHD; however, a consistent and identifiable pattern of performance on tests is not well established. The National Institutes of Health (NIH) Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) battery provides measures of common variance across multiple executive function tests within specific domains and was used to characterize which executive functions are most affected in children with ADHD. Thirty-two children (24 male), ages 8–15 years (M = 12.02; SD = 2.29), diagnosed with ADHD and no comorbid disorder completed the NIH EXAMINER battery. Sixty age and gender matched healthy controls were chosen from a database of participants enrolled in the NIH EXAMINER multi-site study. Children with ADHD performed worse on the working memory score compared with the controls. No differences were found on the cognitive control or fluency scores. For children with ADHD, poorer working memory performance predicted parent report of child learning problems. Cognitive control and fluency scores did not predict learning problems. In summary, working memory emerges as a primary impairment in children with ADHD who have no comorbid disorders. Furthermore, working memory weaknesses may underlie the academic problems often seen in children with ADHD. (JINS, 2013, 19, 1–11)

scholarly journals CDH13is associated with working memory performance in attention deficit/hyperactivity disorder

2011 ◽  
Vol 10 (8) ◽  
pp. 844-851 ◽  
Author(s):  
A. Arias-Vásquez ◽  
M. E. Altink ◽  
N. N. J. Rommelse ◽  
D. I. E. Slaats-Willemse ◽  
C. J. M. Buschgens ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Working Memory ◽  
Attention Deficit ◽  
Memory Performance ◽  
Hyperactivity Disorder

scholarly journals Common default mode network dysfunction across psychopathologies: A neuroimaging meta-analysis of the n-back working memory paradigm

2020 ◽  
Author(s):  
Michael C Farruggia ◽  
Angela R Laird ◽  
Aaron T Mattfeld
Keyword(s):  
Bipolar Disorder ◽  
Working Memory ◽  
Memory Performance ◽  
Meta Analysis ◽  
Healthy Individuals ◽  
Research Domain Criteria ◽  
Default Mode ◽  
Within Subjects ◽  
The Brain ◽  
Research Domain

ABSTRACTThe National Institute of Mental Health’s (NIMH) Research Domain Criteria (RDoC) classifies disorders based on shared aspects of behavioral and neurobiological dysfunction. One common behavioral deficit observed in various psychopathologies, namely ADHD, addiction, bipolar disorder, depression, and schizophrenia, is a deficit in working memory performance. However, it is not known to what extent, if any, these disorders share common neurobiological abnormalities that contribute to decrements in performance. The goal of the present study was to examine convergence and divergence of working memory networks across psychopathologies. We used the Activation Likelihood Estimate (ALE) meta-analytic technique to collapse prior data obtained from published studies using the n-back working memory paradigm in individuals with a DSM-criteria diagnosis of the aforementioned disorders. These studies examined areas in the brain that showed increases in activity as a function of working memory-related load compared to a baseline condition, both within subjects and between healthy individuals and those with psychiatric disorder. A meta-analysis of 281 foci covering 81 experiments and 2,629 participants found significant convergence of hyperactivity in medial prefrontal cortex (mPFC) for DSM-diagnosed individuals compared to healthy controls. Foci from ADHD, addiction, bipolar disorder, schizophrenia, and major depression studies contributed to the formation of this cluster. These results provide evidence that default-mode intrusion may constitute a shared seed of dysregulation across multiple psychopathologies, ultimately resulting in poorer working memory performance.

scholarly journals Behavior-dependent directional tuning in the human visual-navigation network

2019 ◽  
Author(s):  
Matthias Nau ◽  
Tobias Navarro Schröder ◽  
Markus Frey ◽  
Christian F. Doeller
Keyword(s):  
Memory Performance ◽  
Visual Navigation ◽  
Human Cognition ◽  
Neural Population ◽  
Population Activity ◽  
Directional Tuning ◽  
Memory Processing ◽  
Depth Analysis ◽  
High Level ◽  
And Behavior

AbstractThe brain derives cognitive maps from sensory experience that guide memory formation and behavior. Despite extensive efforts, it still remains unclear how the underlying population activity relates to active behavior and memory performance. To examine these processes, we here combined 7T-fMRI with a kernel-based encoding model of virtual navigation to map world-centered directional tuning across the human cortex. First, we present an in-depth analysis of directional tuning in visual, retrosplenial, parahippocampal and medial temporal cortices. Second, we show that tuning strength, width and topology of this directional code during memory-guided navigation depend on successful encoding of the environment. Finally, we show that participants’ locomotory state influences this tuning in sensory and mnemonic regions such as the hippocampus. We demonstrate a direct link between neural population tuning and human cognition and show that high-level memory processing interacts with network-wide environmental coding in the service of behavior.

Characteristics of Healthy Older Adults that Influence Self-rated Cognitive Function

2017 ◽  
Vol 24 (1) ◽  
pp. 57-66 ◽  
Author(s):  
Bryce P. Mulligan ◽  
Colette M. Smart ◽  
Sidney J. Segalowitz ◽  
Stuart W.S. MacDonald
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Cognitive Function ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Healthy Aging ◽  
Memory Performance ◽  
Short Term ◽  
Healthy Older Adults ◽  
Subjective Cognitive Function

AbstractObjectives: We sought to clarify the nature of self-reported cognitive function among healthy older adults by considering the short-term, within-person association (coupling) of subjective cognitive function with objective cognitive performance. We expected this within-person coupling to differ between persons as a function of self-perceived global cognitive decline and depression, anxiety, or neuroticism. Methods: This was an intensive measurement (short-term longitudinal) study of 29 older adult volunteers between the ages of 65 and 80 years without an existing diagnosis of dementia or mild cognitive impairment. Baseline assessment included neuropsychological testing and self-reported depression, anxiety, and neuroticism, as well as self- and informant-reported cognitive decline (relative to 10 years previously). Intensive within-person measurement occasions included subjective ratings of cognitive function paired with performance on a computerized working memory (n-back) task; each participant attended four or five assessments separated by intervals of at least one day. Statistical analysis was comprised of multilevel linear regression. Results: Comparison of models suggested that both neuroticism and self-rated cognitive decline explained unique variance in the within-person, across-occasion coupling of subjective cognitive function with objective working memory performance. Conclusions: Self-ratings of cognition may accurately reflect day-to-day variations in objective cognitive performance among older adults, especially for individuals lower in neuroticism and higher in self-reported cognitive decline. Clinicians should consider these individual differences when determining the validity of complaints about perceived cognitive declines in the context of otherwise healthy aging. (JINS, 2018, 24, 57–66)

scholarly journals Memory performance, oral comprehension and learning process between children with attention deficit hyperactivity disorder and children with anxiety disorder

Revista CEFAC ◽  
2018 ◽  
Vol 20 (6) ◽  
pp. 692-702 ◽  
Author(s):  
Patrícia Aparecida Zuanetti ◽  
Marília Buzzo Lugli ◽  
Ângela Cristina Pontes Fernandes ◽  
Mônica da Silva Trabuco Soares ◽  
Kelly da Silva ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Working Memory ◽  
Anxiety Disorder ◽  
Episodic Memory ◽  
Attention Deficit ◽  
Memory Performance ◽  
Phonological Loop ◽  
Group Comparison ◽  
Children With Adhd ◽  
Hyperactivity Disorder

ABSTRACT Purpose: to compare aspects of memory, learning and oral comprehension between children with Attention Deficit Hyperactivity Disorder (ADHD) and children with Anxiety Disorder (AD). Methods: thirty-two children (7-10 years) were divided into: G1 - children diagnosed with ADHD, and G2 - children diagnosed with AD. The children were not under drug treatment. The tests applied assessed working memory (phonological loop and visuospatial sketch), learning, episodic memory and oral comprehension. Results: both groups showed changes in working memory for visuospatial sketch and phonological loop (worse performance in pseudowords in the ADHD group and digit-reversed order for children with AD), and in oral comprehension. Group comparison showed a statistically significant difference regarding the most complex level of the oral comprehension test and the repetition of nonwords with three syllables. Both groups showed a suitable performance in learning ability, however, the group of children with ADHD suffered from backward interference, with no memory consolidation, showing low episodic memory performance. Conclusion: children with ADHD and anxiety disorder showed various altered cognitive skills, although group comparison revealed that children with ADHD exhibited worse cognitive performance.

scholarly journals Working memory and left medial temporal cortical thickness

2016 ◽  
Vol 74 (10) ◽  
pp. 785-790
Author(s):  
Giuseppe Pastura ◽  
Tadeu Takao Almodovar Kubo ◽  
Maria Angélica Regalla ◽  
Cíntia Machado Mesquita ◽  
Gabriel Coutinho ◽  
...  
Keyword(s):  
Working Memory ◽  
Cortical Thickness ◽  
Medial Temporal Lobe ◽  
Digit Span ◽  
Memory Performance ◽  
Healthy Children ◽  
Hyperactivity Disorder ◽  
Magnetic Resonance Scan ◽  
Thickness Measurements ◽  
First Time

ABSTRACT Objective To perform a pilot study to investigate the association between working memory and cortical thickness in a sample of attention deficit/hyperactivity disorder (ADHD) children. Methods Seventeen children aged 7-10 years diagnosed with ADHD and 16 healthy children underwent a magnetic resonance scan for cortical thickness measurements. Data was correlated with working memory performance using the Backwards Digit Span subtest of the Wechsler Intelligence Scale for Children. Results Working memory impairment, evidenced by lower scores on the Backwards Digit Span, was observed in patients with ADHD compared to healthy controls. There was a direct correlation between working memory and cortical thickness of the left medial temporal lobe (Spearman’s correlation coefficient: 0.499; p < 0.005). Conclusions Our data suggests, for the first time, a correlation between working memory, evaluated by the Backwards Digit Span, and left medial temporal cortical thickness.

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