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Cited by 237Attention Deficit Hyperactivity DisorderDevelopmental and Educational NeuropsychologyAutism Spectrum Disorder Research

The influences of environmental enrichment, cognitive enhancement, and physical exercise on brain development: Can we alter the developmental trajectory of ADHD?

Open access
Halperin, Jeffrey M., Healey, Dione M.·2011·Neuroscience & Biobehavioral Reviews
DOI 10.1016/j.neubiorev.2010.07.006PMC PMC3008505
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Abstract

Attention-deficit/Hyperactivity Disorder (ADHD) is characterized by a pervasive pattern of developmentally inappropriate inattentive, impulsive and hyperactive behaviors that typically begin during the preschool years and often persist into adulthood. The most effective and widely used treatments for ADHD are medication and behavior modification. These empirically-supported interventions are generally successful in reducing ADHD symptoms, but treatment effects are rarely maintained beyond the active intervention. Because ADHD is now generally thought of as a chronic disorder that is often present well into adolescence and early adulthood, the need for continued treatment throughout the lifetime is both costly and problematic for a number of logistical reasons. Therefore, it would be highly beneficial if treatments would have lasting effects that remain after the intervention is terminated. This review examines the burgeoning literature on the underlying neural determinants of ADHD along research demonstrating powerful influences of environmental factors on brain development and functioning. Based upon these largely distinct scientific literatures, we propose an approach that employs directed play and physical exercise to promote brain growth which, in turn, could lead to the development of potentially more enduring treatments for the disorder.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that medication and behavioral treatments for ADHD reduce symptoms but rarely produce lasting gains, and it proposes that environmental enrichment, cognitive challenge, and physical exercise—especially through directed play—may promote brain development and compensatory neural growth. The authors frame this as a conceptual approach that could potentially alter the developmental trajectory of ADHD rather than cure its core pathology.

Key findings

  • Stimulant medication and behavioral interventions are well-supported and improve ADHD symptoms and functioning, but benefits generally do not persist after active treatment. The review cites that 32–64% of children continued to show clinically significant ADHD despite intensive medication and behavioral treatment, and that more than half of children prescribed stimulants stop within a school year, with most adhering for fewer than two months and fewer than 10% continuing long-term medication.
  • Neuroimaging and neuropsychological evidence indicates ADHD involves differences across frontostriatal circuits and many other cortical/subcortical regions, including cerebellum and corpus callosum. One cited longitudinal line reports cortical maturation delays of 2–3 years depending on region, and a meta-analysis of 83 studies (N = 6,703) found executive-function effect sizes generally in the .46–.69 range, though such weaknesses were described as neither necessary nor sufficient to explain all ADHD.
  • The authors highlight a developmental compensation hypothesis: primary subcortical deficits may remain relatively static, while later prefrontal/executive development could reduce symptom severity. Consistent findings include links between cortical development trajectories and outcome, and the DRD4 7-repeat allele being associated with normalized cortical thinning, better outcome, higher IQ, and better global functioning.
  • Animal and limited human literature suggests environmental enrichment and exercise increase neurogenesis, dendritic branching, synaptic density, neurotrophins such as BDNF, long-term potentiation, and memory performance. In children with ADHD, only two exercise studies are cited, and neither assessed clinical response or brain changes; cognitive training studies improve working memory, attention, and some behavior, but are narrow, computer-based, and sometimes poorly retained (e.g., 18/27 completed one working-memory trial).

Methods

  • Narrative review synthesizing separate literatures on evidence-based ADHD treatments, neural substrates of ADHD, neurodevelopment, environmental enrichment, physical exercise, and cognitive training.
  • No new empirical data are collected; the paper draws on animal studies, human neuroimaging, neuropsychological meta-analyses, clinical trials, and developmental genetics.
  • The authors propose a conceptual intervention model using directed play and physical exercise, delivered in family, school, or group settings, to promote broad neural and cognitive growth.

Limitations

  • The paper states that human evidence for environmental enrichment is limited, child research is sparse, and only two exercise studies in ADHD exist, neither of which examined clinical response or brain-related changes. It also notes that data on play as a therapeutic approach are sparse and that many questions remain about clinical utility.
  • The authors acknowledge that short-term effects of the proposed play/exercise approach are unlikely to match medication effect sizes, that extended follow-up would be needed, and that they do not claim it targets the core neural pathology of ADHD.
  • Evident from the text: as a review, it offers no direct test of the proposed intervention; the approach is speculative, compliance and generalizability are uncertain, and ADHD heterogeneity may limit interventions focused on single cognitive domains.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.neubiorev.2010.07.006

Cites

262 of 262 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

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  • Premisecitation

    Gains from these interventions are rarely maintained after treatment termination.

    “However, such gains are rarely maintained after the termination of treatment (Chronis, Pelham, Jr., Gnagy, Roberts, & Aronoff, 2003; Chronis et al., 2004; Jensen et al., 2007)”
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    Several effective psychopharmacologic and behavioral interventions for ADHD are available.

    “Several effective empirically-validated psychopharmacologic and behavioral interventions for ADHD are currently available.”
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    A significant number of children with ADHD are not normalized by stimulant medication and/or behavioral interventions.

    “the behavior of a significant number of children with ADHD is not normalized by the use of these interventions (Hoza et al., 2005; Swanson et al., 2001).”
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    Swanson et al. found that 32-64% of children continued to exhibit clinically significant levels of ADHD despite intensive stimulant medication and behavioral treatment regimens.

    “Swanson and colleagues (Swanson et al., 2001) found that 32–64% of children continued to exhibit clinically significant levels of ADHD despite intensive stimulant medication and behavioral treatment regimens.”
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    In the MTA study, the pure behavioral treatment group improved to a similar degree as the community treated control group.

    “the large Multimodal Treatment Study of ADHD (MTA Study) found that their pure behavioral treatment group improved to a similar degree as their community treated control group, the majority of whom received medication treatment from their provider outside of the study (MTA Cooperative Group, 1999).”
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    Premisenone given

    These interventions ameliorate core ADHD symptoms and improve academic performance.

    “These interventions have been shown to ameliorate the core symptoms of ADHD and to improve academic performance across a wide array of school-related measures.”
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    Premisecitation

    ADHD is a chronic neurodevelopmental disorder that typically emerges in preschool, persists into adolescence and adulthood for many, and causes significant functional disability.

    “ADHD typically emerges during the preschool years, persists through adolescence and into adulthood for many afflicted individuals, and causes significant functional disability throughout the lifespan (American Psychiatric Association Task Force on DSM-IV, 2000).”
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    Premisecitation

    Stimulant medication improves core symptoms, compliance, aggression, and academic productivity.

    “Stimulant medication has been shown to improve functioning in children with ADHD, with studies demonstrating improvements in core symptoms of ADHD, compliance, aggression, and academic productivity (Conners, 2002; Greenhill et al., 1999; Spencer et al., 1996).”
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    Interpretationreasoning

    Bringing together these literatures may provide insights for developing more enduring treatments for ADHD.

    “The bringing together of these scientific literatures may provide valuable insights for the development of more enduring treatments for ADHD.”
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    Interpretationreasoning

    Given these findings, an alternative approach to ameliorating the difficulties of children with ADHD is indicated.

    “Given these findings, an alternative approach to ameliorating the difficulties of children with ADHD is indicted.”
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    Interpretationreasoning

    Although acute benefits are well-documented, lack of normalization, lack of generalization, difficulties in long-term adherence, and lack of clear improvement in long-term functioning are discouraging.

    “Thus, although acute benefits of stimulant medication and behavioral interventions are well-documented in the literature, the lack of normalization of functioning for many children following treatment, lack of generalization of treatment effects, difficulties in long-term adherence, and lack of clear improvement in long-term functioning following the use of these interventions are discouraging.”
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    Premisecitation

    Behavioral interventions are more palatable but more difficult to implement, costly, and may be less effective than stimulant medications.

    “Behavioral interventions, in contrast, are more palatable but much more difficult to implement, generally quite costly, and may be less effective than stimulant medications (MTA Cooperative Group, 1999).”
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    Interpretationcitation

    Children with ADHD may do significantly better with treatment relative to baseline, but still appear deviant relative to peers in key areas of functioning.

    “although children with ADHD may do significantly better with stimulant medication and/or behavioral interventions relative to baseline, they still appear deviant relative to their peers in key areas of functioning.”
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    Interpretationreasoning

    This suggests that behavioral and stimulant treatments temporarily suppress behavioral difficulties, which resurface when treatment is inactive.

    “This suggests that implementation of behavioral interventions and stimulant medication temporarily suppresses behavioral difficulties and that these difficulties resurface when treatment is no longer active.”
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    Premisenone given

    A distinct scientific literature, largely animal research, indicates that neurodevelopmental processes facilitate efficient neurotransmission and are highly responsive to environmental influences.

    “Additionally, a distinct scientific literature, largely consisting of research with animals, indicates that an array of neurodevelopmental processes facilitate efficient neurotransmission and are highly responsive to environmental influences.”
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    Premisecitation

    Because of the relatively modest effect sizes, it was concluded that EF weaknesses are neither necessary nor sufficient to cause all cases of ADHD.

    “because of the relatively modest effect sizes, it was concluded that EF weaknesses are “neither necessary nor sufficient to cause all cases of ADHD.””
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    Interpretationreasoning

    The extensive literature indicating neurobiological deficits in ADHD and neural rehabilitation suggests that research examining pharmacologic and environmental manipulations on neural growth and lasting cognitive function could provide a fruitful avenue for novel treatments.

    “The extensive literature indicating neurobiological deficits in ADHD, and the strong body of evidence regarding neural rehabilitation, suggests that research examining the impact of pharmacologic as well as environmental manipulations on neural growth, and lasting cognitive function, could provide a potentially fruitful avenue for novel treatment approaches for this highly impairing and oftentimes”
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    Premisecitation

    Shaw et al. found links between cortical thickness and clinical outcome: worse outcome had fixed thinning of the left medial PFC, and better outcomes had right parietal normalization.

    “Additional research from this group (Shaw et al., 2006) found links between cortical thickness and clinical outcome such that ADHD children with worse outcome had “fixed” thinning of the left medial PFC and those with better outcomes had right parietal normalization, which was suggested to represent compensatory cortical change.”
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    Better clinical outcome was linked to the presence of the DRD4-7-repeat allele, which was associated with thinner right orbitofrontal/inferior prefrontal and posterior parietal cortices.

    “better clinical outcome was linked to the presence of the DRD4-7-repeat allele (Shaw et al., 2007b), which was associated with thinner right orbitofrontal/inferior prefrontal and posterior parietal cortices.”
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    A recent review suggests that remission in ADHD with age may be linked to normalization of initial delays or deficits in brain networks, whereas persistence into adolescence may be associated with a lack of normalization and perhaps a more deviant trajectory of brain growth.

    “A recent review focusing on trajectories of brain development (Shaw, Gogtay, & Rapoport, 2010) suggests that remission in ADHD with age may be linked to a normalization of initial delays or deficits in brain networks, whereas ADHD persistence into adolescence may be associated with a lack of normalization and perhaps a more deviant trajectory of brain growth.”
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    Studies have found reduced caudate nucleus size, reduced globus pallidus volume, and reduced callosal area in ADHD.

    “studies have found reduced caudate nucleus size (Filipek et al., 1997; Hynd et al., 1993), reduced volume in the globus pallidus (Castellanos et al., 1996); and reduced callosal area in ADHD (Baumgardner et al., 1996; Giedd et al., 1994; Hynd et al., 1991; Hill et al., 2003; Hynd et al., 1991; Lyoo et al., 1996; Semrud-Clikeman et al., 1994).”
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    Premisecitation

    Studies most consistently find deficits in inhibitory control, regulation of attention, working memory, planning, and shifting sets in ADHD.

    “Studies most consistently find deficits in inhibitory control (Barkley, 1997; Casey et al., 1997; Durston et al., 2003), regulation of attention (Pennington, Groisser, & Welsh, 1993; Swanson et al., 1991; Halperin et al., 1993; Johnson et al., 2008), working memory (Castellanos et al., 2002b; Martinussen, Hayden, Hogg-Johnson, & Tannock, 2005), planning (Pennington et al., 1993; Barkley, 1997),”
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    Interpretationcitation

    These findings were interpreted as suggesting developmental delays rather than permanent anomalies in ADHD.

    “These findings were interpreted as suggesting developmental delays rather than permanent anomalies in ADHD.”
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    Premisecitation

    Two studies reported decreased functional connectivity during active task performance in children with ADHD, which may be normalized in part by stimulant medication.

    “Two studies (Rubia et al., 2010; Vloet et al., 2010) have reported decreased functional connectivity during active task performance in children with ADHD, which may in part be normalized by treatment with stimulant medication (Rubia et al., 2009).”
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    A key review found support for frontostriatal abnormalities in ADHD, but also highlighted widespread neural abnormalities affecting other cortical regions and the cerebellum.

    “A key review of the structural MRI literature (Seidman et al., 2005) found support for the notion that ADHD is associated with frontostriatal abnormalities. However, an increasing number of studies, demonstrating widespread neural abnormalities affecting other cortical regions and the cerebellum, were highlighted.”
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    Premisecitation

    The Default Mode Network (DFN) is most active during rest and deactivates during active task engagement.

    “The Default Mode Network (DFN), comprised of the precuneus, posterior cingulate cortex, the medial prefrontal cortex and portions of the parietal cortex (Schilbach, Eickhoff, Rotarska-Jagiela, Fink, & Vogeley, 2008), has been shown to be most active during rest, and to deactivate during active task engagement (Raichle et al., 2001).”
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    Some data suggest reduced functional activity and connectivity within the DFN during rest in ADHD, but others report an overactive DFN during quiescence.

    “When comparing ADHD participants to controls, some data suggest, reduced functional activity and connectivity within the DFN during rest (Castellanos et al., 2008; Uddin et al., 2008b), but others report an overactive DFN during quiescence (Tian et al., 2006; Tian et al., 2008).”
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    Premisecitation

    Psychostimulant treatment improves DFN suppression during active task engagement and decreases reaction time variability in youth with ADHD.

    “psychostimulant treatment has been found to improve DFN suppression during active task engagement in youth with ADHD (Peterson et al., 2009), as well as to decrease reaction time variability (Spencer et al., 2009).”
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    Interpretationcitation

    These findings suggest greater segregation between networks as well as improved integration within networks with increased age.

    “These findings suggest greater segregation between networks as well as improved integration within networks with increased age.”
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    Interpretationcitation

    This hypothesized developmentally-related compensation may also be related to changes in functional connectivity in the brain that occur over development.

    “This hypothesized developmentally-related compensation for earlier deficits may also be related to changes in functional connectivity in the brain that occurs over development.”
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    Premisecitation

    This hypothesis is consistent with data suggesting that trajectories of cortical development throughout middle childhood might be closely linked to ADHD outcomes, and that lower reaction time variability is associated with increased activation of the prefrontal circuit in children with ADHD.

    “This hypothesis is consistent with data suggesting that trajectories of cortical development throughout middle childhood might be closely linked to ADHD outcomes (Shaw et al., 2006; Shaw et al., 2007b), and that lower reaction time variability is associated with increased activation of the prefrontal circuit (prefrontal cortex and caudate) in children with ADHD (Suskauer et al., 2008).”
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    Premisecitation

    They posited that the reduction of symptoms often seen over development is at least partially accounted for by the degree to which prefrontally-mediated EFs and other higher cortical functions can compensate for primary and enduring subcortical deficits.

    “they posited that the reduction of symptoms oftentimes seen over development are at least partially accounted for by the degree to which prefrontally-mediated EFs and other higher cortical functions, which emerge throughout childhood and adolescence, can compensate for these more primary and enduring subcortical deficits.”
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    Dosenbach et al. described two distinct top-down functional control networks in adults: a frontoparietal network involved in adaptive online task control and a cinguloopercular network involved in more stable set control.

    “Dosenbach et al. (Dosenbach et al., 2007) described two distinct “top-down” functional control networks in adults; a frontoparietal network involved in adaptive online task control and a cinguloopercular network involved in more stable set control.”
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    Premisecitation

    More recently, it has been proposed that there may be multiple causal pathways that contribute to the emergence of ADHD in early childhood.

    “More recently, it has been proposed that there may be multiple causal pathways that contribute to the emergence of ADHD in early childhood (Nigg, Willcutt, Doyle, & Sonuga-Barke, 2005; Sonuga-Barke, 2002).”
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    Premisecitation

    As posited by Posner, the alerting network is driven largely by noradrenergic input from the locus coeruleus to the frontal and parietal lobes, whereas conflict resolution is more closely linked to a dopaminergic system involving the basal ganglia, anterior cingulate, and dorsolateral prefrontal cortex.

    “As posited by Posner and colleagues, the alerting network is driven largely by noradrenergic input from the locus coeruleus to the frontal and parietal lobes, whereas conflict resolution is more closely linked to a dopaminergic system involving the basal ganglia, anterior cingulate and the dorsolateral prefrontal cortex (Posner et al., 1990; Posner, Sheese, Odludas, & Tang, 2006).”
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    Interpretationcitation

    Studies examining cortical thickness provide compelling evidence that careful examination of developmental trajectories may be key to uncovering the neural substrates of ADHD, and that clinical outcomes might be linked to cortical development and compensatory mechanisms that develop throughout childhood.

    “Further, studies examining cortical thickness provide compelling evidence that careful examination of developmental trajectories may be key to uncovering the neural substrates of ADHD, and that clinical outcomes might be linked to cortical development and compensatory mechanisms that develop throughout childhood.”
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    Interpretationcitation

    This latter finding was interpreted as prefrontal compensation for a more primary motor deficiency.

    “This latter finding was interpreted as prefrontal compensation for a more primary motor deficiency.”
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    Premisecitation

    They hypothesized that ADHD is caused by non-cortical neural dysfunction that is present early in ontogeny and remains relatively static throughout life.

    “they hypothesized that ADHD is caused by non-cortical neural dysfunction that is present early in ontogeny and remains relatively static throughout life.”
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    Interpretationreasoning

    It is possible that these developmental processes that support the maturation of the dual-network control system play a critical role in the hypothesized compensation for earlier deficits in youth with ADHD.

    “It is possible that these developmental processes that support the maturation of this dual-network control system play a critical role in the hypothesized compensation for earlier deficits in youth with ADHD.”
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    Interpretationnone given

    Little consideration has been afforded to pathways out of ADHD or the mechanisms by which the severity of the disorder diminishes over time, which could serve as the conceptual basis for the development of novel, perhaps enduring, interventions.

    “However, little consideration has been afforded to pathways out of ADHD or the mechanisms by which the severity of the disorder diminishes over time, which could serve as the conceptual basis for the development of novel, perhaps enduring, interventions.”
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    Interpretationreasoning

    In this regard, the disorder is never really cured or out-grown.

    “In this regard, the disorder is never really “cured” or “out-grown.””
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    Premisecitation

    Epstein et al. reported variability in d', lnβ, and RT to be strongly associated across multiple ADHD symptom domains.

    “Epstein and colleagues (Epstein et al., 2003) reported variability in d’, lnβ, and RT to be strongly associated across multiple ADHD symptom domains.”
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    Premisecitation

    Rommelse et al. reported that after controlling for lower order cognitive processes, there was little evidence for primary EF deficits in children with ADHD.

    “A recent study (Rommelse et al., 2007) reported that after controlling for “lower order” cognitive processes, there was little evidence for primary EF deficits in children with ADHD.”
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    Premisecitation

    Kuntsi et al. reported that RT variability discriminated ADHD children from controls better than measures of inhibition and working memory.

    “Kuntsi and colleagues (Kuntsi et al., 2001) reported that RT variability discriminated ADHD children from controls better than measures of inhibition and working memory”
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    Premisecitation

    Halperin and colleagues have posited distinct neurocognitive mechanisms for the etiology of and relative recovery from ADHD.

    “Halperin and colleagues (Halperin et al., 2006; Halperin, Marks, & Schulz, 2008) have posited distinct neurocognitive mechanisms for the etiology of and relative recovery from ADHD.”
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    Premisecitation

    In a multisite clinical trial, Cogmed produced beneficial effects in school-aged children with ADHD on visual and verbal working memory, nonverbal complex reasoning, and response inhibition compared to low-level working memory computer task; gains maintained at 3-month follow-up on several outcomes; effects on parent but not teacher ratings of ADHD behavior and oppositionality.

    “In a multisite clinical trial (Klingberg et al., 2005), beneficial effects of Cogmed were reported in school-aged children with ADHD. Significant intervention effects were found on measures of visual (Span board) and verbal (Digit Span from the WISC-III) working memory, nonverbal complex reasoning (Raven’s Progressive Matrices), and response inhibition (Stroop task), compared to the low-level”
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    Premisecitation

    Treadmill exercise in rats increases cell proliferation via IGF-1 and cell proliferation and survival in the dentate gyrus.

    “Specifically, treadmill exercises in rats increase cell proliferation via insulin-like growth factor-1 (Trejo et al., 2001) and cell proliferation and survival in the dentate gyrus (van Praag, Kempermann, & Gage, 1999b).”
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    In spontaneously hypertensive rats (animal model for ADHD), chronic exercise blunted developmental rise of blood pressure and increased glutamic acid decarboxylase mRNA in caudal hypothalamus.

    “Perhaps more relevant to the current thesis, chronic exercise blunted the developmental rise of blood pressure while increasing glutamic acid decarboxylase mRNA in the caudal hypothalamus in spontaneously hypertensive rats, which are commonly used as an animal model for ADHD (Little, Kramer, Beatty, & Waldrop, 2001).”
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    Epidemiologic data link increased participation in intellectual and social activities in daily life with slower cognitive decline in the elderly.

    “Epidemiologic data provide a compelling link between increased participation in intellectual and social activities in daily life and a slower cognitive decline in the elderly (Scarmeas & Stern, 2004).”
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    • cites Scarmeas & Stern, 2004

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  • May combine two claims.

    Premisecitation

    Cognitive interventions for children with ADHD improve working memory, inhibition, attention, and nonverbal reasoning, and may reduce behavioral symptoms as reported by parents/teachers.

    “Collectively these studies have shown that cognitive interventions for children with ADHD improve working memory, inhibition, attention, and nonverbal reasoning ability, and may reduce behavioral symptoms of ADHD as reported by parents and/or teachers (Kerns et al., 1999; Klingberg et al., 2005; Shalev et al., 2007).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Kerns et al., 1999 source

      Not checked in the free run.

    • cites Klingberg et al., 2005 source

      Not checked in the free run.

    • cites Shalev et al., 2007

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In children with ADHD, BDNF levels are increased compared to controls, and BDNF levels correlate with neuropsychological performance (errors on continuous performance test).

    “One study that examined BDNF levels in children with ADHD reported that as compared to controls, those with ADHD had increased levels of BDNF, and that BDNF levels correlated with neuropsychological performance as indicated by number of errors on a continuous performance test (Shim et al., 2008).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Shim et al., 2008

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Brain development is highly responsive to increased levels of physical activity/exercise as well as environmental enrichment.

    “However, there is no longer doubt that brain development is highly responsive to increased levels of physical activity/exercise as well as environmental enrichment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Physical exercise increases synaptic proteins, glutamate receptors, BDNF availability, and IGF-1, which can enhance neural plasticity.

    “Physical exercise increases levels of synaptic proteins (Vaynman, Ying, Yin, & Gomez-Pinilla, 2006), glutamate receptors (Farmer et al., 2004) and the availability of brain-derived neurotrophic factor (BDNF) (Berchtold, Chinn, Chou, Kesslak, & Cotman, 2005) and insulin-like growth factor-1 (Trejo, Carro, & Torres-Aleman, 2001), all of which can enhance neural plasticity.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Vaynman, Ying, Yin, & Gomez-Pinilla, 2006

      Not checked in the free run.

    • cites Farmer et al., 2004

      Not checked in the free run.

    • cites Berchtold, Chinn, Chou, Kesslak, & Cotman, 2005 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ADHD is a heterogeneous disorder; most children have impairments in multiple cognitive domains and only a portion have deficits in any single domain.

    “The focus on a specific cognitive domain is problematic because ADHD is a heterogeneous disorder, with most children experiencing impairments in multiple cognitive domains and only a portion have deficits in any single domain (Nigg et al., 2005).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Nigg et al., 2005 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In adults, cognitive training increases cortical brain activity and alters dopamine D1 receptor binding in prefrontal and parietal cortices.

    “Furthermore, in adults, cognitive training increases cortical brain activity (Olesen, Westerberg, & Klingberg, 2004) and alters dopamine D1 receptor binding in both the prefrontal and parietal cortices (McNab et al., 2009).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Olesen, Westerberg, & Klingberg, 2004 source

      Not checked in the free run.

    • cites McNab et al., 2009 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both exercise and environmental enhancement contribute to positive neurodevelopmental outcomes, though not necessarily identically.

    “Data suggest that both exercise and environmental enhancement contribute to positive neurodevelopmental outcomes, although not necessarily in an identical manner.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Cognitive exercises show promise for slowing cognitive and functional decline associated with dementia.

    “Furthermore, cognitive exercises show promise as effective interventions for slowing the trajectory of cognitive and functional decline that is associated with dementia (Gates & Valenzuela, 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Gates & Valenzuela, 2010

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Attention training in preschool children yielded changes in executive functioning and parallel alterations in ERPs reflecting patterns typical of older individuals.

    “With regard to cognitive enhancement, Rueda et al. (Rueda, Rothbart, McCandliss, Saccomanno, & Posner, 2005) showed that attention training in preschool children yielded changes in executive functioning and parallel alterations in event related responses (ERPs) reflecting patterns typical of older individuals.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rueda, Rothbart, McCandliss, Saccomanno, & Posner, 2005

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Physical exercise enhances spatial learning and passive avoidance memory in rats.

    “These neural changes in response to physical exercise are accompanied by behavioral changes such that physical exercise enhances spatial learning (Fordyce & Farrar, 1991; Fordyce & Wehner, 1993) and passive avoidance memory (Samorajski et al., 1985).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Fordyce & Farrar, 1991

      Not checked in the free run.

    • cites Fordyce & Wehner, 1993

      Not checked in the free run.

    • cites Samorajski et al., 1985

      Not checked in the free run.

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

    Premisecitation

    Chronic play therapy reduced right frontal lesion-induced hyperactivity in juvenile rats; enhanced access to rough-and-tumble play improved behavioral inhibition in normal animals.

    “Finally, “chronic play therapy” reduced right frontal lesion-induced hyperactivity in juvenile rats, and enhanced access to rough-and-tumble play in normal animals improved performance on indices of behavioral inhibition (Panksepp, Burgdorf, Turner, & Gordon, 2003).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Panksepp, Burgdorf, Turner, & Gordon, 2003

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Problem solving and coordination manipulations increase synapse formation in the cerebellar cortex; repetitive physical exercise increases cerebellar blood vessel density.

    “Manipulations involving problem solving and coordination increase synapse formation in the cerebellar cortex (Kleim, Vij, Ballard, & Greenough, 1997; Kleim et al., 1998), whereas repetitive physical exercise increases cerebellar blood vessel density (Black, Isaacs, Anderson, Alcantara, & Greenough, 1990).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Kleim, Vij, Ballard, & Greenough, 1997

      Not checked in the free run.

    • cites Kleim et al., 1998

      Not checked in the free run.

    • cites Black, Isaacs, Anderson, Alcantara, & Greenough, 1990 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In human adults, physical exercise increases BDNF levels, enhances cognitive performance, and promotes brain health.

    “Physical exercise has also been reported to increase BDNF levels (Ferris, Williams, & Shen, 2007; Gold et al., 2003; Rasmussen et al., 2009; Seifert et al., 2010; Strohle et al., 2010; Tang, Chu, Hui, Helmeste, & Law, 2008; Zoladz et al., 2008), enhance cognitive performance (Baker et al., 2010; Ferris et al., 2007; Laurin, Verreault, Lindsay, MacPherson, & Rockwood, 2001), and to promote brain”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Ferris, Williams, & Shen, 2007 source

      Not checked in the free run.

    • cites Gold et al., 2003

      Not checked in the free run.

    • cites Rasmussen et al., 2009 source

      Not checked in the free run.

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

    Premisecitation

    Cognitive and social stimulation, as well as physical exercise, may delay onset of dementia and other neurodegenerative diseases.

    “These data suggest that cognitive and social stimulation, as well as physical exercise, may delay the onset of dementia and other neurodegenerative diseases (Scarmeas & Stern, 2004; Ravaglia et al., 2008; Kramer & Erickson, 2007; Arkin, 2007; Rolland et al., 2007).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Scarmeas & Stern, 2004

      Not checked in the free run.

    • cites Ravaglia et al., 2008

      Not checked in the free run.

    • cites Kramer & Erickson, 2007 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a randomized trial with low-income urban preschool children, Tools-based classrooms significantly improved performance on experimental measures of inhibitory control, working memory, and cognitive flexibility compared to existing literacy program; behavioral changes not assessed.

    “Results of this randomized trial demonstrated that preschool children in Tools-based classrooms significantly improved performance on experimental measures of inhibitory control, working memory, and cognitive flexibility. Behavioral changes were not assessed in this study.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Diamond, Barnett, Thomas, & Munro, 2007 source

      Not checked in the free run.

    • Rests on an assumption: Early childhood is the period of greatest neural plasticity.

  • May combine two claims.

    Premisecitation

    Brain development is non-linear and progresses in a localized, region-specific manner that coincides with functional maturation.

    “Nevertheless, brain development is non-linear, and progresses in a localized and region-specific manner that coincides with functional maturation (Huttenlocher & Dabholkar, 1997; Keshavan, Anderson, & Pettegrew, 1994).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Huttenlocher & Dabholkar, 1997

      Not checked in the free run.

    • cites Keshavan, Anderson, & Pettegrew, 1994

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Many children with ADHD have difficulties with EFs; improved EF over development should reduce severity of ADHD symptoms and impairments.

    “This intervention is relevant to ADHD given the noted difficulties that many children with ADHD have with EFs (Doyle, 2006; Willcutt et al., 2005) and the notion that improved EF over development should reduce the severity of ADHD symptoms and impairments (Halperin and Schulz, 2006).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Doyle, 2006

      Not checked in the free run.

    • cites Willcutt et al., 2005 source

      Not checked in the free run.

    • cites Halperin and Schulz, 2006 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Physically and cognitively demanding play in a social setting can be used to develop social skills.

    “In addition, physically and cognitively demanding play within a social context can be used to mold and develop social skills and, when structured in the appropriate manner, can potentially enhance cognitive and behavioral development, and neural growth.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The proposed intervention would foster the maturation of numerous cortical areas and the functions tied to them.

    “Rather, it would facilitate development and growth of a wide array of cortical regions and their associated functions, which in turn, would allow for the implementation of compensatory mechanisms that have the potential to improve functioning in individuals with the disorder.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    When structured appropriately, physically and cognitively demanding play might improve cognitive, behavioral, and neural development.

    “In addition, physically and cognitively demanding play within a social context can be used to mold and develop social skills and, when structured in the appropriate manner, can potentially enhance cognitive and behavioral development, and neural growth.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    Compliance may be less of a problem for the proposed play intervention than for more effortful and less palatable interventions.

    “As compared to other more effortful and less palatable interventions, compliance may be less of a problem with such an intervention.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Interpretationcitation

    Engaging children in sports, nature, and other group-based cognitively and physically challenging activities could offer a route to neural and cognitive growth that might reduce ADHD severity across development.

    “In addition, beyond directed play and exercises with parents, it is possible that engaging children in sports, nature (Kuo & Taylor, 2004), and other group-based cognitively and physically challenging activities may provide an avenue for neural and cognitive growth that would serve to facilitate the diminution of ADHD severity across development.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kuo & Taylor, 2004

      Not checked in the free run.

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

    Interpretationreasoning

    Many common children's games, activities, and exercises are easy for families to play together and engage wide-ranging brain areas, targeting the diffuse neurocognitive deficits associated with ADHD.

    “There are numerous common children’s games, activities and exercises that would be easy for families to play together and involve the use of wide ranging brain areas, targeting the diffuse neurocognitive deficits that have been associated with ADHD.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: ADHD is associated with diffuse neurocognitive deficits.
    • Rests on an assumption: Common children's games engage specific neurocognitive functions such as inhibitory control, working memory, and motor control.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Because play is intrinsically rewarding, it is an ideal way to deliver treatment to children with ADHD.

    “In particular, the intrinsic rewarding qualities of play (i.e., it’s fun) makes it an ideal delivery system for treatment of children with ADHD, who are known to be highly responsive to continuously rewarding contingencies; yet highly resistant to more effortful and less rewarding (i.e., less fun) tasks.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Children with ADHD are highly responsive to continuously rewarding contingencies.
    • Rests on an assumption: Children with ADHD are highly resistant to effortful and less rewarding tasks.
    • Rests on an assumption: Play is intrinsically rewarding or fun.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Directed play that combines cognitive challenges with physical exercise may be a viable treatment vehicle for children with ADHD.

    “Thus the creative use of directed play, which incorporates cognitive challenges and physical exercise, may have the potential to serve as a vehicle for treatment of children with ADHD.”
    Quote in the paperSubstantial claim
69 of 69

  • The paper relies on this without support.

    Continued treatment for ADHD throughout the lifetime is costly and problematic for logistical reasons.

    “The need for continued treatment throughout the lifetime is both costly and problematic for a number of logistical reasons.”

  • The paper relies on this without support.

    Findings from animal research on environmental enrichment and neurodevelopmental processes generalize to humans with ADHD.

    “a distinct scientific literature, largely consisting of research with animals, indicates that an array of neurodevelopmental processes facilitate efficient neurotransmission and are highly responsive to environmental influences.”

  • The paper relies on this without support.

    Findings from animal models of neurodevelopment and neurodevelopmental disorders generalize to humans, particularly children with ADHD.

    “Thus, literature in children is sparse, but the extensive body of animal research suggests that environmental enrichment and early brain rehabilitation could play a key role in the treatment, and possibly even the amelioration, of ADHD symptomatology through improving the core neural deficits associated with the disorder.”

  • The paper relies on this without support.

    Early childhood is the period of greatest neural plasticity.

    “Although early childhood is the period of greatest neural plasticity, and the most prominent cell proliferation in response to exercise has been shown to occur at younger ages in rats (Kim et al., 2004), far less research has been conducted with children.”

  • The paper relies on this without support.

    Children with ADHD are highly responsive to continuously rewarding contingencies.

    “who are known to be highly responsive to continuously rewarding contingencies; yet highly resistant to more effortful and less rewarding (i.e., less fun) tasks.”

  • The paper relies on this without support.

    Children with ADHD are highly resistant to effortful and less rewarding tasks.

    “who are known to be highly responsive to continuously rewarding contingencies; yet highly resistant to more effortful and less rewarding (i.e., less fun) tasks.”

  • The paper relies on this without support.

    ADHD is associated with diffuse neurocognitive deficits.

    “targeting the diffuse neurocognitive deficits that have been associated with ADHD.”

  • The paper relies on this without support.

    ADHD is caused by a core neural pathology.

    “the core neural pathology that causes ADHD.”

  • The paper relies on this without support.

    Play is intrinsically rewarding or fun.

    “the intrinsic rewarding qualities of play (i.e., it’s fun)”

  • The paper relies on this without support.

    Common children's games engage specific neurocognitive functions such as inhibitory control, working memory, and motor control.

    “For example, the game “S]imon-says” involves inhibitory control, “my grandmother went to the market” involves working memory, and “hopscotch” involves physical exercise and requires motor control.”
10 of 10

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • A mouse study is described as a rat study

    Minor

    The text attributes the cited dentate-gyrus finding to experiments in rats, but its reference identifies the subjects as adult mice.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. Chronis, 2001, Comprehensive, sustained behavioral and pharmacological treatment for attention-deficit/hyperactivity disorder: a case study, Behav. Therapy, 8, 346
  2. Hebb, D.O., 1949. The Organization of Behavior: A Neuropsychological Theory. Wiley, New York, p. 335.
  3. Rapport, 1996, Methylphenidate and attentional training. Comparative effects on behavior and neurocognitive performance in twin girls with attention-deficit/hyperactivity disorder, Behav. Modif., 20, 428, 10.1177/01454455960204004 · DOI
  4. Ravaglia, 2008, Physical activity and dementia risk in the elderly: findings from a prospective Italian study, Neurology, 70, 1786, 10.1212/01.wnl.0000296276.50595.86 · DOI
  5. Weiss, 2006, Effectiveness outcomes in attention-deficit/hyperactivity disorder, J. Clin. Psychiatry, 67, 38

Cited by

Sorted by citations

Authors
Halperin, J. M., & Healey, D. M.
Affiliations
  • Queens College, CUNY (US)
  • University of Otago (NZ)
Corresponding author
Halperin, Jeffrey M.
ORCID
Halperin, Jeffrey M.
Venue
Neuroscience & Biobehavioral Reviews
Publisher
Elsevier BV
Published
2011-01
Volume
35
Issue
3
Pages
621-634
ISSN
0149-7634 (ISSN-L)
DOI
10.1016/j.neubiorev.2010.07.006
PMC
PMC3008505
OpenAlex
W1989027174
Semantic Scholar
bbb85d7be5c6a8d10df9f9b43e790f9b61f5a0fa
Cited by
237
References
262
Citations by year
2026: 11 · 2025: 13 · 2024: 8 · 2023: 9 · 2022: 9 · 2021: 17 · 2020: 12 · 2019: 17 · 2018: 14 · 2017: 12 · 2016: 17 · 2015: 18 · 2014: 27 · 2013: 16 · 2012: 23
FWCI
2.32
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuroscience & Biobehavioral Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R21MH085898, R01 MH068286)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Developmental and Educational Neuropsychology
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Keywords
attention deficit hyperactivity disorder, environmental enrichment, cognitive enhancement, physical activity, brain development, developmental trajectories
MeSH terms
Attention Deficit Disorder with Hyperactivity, Brain, Environment, Humans, Exercise, Nootropic Agents

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.

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