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Cited by 158Attention Deficit Hyperactivity DisorderNeural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on Behavior

Linking ADHD to the Neural Circuitry of Attention

Open access
Mueller, Adrienne, Hong, David S., Shepard, Steven, Moore, Tirin·2017·Trends in Cognitive Sciences
DOI 10.1016/j.tics.2017.03.009PMC PMC5497785
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Abstract

Attention deficit hyperactivity disorder (ADHD) is a complex condition with a heterogeneous presentation. Current diagnosis is primarily based on subjective experience and observer reports of behavioral symptoms - an approach that has significant limitations. Many studies show that individuals with ADHD exhibit poorer performance on cognitive tasks than neurotypical controls, and at least seven main functional domains appear to be implicated in ADHD. We discuss the underlying neural mechanisms of cognitive functions associated with ADHD, with emphasis on the neural basis of selective attention, demonstrating the feasibility of basic research approaches for further understanding cognitive behavioral processes as they relate to human psychopathology. The study of circuit-level mechanisms underlying executive functions in nonhuman primates holds promise for advancing our understanding, and ultimately the treatment, of ADHD.

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Crossref · 10.1016/j.tics.2017.03.009

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Claims the paper makes

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  • Findingcitation

    The authors identified seven functional domains implicated in ADHD from recent cognitive batteries.

    “We identified seven functional domains implicated in ADHD (see Figure 1] that were described in the majority of several recent cognitive batteries [5,12,16,17]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [5] Fair DA 2012 Distinct neuropsychological subgroups in typically developing youth inform heterogeneity in children with ADHD Proc Natl Acad Sci U S A 109 6769 6774 22474392 PMC3340031 source

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    • cites [16] Mostert JC 2015 Cognitive heterogeneity in adult attention deficit/hyperactivity disorder: A systematic analysis of neuropsychological measurements Eur Neuropsychopharmacol 25 2062 2074 26336867 PMC4788979 source

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  • Interpretationcitation

    The contradictory results are largely attributable to diversity in sensitivity and validity of behavioral assessments.

    “However, it is thought that these contradictory results are in large part attributable to the immense diversity in the sensitivity and validity of behavioral assessments used in these studies [91].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [91] Handbook of disruptive behavior disorders Springer 1999

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  • Premisecitation

    There is ample evidence of impairment in filtering distractors by children with ADHD compared to those without.

    “Nevertheless, there appears to be ample evidence of an impairment in the filtering of distractors by children with ADHD compared to those without (e.g. [95,97,101] ).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [95] Prior M 1985 Auditory attentional abilities in hyperactive children J Child Psychol Psychiatry 26 289 304 3980616 source

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    • cites [97] Carter CS 1995 Abnormal processing of irrelevant information in attention deficit hyperactivity disorder Psychiatry Res 56 59 70 7792343 source

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    • cites [101] Mason DJ 2003 Exploring selective attention in ADHD: Visual search through space and time J Child Psychol Psychiatry 44 1158 1176 14626457 source

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  • Premisecitation

    One or more of these structures drives selection of attended stimuli within posterior visual cortex.

    “Evidence to date suggests that one or more of these structures drives the selection of attended stimuli within posterior visual cortex (see [29] for review).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [29] Squire RF 2013 Prefrontal contributions to visual selective attention Annu Rev Neurosci 36 451 466 23841841 source

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  • Premisecitation

    Salient stimuli preferentially activate neurons in the visual system (V1, V4).

    “Although it is clear that salient stimuli preferentially activate neurons in the visual system (e.g. V1: [32]; V4: [33]), the basis of those effects remains unclear.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [32] Wang F 2015 Modulation of neuronal responses by exogenous attention in macaque primary visual cortex J Neurosci 35 13419 13429 26424888 PMC6605478 source

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    • cites [33] Burrows BE Moore T 2009 Influence and limitations of popout in the selection of salient visual stimuli by area V4 neurons J Neurosci 29 15169 15177 19955369 PMC2824599 source

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  • Classified as probably not a substantial claim. 38
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    Premisenone given

    Selective attention is one cognitive domain implicated in ADHD for which there is significant insight into underlying neural mechanisms.

    “Selective attention is one cognitive domain implicated in ADHD (see Box 2: Selective Attention Deficits in ADHD) for which there is significant insight into the underlying neural mechanisms.”
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    Premisecitation

    Cognitive flexibility may be tied to the neuromodulator acetylcholine.

    “Cognitive flexibility may also be tied to the neuromodulator acetylcholine.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Neurons in monkey area LIP exhibit activity correlated with temporal information.

    “Interestingly, a recent study by [63] showed that neurons in monkey area LIP exhibit activity that is correlated with temporal information.”
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    • cites [63] Jazayeri M Shadlen MN 2015 A neural mechanism for sensing and reproducing a time interval Curr Biol 25 2599 2609 26455307 PMC4618078 source

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    Premisecitation

    Depleting serotonin from one region of marmoset PFC did not affect attentional set shifting.

    “It has also been shown that depleting serotonin from one region of marmoset PFC did not affect attentional set shifting [61].”
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    • cites [61] Clarke HF 2005 Prefrontal serotonin depletion affects reversal learning but not attentional set shifting J Neurosci 25 532 538 15647499 PMC6725478 source

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    Premisecitation

    A large body of research has explored the effect of stimulants on ADHD symptoms.

    “A large body of research has explored the effect of stimulants, which act on catecholamine pathways, on ADHD symptoms (reviewed in e.g. [50]).”
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    • cites [50] Arnsten AF 2006 Fundamentals of attention-deficit/hyperactivity disorder: Circuits and pathways J Clin Psychiatry 67 Suppl 8 7 12 16961424

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    Premisecitation

    Numerous studies have demonstrated the importance of the prefrontal cortex for working memory.

    “Numerous studies, using a wide range of techniques, have demonstrated the importance of the prefrontal cortex for working memory (reviewed in [62]).”
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    • cites [62] Lara AH Wallis JD 2015 The role of prefrontal cortex in working memory: A mini review Front Syst Neurosci 9 26733825 PMC4683174 source

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    Premisecitation

    Exogenous and endogenous attention mechanisms are combined in LIP, SC, and FEF to generate a saliency map.

    “It has been proposed that exogenous and endogenous attention mechanisms are combined in area LIP [34], the SC [35], and the FEF (e.g. [31]) to generate a saliency map [34].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [34] Arcizet F 2011 A pure salience response in posterior parietal cortex Cereb Cortex 21 2498 2506 21422270 PMC3218666 source

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    • cites [35] Trappenberg TP 2001 A model of saccade initiation based on the competitive integration of exogenous and endogenous signals in the superior colliculus J Cogn Neurosci 13 256 271 11244550 source

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    • cites [31] Bichot NP 2015 A source for feature-based attention in the prefrontal cortex Neuron 88 832 844 26526392 PMC4655197 source

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    Premisecitation

    One study proposes that dopamine can steer cognitive flexibility through D2 dopamine receptors.

    “Alternatively, one study [60] proposes that, again, dopamine can steer cognitive flexibility, though in this case acting selectively through D2 dopamine receptors.”
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    • cites [60] Puig MV 2015 Editorial: Neuromodulation of executive circuits Front Neural Circuits 9 58 26500506 PMC4596939 source

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    Premisecitation

    Serotonergic neurons are active while rats wait for delayed rewards and blocking serotonin neuron activity results in premature responses.

    “Serotonergic neurons are active while rats wait for delayed rewards and blocking serotonin neuron activity results in premature responses [67].”
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    • cites [67] Miyazaki KW 2012 Activation of dorsal raphe serotonin neurons is necessary for waiting for delayed rewards J Neurosci 32 10451 10457 22855794 PMC6621383 source

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    Premisecitation

    Several studies in rodents have implicated serotonin in response inhibition.

    “Several studies in rodents have implicated serotonin in response inhibition (reviewed in [66]).”
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    • cites [66] Miyazaki K 2012 The role of serotonin in the regulation of patience and impulsivity Mol Neurobiol 45 213 224 22262065 PMC3311865 source

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    Interpretationcitation

    Separate endogenous and exogenous attention networks exist, but their signals are likely combined either in parietal cortex or prefrontal cortex, perhaps as a priority map.

    “Studies involving human subjects thus suggest that separate endogenous and exogenous attention networks exist, but that their signals are likely combined either in parietal cortex or the prefrontal cortex, perhaps as a priority map (reviewed in e.g. [45]).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [45] Sprague TC Serences JT 2013 Attention modulates spatial priority maps in the human occipital, parietal and frontal cortices Nat Neurosci 16 1879 1887 24212672 PMC3977704 source

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    Interpretationreasoning

    Selective attention circuits are complex, but evidence demonstrates ability to understand them using animal models and human imaging/stimulation.

    “Selective attention circuits are complex, but the evidence described above demonstrates our ability to understand them using animal models and human imaging and stimulation techniques.”
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    Premisecitation

    Changes in dopaminergic signaling have long been implicated in ADHD.

    “Regarding the latter, changes in dopaminergic signaling have long been implicated in ADHD ( [48], but see [49])”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [48] Swanson JM 2007 Etiologic subtypes of attention-deficit/hyperactivity disorder: Brain imaging, molecular genetic and environmental factors and the dopamine hypothesis Neuropsychol Rev 17 39 59 17318414 source

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    • cites [49] Gonon F 2009 The dopaminergic hypothesis of attention-deficit/hyperactivity disorder needs re-examining Trends Neurosci 32 2 8 18986716 source

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    Interpretationcitation

    Exogenous and endogenous attention are independent systems acting on the same substrate (visual cortex).

    “This and other evidence (e.g. [36]) suggests that exogenous and endogenous attention are independent systems acting on the same substrate (i.e., visual cortex).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Busse L 2008 Temporal dynamics of neuronal modulation during exogenous and endogenous shifts of visual attention in macaque area MT Proceedings Of The National Academy Of Sciences 105 16380 16385 PMC2571002 18922778 source

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    Premisecitation

    An increasing number of studies suggest ADHD could be a disorder of motivation and the reward system.

    “This review has focused on high-level cognitive phenotypes of ADHD and their underlying circuits, but there are an increasing number of studies that suggest ADHD could be a disorder of motivation and the reward system (reviewed in e.g. [68]).”
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    • cites [68] Luman M 2005 The impact of reinforcement contingencies on AD/HD: A review and theoretical appraisal Clin Psychol Rev 25 183 213 15642646 source

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    Interpretationreasoning

    This has potential to fill important gaps in current knowledge of these circuits in ADHD.

    “This has the potential to fill important gaps in current knowledge of these circuits in ADHD.”
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    Premisecitation

    One study proposes that different sub-populations with ADHD exist, with distinguishable symptoms, cognitive and physiological profiles, caused by deficits in either modulation of cortical control centers or reward circuits.

    “One study [69] proposes that different sub-populations with ADHD exist, with distinguishable symptoms, cognitive and physiological profiles, which are caused by deficits in either the modulation of cortical control centers or reward circuits.”
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    • cites [69] Sonuga-Barke EJ 2002 Psychological heterogeneity in AD/hd--a dual pathway model of behaviour and cognition Behav Brain Res 130 29 36 11864715 source

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    Premisenone given

    Many medications currently prescribed for ADHD act on dopamine release and re-uptake.

    “and many of the medications currently prescribed act on dopamine release and re-uptake.”
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    Premisecitation

    Sustained attention may be at least partially mediated by the arousal system, and gated by norepinephrine neurons in the locus coeruleus.

    “Sustained attention may be at least partially mediated by the arousal system, and gated by norepinephrine neurons in the locus coeruleus (reviewed in [18]).”
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    • cites [18] Oken BS 2006 Vigilance, alertness, or sustained attention: Physiological basis and measurement Clin Neurophysiol 117 1885 1901 16581292 PMC2865224 source

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    Premisecitation

    Cholinergic signaling in the monkey amygdala may also play a role in this switch.

    “Cholinergic signaling in the monkey amygdala may also play a role in this switch [59].”
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    • cites [59] Saez A 2015 Abstract context representations in primate amygdala and prefrontal cortex Neuron 87 869 881 26291167 PMC4574873 source

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    Interpretationcitation

    Both selective attention and working memory may be mediated by similar neuromodulatory mechanisms in spite of non-overlapping networks controlling those functions.

    “suggesting that both functions may be mediated by similar neuromodulatory mechanisms in spite of non-overlapping networks controlling those functions.”
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    Premisecitation

    Monkey homologues of the human ventral (exogenous) attention network have not yet been established.

    “Monkey homologues of the human ventral (exogenous) attention network have not yet been established [42].”
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    • cites [42] Patel GH 2015 Functional evolution of new and expanded attention networks in humans Proc Natl Acad Sci U S A 112 9454 9459 26170314 PMC4522817 source

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    Premisecitation

    Like the macaque, the marmoset's visual system closely corresponds to humans and it is capable of performing complex cognitive tasks.

    “Like the macaque, its visual system closely corresponds to humans and it is capable of performing complex cognitive tasks (e.g. [61]).”
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    • cites [61] Clarke HF 2005 Prefrontal serotonin depletion affects reversal learning but not attentional set shifting J Neurosci 25 532 538 15647499 PMC6725478 source

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    Premisecitation

    ADHD is not unique in this regard; many psychiatric disorders present with similar heterogeneity that arises from a complexity of neurological dysfunction not clearly directly related to current treatments.

    “Indeed it should be pointed out that ADHD is not unique in this regard. Many psychiatric disorders present with similar heterogeneity that arises from a complexity of neurological dysfunction not clearly directly related to current treatments (e.g. schizophrenia [74]).”
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    • cites [74] Miyamoto S 2005 Treatments for schizophrenia: A critical review of pharmacology and mechanisms of action of antipsychotic drugs Mol Psychiatry 10 79 104 15289815 source

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    Premisecitation

    Stimulants act broadly and non-specifically on dopamine and norepinephrine reuptake throughout the brain, effectively reducing symptoms for a large proportion of individuals with ADHD.

    “This problem has been somewhat elided in current practice, given that stimulants, the current cornerstone of ADHD therapy, act broadly and non-specifically on dopamine and norepinephrine reuptake throughout the brain [73], effectively reducing symptoms for a large proportion of individuals with ADHD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] Wood S 2014 Psychostimulants and cognition: A continuum of behavioral and cognitive activation Pharmacol Rev 66 193 221 24344115 PMC3880463 source

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    Premisecitation

    Several studies show that cognitive training improves ADHD symptoms, but very few use quantitative measures of cognitive performance; and their results are inconclusive.

    “Several studies show that cognitive training (regular practice of specific cognitive tasks) improves ADHD symptoms, but very few use quantitative measures of cognitive performance; and their results are inconclusive (reviewed in e.g. [83]).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [83] Rapport MD 2013 Do programs designed to train working memory, other executive functions, and attention benefit children with ADHD? A meta-analytic review of cognitive, academic, and behavioral outcomes Clin Psychol Rev 33 1237 1252 24120258 source

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    Premisenone given

    Recent research has shown that these systems are highly complex, and the ADHD phenotype cannot adequately be characterized as a dopaminergic deficit as previously thought.

    “Indeed, recent research has shown that these systems are highly complex, and the ADHD phenotype cannot adequately be characterized as a dopaminergic deficit as previously thought.”
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    Premisecitation

    While mechanistic hypotheses have been proposed for behavioral features of ADHD, empirical research validating these frameworks remains elusive.

    “While mechanistic hypotheses have been proposed for behavioral features of ADHD (e.g. [75]), empirical research validating these frameworks remains elusive.”
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    • cites [75] Killeen PR 2013 A behavioral neuroenergetics theory of ADHD Neurosci Biobehav Rev 37 625 657 23454637 source

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    Premisecitation

    Preliminary evidence in macaques shows that behavioral therapy using neurofeedback can modify cortical circuits and improve behavior.

    “Preliminary evidence in macaques shows that behavioral therapy using neurofeedback can modify cortical circuits and improve behavior [82].”
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    • cites [82] Schafer RJ Moore T 2011 Selective attention from voluntary control of neurons in prefrontal cortex Science 332 1568 1571 21617042 PMC3371378 source

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    Premisenone given

    ADHD literature to date is largely limited by the exclusively symptom-based characterization of the disorder.

    “Finally, ADHD literature to date is largely limited by the exclusively symptom-based characterization of the disorder.”
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    Interpretationreasoning

    One possibility for the lack of general ADHD symptom improvement is that individuals with ADHD have deficits in more than one domain, or that subgroups of individuals with ADHD who specifically exhibit working memory deficits should be targeted for this type of intervention.

    “therefore one possibility for the lack of general ADHD symptom improvement is that individuals with ADHD have deficits in more than one domain, or, again, that subgroups of individuals with ADHD who specifically exhibit working memory deficits should be targeted for this type of intervention.”
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    Premisenone given

    Our ability to tackle these questions in humans is limited, particularly in pediatric populations, where causal techniques such as TMS are not routinely used.

    “Unfortunately, our ability to tackle these questions in humans is limited, particularly in pediatric populations, where causal techniques such as TMS are not routinely used.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    While some studies show subsequent improvement in ADHD symptoms, others do not.

    “However, while some studies [84,85] show subsequent improvement in ADHD symptoms, others do not (e.g. [86], reviewed in e.g. [87]).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [84] Klingberg T 2002 Training of working memory in children with ADHD J Clin Exp Neuropsychol 24 781 791 12424652 source

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    • cites [85] Gropper RJ 2014 Working memory training in college students with ADHD or LD J Atten Disord 18 331 345 24420765 source

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    • cites [86] Cortese S 2015 Cognitive training for attention-deficit/hyperactivity disorder: Meta-analysis of clinical and neuropsychological outcomes from randomized controlled trials J Am Acad Child Adolesc Psychiatry 54 164 174 25721181 PMC4382075 source

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    Interpretationreasoning

    Current limitations in identifying affected cognitive domains have significant real-world consequences, including increased exposure to medications without a biological basis and increased duration of symptoms before effective therapy.

    “Our current limitations in identifying affected cognitive domains has significant real-world consequences, including increased exposure to medications without a biological basis for improving an affected domain (and associated behavioral symptoms), and increased duration of experiencing symptoms before treatment with an effective therapy.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Premisenone given

    Many challenges currently face research and clinical paradigms for quantifying and specifying symptoms and forms of ADHD.

    “Many challenges currently face research and clinical paradigms for quantifying and specifying symptoms and forms of ADHD.”
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    Interpretationreasoning

    This inadvertently results in imprecise amalgamation of underlying mechanisms.

    “However, this inadvertently results in imprecise amalgamation of underlying mechanisms.”
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  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    The study of circuit-level mechanisms underlying executive functions in nonhuman primates holds promise for advancing our understanding, and ultimately the treatment, of ADHD.

    “and the study of circuit-level mechanisms underlying executive functions in nonhuman primates holds promise for advancing our understanding, and ultimately the treatment, of ADHD.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    The marmoset breeds quickly and can more readily be genetically manipulated.

    “The marmoset also breeds quickly and can more readily be genetically manipulated [80].”
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    • cites [80] Sasaki E 2009 Generation of transgenic non-human primates with germline transmission Nature 459 523 527 19478777 source

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  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    Experimental disruption of distinct neuropsychological circuits to determine the associated behavioral deficit may provide significant insights into ADHD taxonomy.

    “Experimental disruption of distinct neuropsychological circuits to determine the associated behavioral deficit may provide significant insights into ADHD taxonomy, particularly in the ways that primary deficits converge (or diverge) on downstream behavioral deficits.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    A fuller understanding of the neural circuits and neuromodulatory systems that underlie the cognitive diversity of individuals with ADHD will be key to improving their diagnosis and treatment.

    “A fuller understanding of the neural circuits and neuromodulatory systems that underlie the cognitive diversity of individuals with ADHD will be key to improving their diagnosis and treatment.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Behavior therapy has shown some promise in addressing ADHD symptoms, but there is very little longitudinal data on this approach's effectiveness.

    “Behavior therapy, a program of behavioral correction usually guided by a clinician, has shown some promise in addressing ADHD symptoms [81], but there is very little longitudinal data on this approach’s effectiveness.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [81] Safren SA 2005 Cognitive-behavioral therapy for ADHD in medication-treated adults with continued symptoms Behav Res Ther 43 831 842 15896281 source

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    Interpretationreasoning

    Reduced reliance on the clinical diagnosis and more widespread use of well-established cognitive domains to characterize ADHD deficits in future research will allow greater capitalization on neurobiological advances and cross-species research.

    “Reduced reliance on the clinical diagnosis and more widespread use of well-established cognitive domains to characterize ADHD deficits in future research will allow greater capitalization on neurobiological advances and cross-species research.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

    Interpretationreasoning

    Future development of drugs with more specific therapeutic targets could reduce side effects and curtail unrecognized negative consequences on neurodevelopment caused by long-term non-specific increase in synaptic catecholamines.

    “However, future development of drugs with more specific therapeutic targets could reduce side effects and curtail unrecognized negative consequences on neurodevelopment caused by the long-term non-specific increase in synaptic catecholamines.”
    Quote in the paperNot a substantial claim

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    Premisenone given

    Because we have greater access to the macaque brain than we do the human, we can study the neural mechanisms at play in greater detail.

    “And finally, because we have greater access to the macaque brain than we do the human, we can study the neural mechanisms at play in greater detail.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    Current DSM-5 criteria do not differentiate between cognitive domain phenotypes.

    “Current DSM-5 criteria do not differentiate between cognitive domain phenotypes, nor is that its purpose as a diagnostic instrument.”
    Quote in the paperSubstantial claim

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    Premisecitation

    We can explore the specific effect of ADHD medication on said circuits.

    “and explore the specific effect of ADHD medication on said circuits (e.g. [76]).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [76] Rajala AZ 2012 Dissociative effects of methylphenidate in nonhuman primates: Trade-offs between cognitive and behavioral performance J Cogn Neurosci 24 1371 1381 22401288 PMC3409297 source

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  • Classified as probably not a substantial claim. May combine two claims.

    Premisereasoning

    This critical knowledge gap also exists for other commonly prescribed ADHD medications, such as alpha-2 agonists and bupropion, and can be elucidated with greater precision in non-human animal models.

    “This critical knowledge gap also exists for other commonly prescribed ADHD medications, such as alpha-2 agonists and bupropion, and can be elucidated with greater precision in non-human animal models.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Experiments probing how ADHD drugs affect animals performing these behaviors have not been exhaustive.

    “Unfortunately, experiments probing how ADHD drugs affect animals performing these behaviors have not been exhaustive (Figure 5).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisenone given

    Neurobiological mechanisms for other emerging treatment options, such as behavior therapy and cognitive training, have yet to be rigorously investigated.

    “Also, neurobiological mechanisms for other emerging treatment options, such as behavior therapy and cognitive training, have yet to be rigorously investigated.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given

    While the primary effects of first-line medications such as stimulants and atomoxetine are known, the specific mechanisms by which their up-regulation of catecholamines results in cognitive effects remain unclear.

    “While the primary effects of first-line medications such as stimulants and atomoxetine are known, the specific mechanisms by which their up-regulation of catecholamines results in cognitive effects remain unclear.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based).

    Interpretationreasoning

    With adequate tools, separation of ADHD cases into more meaningful groups may facilitate development of more selective treatments.

    “With adequate tools, we anticipate separation of ADHD cases into more meaningful groups, which may facilitate development of more selective treatments.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    Use of more nuanced cognitive tests will help characterize ADHD deficits.

    “Use of more nuanced cognitive tests will help characterize ADHD deficits”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    They appear to react to the drugs in similar ways to humans and in general there is very good correspondence in the behavioral response to drug manipulations across different species.

    “They appear to react to the drugs in similar ways to humans and in general there is very good correspondence in the behavioral response to drug manipulations across different species.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisenone given

    There are still many gaps in the literature that will be crucial to fill.

    “But there are still many gaps in the literature that will be crucial to fill.”
    Quote in the paperNot a substantial claim
54 of 54

  • The paper relies on this without support.

    ADHD is a complex condition with a heterogeneous presentation.

    “ADHD is a complex condition with a heterogeneous presentation.”

  • The paper relies on this without support.

    An etiological basis for ADHD remains elusive.

    “An etiological basis for ADHD remains elusive, as have been efforts to subtype ADHD using biological indicators, rather than solely relying on clinical assessments.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Mueller, A., Hong, D. S., Shepard, S., & Moore, T.
Affiliations
  • Stanford Medicine (US)
  • Stanford University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Mueller, Adrienne
ORCID
Venue
Trends in Cognitive Sciences
Publisher
Elsevier BV
Published
2017-06
Volume
21
Issue
6
Pages
474-488
ISSN
1364-6613 (ISSN-L)
DOI
10.1016/j.tics.2017.03.009
PMC
PMC5497785
OpenAlex
W2610969135
Cited by
158
References
165
Citations by year
2026: 7 · 2025: 21 · 2024: 18 · 2023: 15 · 2022: 25 · 2021: 18 · 2020: 12 · 2019: 27 · 2018: 11 · 2017: 4
FWCI
2.24
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Trends in Cognitive Sciences (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of Mental Health (T32MH019908)
  • National Eye Institute (R01EY014924)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
attention deficit hyperactivity disorder, selective attention, neural circuits, executive function, cognitive domain, non-human primates, ADHD diagnosis, behavioral symptoms
MeSH terms
Animals, Attention, Attention Deficit Disorder with Hyperactivity, Cognition, Humans, Models, Neurological, Executive Function

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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