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Cited by 196Physical Activity and HealthCardiovascular and exercise physiologyCognitive Functions and Memory

Dose-Response Matters! - A Perspective on the Exercise Prescription in Exercise-Cognition Research

Open access
Herold, Fabian, Müller, Patrick, Gronwald, Thomas, Müller, Notger G.·2019·Frontiers in Psychology
DOI 10.3389/fpsyg.2019.02338PMC PMC6839278
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Abstract

In general, it is well recognized that both acute physical exercises and regular physical training influence brain plasticity and cognitive functions positively. However, growing evidence shows that the same physical exercises induce very heterogeneous outcomes across individuals. In an attempt to better understand this interindividual heterogeneity in response to acute and regular physical exercising, most research, so far, has focused on non-modifiable factors such as sex and different genotypes, while relatively little attention has been paid to exercise prescription as a modifiable factor. With an adapted exercise prescription, dosage can be made comparable across individuals, a procedure that is necessary to better understand the dose-response relationship in exercise-cognition research. This improved understanding of dose-response relationships could help to design more efficient physical training approaches against, for instance, cognitive decline.

AI snapshot

Written from the paper’s full text.

TL;DR

This perspective argues that interindividual heterogeneity in exercise–cognition outcomes is partly attributable to how exercise dose is prescribed and operationalized. It proposes defining dose via specific marker(s) of internal load—such as peripheral blood lactate—so that adapted exercise prescriptions can provide comparable doses across individuals and potentially reduce neurocognitive response heterogeneity.

Key findings

  • The paper proposes that “dose” should be operationalized using a specific marker or markers of internal load, rather than external load alone, because internal load reflects the individual acute psychophysiological response that triggers neurobiological processes.
  • Peripheral blood lactate is highlighted as a promising internal-load marker: it can cross the blood–brain barrier and provide energy to the brain, and relative changes in peripheral blood lactate are reported to correlate significantly with cognitive performance after high-intensity interval endurance exercises and with peripheral serum BDNF levels.
  • Traditional exercise prescriptions using fixed percentages of maximal oxygen uptake or heart rate are said to produce considerable interindividual heterogeneity in other internal-load markers such as peripheral blood lactate, which may contribute to heterogeneous neurocognitive outcomes.
  • Examples cited include changes in cardiorespiratory fitness after a 21-week combined exercise intervention in older adults ranging from −8 to 42%, and after 6 weeks of high-intensity endurance training, responders who improved VO2peak more than non-responders showed a significantly higher increase in serum BDNF.

Methods

  • Design: Perspective/theoretical article; no empirical study, dataset, or sample is reported.
  • Data or sample: Not stated in the paper; the article synthesizes and discusses existing literature rather than presenting original data.
  • Main analysis: Conceptual synthesis and proposal of definitions, tables, and a framework for exercise prescription, dose, internal load, and responder/non-responder classification in exercise–cognition research.

Limitations

  • Stated in the paper: the assumptions are “mostly theoretical in nature,” and further research comparing traditional versus adapted exercise prescriptions with regard to neuroplasticity and cognition is urgently needed.
  • Stated in the paper: other exercise-related factors such as movement frequency (e.g., cycling cadence) and psychological factors such as affective response (e.g., enjoyment or expectations) were not considered.
  • Stated in the paper: lactate monitoring requires blood sampling and a graded exercise test to calculate an individual threshold; the optimal internal-load marker for neuroplasticity and cognition has yet to be discovered.
  • Evident from the text: the proposed dose–response framework is not empirically tested in this article, and the cited associations between cardiorespiratory fitness, brain measures, and cognition are described as “not strictly causal in nature.”

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

Integrity signals

Registry

Crossref · 10.3389/fpsyg.2019.02338

Cites

317 of 317 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 118 cited sources checked · 0 supported · 0 flagged

  • Premisenone given

    Most research on interindividual heterogeneity in response to acute and regular physical exercising has focused on non-modifiable factors such as sex and different genotypes, while relatively little attention has been paid to exercise prescription as a modifiable factor.

    “In an attempt to better understand this interindividual heterogeneity in response to acute and regular physical exercising, most research, so far, has focused on non-modifiable factors such as sex and different genotypes, while relatively little attention has been paid to exercise prescription as a modifiable factor.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Gronwald et al., 2018b

      Not checked in the free run.

    • cites Gronwald et al., 2019a

      Not checked in the free run.

    • cites Suwabe et al., 2018 source

      Not checked in the free run.

  • Interpretationnone given

    Interindividual heterogeneity in response to acute physical exercise and/or physical training might contribute to the interindividual heterogeneity observed in neurocognitive outcomes.

    “Regardless of the ongoing discussion about how to classify the level of responsiveness, there is some evidence that the interindividual heterogeneity in response to acute physical exercise and/or physical training might contribute to the interindividual heterogeneity observed in neurocognitive outcomes.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    The same physical exercises induce very heterogeneous outcomes across individuals.

    “However, growing evidence shows that the same physical exercises induce very heterogeneous outcomes across individuals.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Katch et al., 1982 source

      Not checked in the free run.

    • cites Coggan and Costill, 1984

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    • cites Bagger et al., 2003 source

      Not checked in the free run.

  • Premisecitation

    Not all scientific disciplines investigating exercise-cognition are taking the issue of optimal exercise prescription parameters into account sufficiently.

    “Notably, what parameters are optimal to prescribe the best exercise for an individual is extensively discussed in the literature (Katch et al., 1978; Weltman et al., 1989, 1990; Gass et al., 1991; Meyer et al., 1999; Hofmann and Tschakert, 2010; Scharhag-Rosenberger et al., 2010; Mann et al., 2013; Weatherwax et al., 2016), but not all scientific disciplines investigating exercise–cognition are ta”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Gronwald et al., 2018b

      Not checked in the free run.

    • cites Gronwald et al., 2019a

      Not checked in the free run.

    • cites Suwabe et al., 2018 source

      Not checked in the free run.

  • Premisecitation

    All scientific disciplines studying the relationship between physical exercises and/or physical training and the central nervous system are based on an appropriate exercise prescription that specifies exercise and/or training variables.

    “Although these different scientific disciplines use different approaches to understand the relationship between physical exercises and/or physical training and the central nervous system, it is undoubted that all of them are based on an appropriate exercise prescription that specifies exercise (e.g., exercise intensity, exercise duration) and/or training variables (e.g., frequency of training ses”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Lightfoot, 2008 source

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    • cites Williams et al., 2019 source

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  • May combine two claims. 14
  • Classified as probably not a substantial claim. 13

  • May combine two claims.

    Premisecitation

    Exercise prescription is the key for dosing and for individualization of acute physical exercises and physical training.

    “Furthermore, exercise prescription is the key for dosing (Wasfy and Baggish, 2016; Pontifex et al., 2018) and for individualization of acute physical exercises and physical training (Lightfoot, 2008).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Wasfy and Baggish, 2016

      Not checked in the free run.

    • cites Pontifex et al., 2018 source

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    • cites Lightfoot, 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Acute physical exercises and regular physical training positively influence brain plasticity and cognitive functions.

    “In general, it is well recognized that both acute physical exercises and regular physical training influence brain plasticity and cognitive functions positively.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Chang et al., 2012a

      Not checked in the free run.

    • cites Colcombe et al., 2006 source

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    • cites Erickson et al., 2011 source

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  • May combine two claims.

    Premisecitation

    There is considerable within-individual and between-individual heterogeneity in acute psychophysiological responses to the same acute physical exercises and in long-term adaptations to the same physical training.

    “Since every human is unique, there is a considerable amount of within-individual (intra-individual) (Katch et al., 1982; Coggan and Costill, 1984; Bagger et al., 2003; Skurvydas et al., 2010; Faude et al., 2017; Chrzanowski-Smith et al., 2019; Voisin et al., 2019) and between-individual (interindividual) heterogeneity (Karavirta et al., 2011; Chmelo et al., 2015; Bonafiglia et al., 2016; Greenham”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Katch et al., 1982 source

      Not checked in the free run.

    • cites Karavirta et al., 2011 source

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    • cites Chmelo et al., 2015 source

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

    Interpretationreasoning

    Making dosage comparable across individuals is necessary to better understand the dose-response relationship in exercise-cognition research.

    “With an adapted exercise prescription, dosage can be made comparable across individuals, a procedure that is necessary to better understand the dose–response relationship in exercise–cognition research.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    Improved understanding of dose-response relationships could help to design more efficient physical training approaches against cognitive decline.

    “This improved understanding of dose–response relationships could help to design more efficient physical training approaches against, for instance, cognitive decline.”
    Quote in the paperNot a substantial claim

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

    Interpretationnone given

    With an adapted exercise prescription, dosage can be made comparable across individuals.

    “With an adapted exercise prescription, dosage can be made comparable across individuals, a procedure that is necessary to better understand the dose–response relationship in exercise–cognition research.”
    Quote in the paperNot a substantial claim

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

    Interpretationcitation

    Distinguishing and using the terms physical activity, physical exercise, and physical training carefully allows a better classification and interpretation of observed effects and of the underlying neurobiological mechanisms.

    “In essence, distinguishing and using these terms carefully allows a better classification and interpretation of observed effects and of the underlying (neuro)biological mechanisms (Budde et al., 2016).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Budde et al., 2016 source

      Not checked in the free run.

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

    Interpretationreasoning

    Internal load can be adjusted by modifying the external load.

    “According to the definition of internal load, which states that internal load is characterized by the individual and acute psychophysiological response(s) to the external load, it appears that internal load can be adjusted by modifying the external load.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    There is ongoing vivid discussion on how to define critical thresholds for responders and non-responders and whether further subgroups should be established.

    “There is ongoing vivid discussion on how to define these critical thresholds (Atkinson and Batterham, 2015; Swinton et al., 2018; Atkinson et al., 2019; Dankel and Loenneke, 2019) and whether further subgroups should be established (Dankel and Loenneke, 2019).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Atkinson and Batterham, 2015

      Not checked in the free run.

    • cites Swinton et al., 2018 source

      Not checked in the free run.

    • cites Dankel and Loenneke, 2019

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Brain-derived neurotrophic factor plays an important role in neuroplasticity and cognition.

    “which play an important role in neuroplasticity (Erickson et al., 2010, 2011; Brigadski and Leßmann, 2014) and cognition (Erickson et al., 2010; Brigadski and Leßmann, 2014; Leckie et al., 2014).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Erickson et al., 2010 source

      Not checked in the free run.

    • cites Brigadski and Leßmann, 2014

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    • cites Leckie et al., 2014 source

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  • May combine two claims.

    Interpretationcitation

    Not only peripheral systems are affected by the individual responsiveness state but also the central nervous system itself.

    “This finding suggests that not only peripheral systems are affected by the individual responsiveness state but also the central nervous system itself.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Measurement errors are inevitable in repeated measurements and are caused by random biological fluctuations that do not represent a meaningful change in the outcome variable.

    “(ii) measurement errors are inevitable in repeated measurements and are caused, for instance, by random biological fluctuations that do not represent a meaningful change in the outcome variable (Atkinson and Nevill, 1998; Scharhag-Rosenberger et al., 2012; Atkinson and Batterham, 2015; Williamson et al., 2017; Pickering and Kiely, 2019a)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Atkinson and Nevill, 1998

      Not checked in the free run.

    • cites Scharhag-Rosenberger et al., 2012 source

      Not checked in the free run.

    • cites Atkinson and Batterham, 2015

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dose is an essential factor for triggering neurobiological processes, such as release of neurotrophins including BDNF, which in turn lead to neuroplastic changes.

    “Since dose is an essential factor for triggering neurobiological processes (e.g., release of neurotrophins such as BDNF; Dinoff et al., 2017), which in turn lead to neuroplastic”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Dinoff et al., 2017 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Reduced levels of serum BDNF are related to a decline in hippocampal volume and poorer memory performance.

    “reduced levels of serum BDNF are related to a decline in hippocampal volume and poorer memory performance (Erickson et al., 2010)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Erickson et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Peripheral blood lactate can cross the blood-brain barrier and provides energy to the brain.

    “peripheral blood lactate (e.g., from muscles) can cross the blood–brain barrier and provides energy to the brain”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Kemppainen et al., 2005 source

      Not checked in the free run.

    • cites Quistorff et al., 2008 source

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    • cites van Hall et al., 2009 source

      Not checked in the free run.

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

    Interpretationcitation

    It is more promising to use a marker or markers of internal load related to changes in neurotrophic molecules to individualize and adjust exercise prescription.

    “Hence, it seems more promising to use a marker or markers of internal load that are related to changes in neurotrophic molecules in order to individualize and adjust exercise prescription (Pedersen, 2019).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pedersen, 2019 source

      Not checked in the free run.

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

    Interpretationreasoning

    Using markers of internal load to prescribe exercise intensity is preferable to using parameters of external load such as speed in running specific exercises.

    “using markers of internal load to prescribe exercise intensity is preferable instead of using parameters of external load such as speed in running specific exercises.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Internal load is a better proxy for dose than external load.

  • May combine two claims.

    Premisecitation

    There is large interindividual heterogeneity in psychophysiological responses to acute physical exercises and in long-term adaptations to physical training.

    “Based on the large interindividual heterogeneity (i) in psychophysiological responses to acute physical exercises and (ii) in long-term adaptions to a physical training”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Buford and Pahor, 2012 source

      Not checked in the free run.

    • cites Buford et al., 2013 source

      Not checked in the free run.

    • cites Müller et al., 2017, 2018

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    HRV is an interesting marker of internal load because internal load quantification by HRV indices is progressive and takes individual fitness level, daily readiness, and actual health state into account.

    “HRV, i.e., the beat-to-beat variation over a distinct time period, under rest conditions or while exercising is an interesting marker of internal load because the internal load quantification by HRV indices is progressive and takes the individual fitness level as well as daily readiness and actual health state into account”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Thayer et al., 2012 source

      Not checked in the free run.

    • cites Plews et al., 2013 source

      Not checked in the free run.

    • cites Vesterinen et al., 2013, 2016

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    The neurotrophic hypothesis posits that in response to physical exercises, the organism releases neurochemicals such as BDNF, which trigger neuroplasticity and facilitate cognitive enhancement.

    “the “neurotrophic hypothesis,” which posits that in response to physical exercises, the organism releases several neurochemicals (e.g., neurotrophic factors such as BDNF), which in turn trigger neuroplasticity and facilitate cognitive enhancement”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Voss et al., 2013b

      Not checked in the free run.

    • cites Basso and Suzuki, 2017 source

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    • cites Stimpson et al., 2018 source

      Not checked in the free run.

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

    Premisecitation

    The exact molecular mechanisms of increased BDNF production in response to physical exercising are not fully understood.

    “the exact molecular mechanisms of increased BDNF production in response to physical exercising are not fully understood (for review, see Jiménez-Maldonado et al., 2018)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Jiménez-Maldonado et al., 2018 source

      Not checked in the free run.

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

    Premisecitation

    BDNF in the brain is involved in neuroplasticity.

    “BDNF in the brain is involved in neuroplasticity (Brigadski and Leßmann, 2014)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Brigadski and Leßmann, 2014

      Not checked in the free run.

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

    Interpretationreasoning

    The use of peripheral blood lactate as a proxy for dose seems a reasonable starting point.

    “the use of peripheral blood lactate as a proxy for dose seems a reasonable starting point.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Peripheral blood lactate levels are easily quantifiable by portable devices.

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

    Interpretationnone given

    Lactate monitoring necessitates blood sampling, which could be impractical in daily practice.

    “it necessitates blood sampling, which could be impractical in daily practice”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    BDNF release is influenced by several other non-modifiable factors, such as sex, or non-exercise-related modifiable factors, such as sleep or nutrition, that are known to influence neuroplasticity in general.

    “BDNF release is also influenced by several other non-modifiable (e.g., sex Trajkovska et al., 2007; Komulainen et al., 2010; Bus et al., 2011) or non-exercise-related modifiable factors (e.g., sleep or nutrition; Giese et al., 2013, 2014; Walsh et al., 2015; Schmitt et al., 2016) that are known to influence neuroplasticity in general”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Trajkovska et al., 2007 source

      Not checked in the free run.

    • cites Komulainen et al., 2010 source

      Not checked in the free run.

    • cites Bus et al., 2011 source

      Not checked in the free run.

25 of 25

  • The authors state this as an assumption.

    Non-responsiveness can best be counteracted by modifying the dose of the physical exercise and/or physical training.

    “Moreover, it is assumed that non-responsiveness can best be counteracted by modifying the dose of the physical exercise and/or physical training (Churchward-Venne et al., 2015; Ross et al., 2015; Montero and Lundby, 2017; Toigo, 2019).”

  • The authors state this as an assumption.

    Internal load is a better proxy for dose than external load.

    “it seems reasonable to assume that internal load is a better proxy for dose than external load.”

  • The authors state this as an assumption.

    Tailoring exercise to the characteristics and needs of a particular person is well suited to maximize its efficiency.

    “it is assumed that tailoring of these to the characteristics and needs of a particular person is well suited to maximize their efficiency”

  • The paper relies on this without support.

    Peripheral blood lactate levels are easily quantifiable by portable devices.

    “peripheral blood lactate levels are easily quantifiable by portable devices”
4 of 4

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

Research works printed but not linked: 2

  1. McMorris, Exercise–cognition interaction: state of the art and future research, Exercise-Cognition Interaction, 459
  2. Robergs, 2002, The surprising history of the “HRmax=220-age” equiation., J. Exerc. Physiol., 5, 1

Cited by

Sorted by citations

Related

Authors
Herold, F., Müller, P., Gronwald, T., & Müller, N. G.
Affiliations
  • German Center for Neurodegenerative Diseases (DE)
  • MSH Medical School Hamburg – University of Applied Sciences and Medical University (DE)
Corresponding author
Herold, Fabian
ORCID
Venue
Frontiers in Psychology
Publisher
Frontiers Media SA
Published
2019-11-01
Volume
10
Pages
2338-2338
ISSN
1664-1078 (ISSN-L)
DOI
10.3389/fpsyg.2019.02338
PMC
PMC6839278
OpenAlex
W2989185040
Cited by
196
References
317
Citations by year
2026: 26 · 2025: 33 · 2024: 27 · 2023: 26 · 2022: 31 · 2021: 29 · 2020: 18 · 2019: 4 · 2018: 2
FWCI
14.06
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Psychology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DZNE Pub (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Physiology › Physical Activity and Health
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Functions and Memory
Keywords
exercise prescription, dose-response relationship, individual heterogeneity, acute exercise, exercise training, neuroplasticity, cognitive function, cognitive decline, modifiable factors

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