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Is impaired dopaminergic function associated with mobility capacity in older adults?

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Abstract

The capacity to move is essential for independence and declines with age. Slow movement speed, in particular, is strongly associated with negative health outcomes. Prior research on mobility (herein defined as movement slowness) and aging has largely focused on musculoskeletal mechanisms and processes. More recent work has provided growing evidence for a significant role of the nervous system in contributing to reduced mobility in older adults. In this article, we report four pieces of complementary evidence from behavioral, genetic, and neuroimaging experiments that, we believe, provide theoretical support for the assertion that the basal ganglia and its dopaminergic function are responsible, in part, for age-related reductions in mobility. We report four a posteriori findings from an existing dataset: (1) slower central activation of ballistic force development is associated with worse mobility among older adults; (2) older adults with the Val/Met intermediate catecholamine-O-methyl-transferase (COMT) genotype involved in dopamine degradation exhibit greater mobility than their homozygous counterparts; (3) there are moderate relationships between performance times from a series of lower and upper extremity tasks supporting the notion that movement speed in older adults is a trait-like attribute; and (4) there is a relationship of functional connectivity within the medial orbofrontal (mOFC) cortico-striatal network and measures of mobility, suggesting that a potential neural mechanism for impaired mobility with aging is the deterioration of the integrity of key regions within the mOFC cortico-striatal network. These findings align with recent basic and clinical science work suggesting that the basal ganglia and its dopaminergic function are mechanistically linked to age-related reductions in mobility capacity.

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References

  1. Organization), W.W.H. Ageing and health. 2018 [cited 2020 September 15]; Available from: https://www.who.int/news-room/fact-sheets/detail/ageing-and-health.

  2. Studenski S, Perera S, Patel K, Rosano C, Faulkner K, Inzitari M, et al. Gait speed and survival in older adults. JAMA. 2011;305(1):50–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Cummings SR, Studenski S, Ferrucci L. A diagnosis of dismobility--giving mobility clinical visibility: a mobility working group recommendation. JAMA. 2014;311(20):2061–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Musich S, Wang SS, Ruiz J, Hawkins K, Wicker E. The impact of mobility limitations on health outcomes among older adults. Geriatr Nurs. 2018;39(2):162–9.

    PubMed  Google Scholar 

  5. Shumway-Cook A, Ciol MA, Yorkston KM, Hoffman JM, Chan L. Mobility limitations in the Medicare population: prevalence and sociodemographic and clinical correlates. J Am Geriatr Soc. 2005;53(7):1217–21.

    PubMed  Google Scholar 

  6. Vermeulen J, Neyens JCL, van Rossum E, Spreeuwenberg MD, de Witte LP. Predicting ADL disability in community-dwelling elderly people using physical frailty indicators: a systematic review. BMC Geriatr. 2011;11:33.

    PubMed  PubMed Central  Google Scholar 

  7. Cawthon PM, Fox KM, Gandra SR, Delmonico MJ, Chiou CF, Anthony MS, et al. Do muscle mass, muscle density, strength, and physical function similarly influence risk of hospitalization in older adults? J Am Geriatr Soc. 2009;57(8):1411–9.

    PubMed  PubMed Central  Google Scholar 

  8. Newman AB, Simonsick EM, Naydeck BL, Boudreau RM, Kritchevsky SB, Nevitt MC, et al. Association of long-distance corridor walk performance with mortality, cardiovascular disease, mobility limitation, and disability. JAMA. 2006;295(17):2018–26.

    CAS  PubMed  Google Scholar 

  9. Gill TM, Allore HG, Hardy SE, Guo Z. The dynamic nature of mobility disability in older persons. J Am Geriatr Soc. 2006;54(2):248–54.

    PubMed  Google Scholar 

  10. Simonsick EM, Newman AB, Visser M, Goodpaster B, Kritchevsky SB, Rubin S, et al. Mobility limitation in self-described well-functioning older adults: importance of endurance walk testing. J Gerontol A Biol Sci Med Sci. 2008;63(8):841–7.

    PubMed  PubMed Central  Google Scholar 

  11. Hardy SE, Kang Y, Studenski SA, Degenholtz HB. Ability to walk 1/4 mile predicts subsequent disability, mortality, and health care costs. J Gen Intern Med. 2011;26(2):130–5.

    PubMed  Google Scholar 

  12. Manini TM, Visser M, Won-Park S, Patel KV, Strotmeyer ES, Chen H, et al. Knee extension strength cutpoints for maintaining mobility. J Am Geriatr Soc. 2007;55(3):451–7.

    PubMed  Google Scholar 

  13. Bhasin S et al. Sarcopenia Definition: The Position Statements of the Sarcopenia Definition and Outcomes Consortium. J Am Geriatr Soc, 2020.

  14. Reid KF, Naumova EN, Carabello RJ, Phillips EM, Fielding RA. Lower extremity muscle mass predicts functional performance in mobility-limited elders. J Nutr Health Aging. 2008;12(7):493–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Wages NP, Simon JE, Clark LA, Amano S, Russ DW, Manini TM, et al. Relative contribution of muscle strength, lean mass, and lower extremity motor function in explaining between-person variance in mobility in older adults. BMC Geriatr. 2020;20(1):255.

    PubMed  PubMed Central  Google Scholar 

  16. Holtzer R, Epstein N, Mahoney JR, Izzetoglu M, Blumen HM. Neuroimaging of mobility in aging: a targeted review. J Gerontol A Biol Sci Med Sci. 2014;69(11):1375–88.

    PubMed  PubMed Central  Google Scholar 

  17. Sorond FA, Cruz-Almeida Y, Clark DJ, Viswanathan A, Scherzer CR, de Jager P, et al. Aging, the central nervous system, and mobility in older adults: neural mechanisms of mobility impairment. J Gerontol A Biol Sci Med Sci. 2015;70(12):1526–32.

    PubMed  PubMed Central  Google Scholar 

  18. Varma VR, Hausdorff JM, Studenski SA, Rosano C, Camicioli R, Alexander NB, et al. Aging, the central nervous system, and mobility in older adults: interventions. J Gerontol A Biol Sci Med Sci. 2016;71(11):1451–8.

    PubMed  PubMed Central  Google Scholar 

  19. Rosso AL, Studenski SA, Chen WG, Aizenstein HJ, Alexander NB, Bennett DA, et al. Aging, the central nervous system, and mobility. J Gerontol A Biol Sci Med Sci. 2013;68(11):1379–86.

    PubMed  PubMed Central  Google Scholar 

  20. Balleine BW, Liljeholm M, Ostlund SB. The integrative function of the basal ganglia in instrumental conditioning. Behav Brain Res. 2009;199(1):43–52.

    PubMed  Google Scholar 

  21. Dudman JT, Krakauer JW. The basal ganglia: from motor commands to the control of vigor. Curr Opin Neurobiol. 2016;37:158–66.

    CAS  PubMed  Google Scholar 

  22. Deniau JM, et al. The pars reticulata of the substantia nigra: a window to basal ganglia output. Prog Brain Res. 2007;160:151–72.

    CAS  PubMed  Google Scholar 

  23. Parent A. Extrinsic connections of the basal ganglia. Trends Neurosci. 1990;13(7):254–8.

    CAS  PubMed  Google Scholar 

  24. Berardelli A, et al. Pathophysiology of bradykinesia in Parkinson's disease. Brain. 2001;124(Pt 11):2131–46.

    CAS  PubMed  Google Scholar 

  25. Buhusi CV, Meck WH. What makes us tick? Functional and neural mechanisms of interval timing. Nat Rev Neurosci. 2005;6(10):755–65.

    CAS  PubMed  Google Scholar 

  26. Turner RS, Desmurget M. Basal ganglia contributions to motor control: a vigorous tutor. Curr Opin Neurobiol. 2010;20(6):704–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Panigrahi B, Martin KA, Li Y, Graves AR, Vollmer A, Olson L, et al. Dopamine is required for the neural representation and control of movement vigor. Cell. 2015;162(6):1418–30.

    CAS  PubMed  Google Scholar 

  28. da Silva JA, Tecuapetla F, Paixão V, Costa RM. Dopamine neuron activity before action initiation gates and invigorates future movements. Nature. 2018;554(7691):244–8.

    PubMed  Google Scholar 

  29. Kaasinen V, Rinne JO. Functional imaging studies of dopamine system and cognition in normal aging and Parkinson's disease. Neurosci Biobehav Rev. 2002;26(7):785–93.

    CAS  PubMed  Google Scholar 

  30. Carlsson A, Winblad B. Influence of age and time interval between death and autopsy on dopamine and 3-methoxytyramine levels in human basal ganglia. J Neural Transm. 1976;38(3–4):271–6.

    CAS  PubMed  Google Scholar 

  31. Suhara T, Fukuda H, Inoue O, Itoh T, Suzuki K, Yamasaki T, et al. Age-related changes in human D1 dopamine receptors measured by positron emission tomography. Psychopharmacology. 1991;103(1):41–5.

    CAS  PubMed  Google Scholar 

  32. Wang Y, Chan GLY, Holden JE, Dobko T, Mak E, Schulzer M, et al. Age-dependent decline of dopamine D1 receptors in human brain: a PET study. Synapse. 1998;30(1):56–61.

    CAS  PubMed  Google Scholar 

  33. Rinne JO, Hietala J, Ruotsalainen U, Säkö E, Laihinen A, Någren K, et al. Decrease in human striatal dopamine D2 receptor density with age: a PET study with [11C]raclopride. J Cereb Blood Flow Metab. 1993;13(2):310–4.

    CAS  PubMed  Google Scholar 

  34. Wong DF, Young D, Wilson PD, Meltzer CC, Gjedde A. Quantification of neuroreceptors in the living human brain: III. D2-like dopamine receptors: theory, validation, and changes during normal aging. J Cereb Blood Flow Metab. 1997;17(3):316–30.

    CAS  PubMed  Google Scholar 

  35. Antonini A, Leenders KL. Dopamine D2 receptors in normal human brain: effect of age measured by positron emission tomography (PET) and [11C]-raclopride. Ann N Y Acad Sci. 1993;695:81–5.

    CAS  PubMed  Google Scholar 

  36. Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, MacGregor RR, et al. Measuring age-related changes in dopamine D2 receptors with 11C-raclopride and 18F-N-methylspiroperidol. Psychiatry Res. 1996;67(1):11–6.

    CAS  PubMed  Google Scholar 

  37. Stoessl AJ, Lehericy S, Strafella AP. Imaging insights into basal ganglia function, Parkinson's disease, and dystonia. Lancet. 2014;384(9942):532–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Rutherford BR, Choi J, Slifstein M, O'Boyle K, Abi-Dargham A, Brown PJ, et al. Neuroanatomical predictors of L-DOPA response in older adults with psychomotor slowing and depression: a pilot study. J Affect Disord. 2020;265:439–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Fahn S, Jankovic J, Hallett M. Principles and Practice of Movement Disorders. 2nd ed. 2011. New York: Elsevier Saunders.

  40. Pahwa R, Lyons KE, and Koller WC, Handbook of Parkinson’s Disease. 3rd ed. 2003, Boca Raton, Fl: Taylor and Francis Group.

  41. Malling ASB, Morberg BM, Wermuth L, Gredal O, Bech P, Jensen BR. Effect of transcranial pulsed electromagnetic fields (T-PEMF) on functional rate of force development and movement speed in persons with Parkinson's disease: a randomized clinical trial. PLoS One. 2018;13(9):e0204478.

    PubMed  PubMed Central  Google Scholar 

  42. Mazzoni P, Hristova A, Krakauer JW. Why don't we move faster? Parkinson's disease, movement vigor, and implicit motivation. J Neurosci. 2007;27(27):7105–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Rose MH, Løkkegaard A, Sonne-Holm S, Jensen BR. Tremor irregularity, torque steadiness and rate of force development in Parkinson's disease. Mot Control. 2013;17(2):203–16.

    Google Scholar 

  44. Hauber W. Impairments of movement initiation and execution induced by a blockade of dopamine D1 or D2 receptors are reversed by a blockade of N-methyl-D-aspartate receptors. Neuroscience. 1996;73(1):121–30.

    CAS  PubMed  Google Scholar 

  45. Del Vecchio A, et al. You are as fast as your motor neurons: speed of recruitment and maximal discharge of motor neurons determine the maximal rate of force development in humans. J Physiol. 2019;597(9):2445–56.

    PubMed  PubMed Central  Google Scholar 

  46. Liddell EGT and Sherrington CS, Recruitment and some factors of reflex inhibition. Proceedings of the Royal Society of London. B., 1925. 97: p. 488–518.

  47. Clark BC, Taylor JL, Hong SL, Law TD, Russ DW. Weaker seniors exhibit motor cortex hypoexcitability and impairments in voluntary activation. J Gerontol A Biol Sci Med Sci. 2015;70(9):1112–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Oh MM, Disterhoft JF. Learning and aging affect neuronal excitability and learning. Neurobiol Learn Mem. 2020;167:107133.

    PubMed  Google Scholar 

  49. Landfield PW, Pitler TA. Prolonged Ca2+−dependent afterhyperpolarizations in hippocampal neurons of aged rats. Science. 1984;226(4678):1089–92.

    CAS  PubMed  Google Scholar 

  50. Moyer JR Jr, Thompson LT, Black JP, Disterhoft JF. Nimodipine increases excitability of rabbit CA1 pyramidal neurons in an age- and concentration-dependent manner. J Neurophysiol. 1992;68(6):2100–9.

    CAS  PubMed  Google Scholar 

  51. Murphy GG, Fedorov NB, Giese KP, Ohno M, Friedman E, Chen R, et al. Increased neuronal excitability, synaptic plasticity, and learning in aged Kvbeta1.1 knockout mice. Curr Biol. 2004;14(21):1907–15.

    CAS  PubMed  Google Scholar 

  52. Christie A, Kamen G. Short-term training adaptations in maximal motor unit firing rates and after hyperpolarization duration. Muscle Nerve. 2010;41(5):651–60.

    PubMed  Google Scholar 

  53. Kalmar JM, Button DC, Gardiner K, Cahill F, Gardiner PF. Caloric restriction does not offset age-associated changes in the biophysical properties of motoneurons. J Neurophysiol. 2009;101(2):548–57.

    CAS  PubMed  Google Scholar 

  54. Christie A, Kamen G. Doublet discharges in motoneurons of young and older adults. J Neurophysiol. 2006;95(5):2787–95.

    PubMed  Google Scholar 

  55. Duchateau J, Baudry S. Maximal discharge rate of motor units determines the maximal rate of force development during ballistic contractions in human. Front Hum Neurosci. 2014;8:234.

    PubMed  PubMed Central  Google Scholar 

  56. Kamen G, Sison SV, du CC, Patten C. Motor unit discharge behavior in older adults during maximal-effort contractions. J Appl Physiol. 1995;79(6):1908–13.

    CAS  PubMed  Google Scholar 

  57. Kamen G, Knight CA. Training-related adaptations in motor unit discharge rate in young and older adults. J Gerontol A Biol Sci Med Sci. 2004;59(12):1334–8.

    PubMed  Google Scholar 

  58. Van Cutsem M, Duchateau J, Hainaut K. Changes in single motor unit behaviour contribute to the increase in contraction speed after dynamic training in humans. J Physiol. 1998;513(Pt 1):295–305.

    PubMed  PubMed Central  Google Scholar 

  59. Riwniak C, et al., Comparison of a multi-component physical function battery to usual walking speed for assessing lower extremity function and mobility limitation in older adults. J Nutr Health Aging, In Press.

  60. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics. 1996;6(3):243–50.

    CAS  PubMed  Google Scholar 

  61. Schacht JP. COMT val158met moderation of dopaminergic drug effects on cognitive function: a critical review. Pharm J. 2016;16(5):430–8.

    CAS  Google Scholar 

  62. Bilder RM, Volavka J, Lachman HM, Grace AA. The catechol-O-methyltransferase polymorphism: relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology. 2004;29(11):1943–61.

    CAS  PubMed  Google Scholar 

  63. Grace AA. Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience. 1991;41(1):1–24.

    CAS  PubMed  Google Scholar 

  64. Reppert TR, Rigas I, Herzfeld DJ, Sedaghat-Nejad E, Komogortsev O, Shadmehr R. Movement vigor as a traitlike attribute of individuality. J Neurophysiol. 2018;120(2):741–57.

    PubMed  PubMed Central  Google Scholar 

  65. Choi JE, Vaswani PA, Shadmehr R. Vigor of movements and the cost of time in decision making. J Neurosci. 2014;34(4):1212–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Bargary G, Bosten JM, Goodbourn PT, Lawrance-Owen AJ, Hogg RE, Mollon JD. Individual differences in human eye movements: an oculomotor signature? Vis Res. 2017;141:157–69.

    PubMed  Google Scholar 

  67. Shadmehr R, Reppert TR, Summerside EM, Yoon T, Ahmed AA. Movement vigor as a reflection of subjective economic utility. Trends Neurosci. 2019;42:323–36.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Salamone JD, Pardo M, Yohn SE, López-Cruz L, SanMiguel N, Correa M. Mesolimbic dopamine and the regulation of motivated behavior. Curr Top Behav Neurosci. 2016;27:231–57.

    PubMed  Google Scholar 

  69. Fettes P, Schulze L, Downar J. Cortico-striatal-thalamic loop circuits of the orbitofrontal cortex: promising therapeutic targets in psychiatric illness. Front Syst Neurosci. 2017;11:25.

    PubMed  PubMed Central  Google Scholar 

  70. Kringelbach ML. The human orbitofrontal cortex: linking reward to hedonic experience. Nat Rev Neurosci. 2005;6(9):691–702.

    CAS  PubMed  Google Scholar 

  71. Kringelbach ML, Rolls ET. The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology. Prog Neurobiol. 2004;72(5):341–72.

    PubMed  Google Scholar 

  72. Hogan PS, Galaro JK, Chib VS. Roles of ventromedial prefrontal cortex and anterior cingulate in subjective valuation of prospective effort. Cereb Cortex. 2018.

  73. Wilson J, Allcock L, Mc Ardle R, Taylor JP, Rochester L. The neural correlates of discrete gait characteristics in ageing: a structured review. Neurosci Biobehav Rev. 2019;100:344–69.

    PubMed  PubMed Central  Google Scholar 

  74. Russ DW, et al. Development of a neuromuscular electrical stimulation protocol for sprint training. Med Sci Sports Exerc. 2012;44:1810–9.

    PubMed  Google Scholar 

  75. Clark BC, Manini TM, Wages NP, Simon JE, Clark LA. Voluntary vs electrically stimulated activation in age-related muscle weakness. JAMA Netw Open. 2019;2(9):e1912052.

    PubMed  PubMed Central  Google Scholar 

  76. Maffiuletti NA, Aagaard P, Blazevich AJ, Folland J, Tillin N, Duchateau J. Rate of force development: physiological and methodological considerations. Eur J Appl Physiol. 2016;116(6):1091–116.

    PubMed  PubMed Central  Google Scholar 

  77. Tavoian D, Ampomah K, Amano S, Law TD, Clark BC. Changes in DXA-derived lean mass and MRI-derived cross-sectional area of the thigh are modestly associated. Sci Rep. 2019;9(1):10028.

    PubMed  PubMed Central  Google Scholar 

  78. Szymkowicz SM, et al. Associations between subclinical depressive symptoms and reduced brain volume in middle-aged to older adults. Aging Ment Health. 2018.

  79. Szymkowicz SM, Dotson VM, McLaren ME, de Wit L, O'Shea DM, Talty FT, et al. Precuneus abnormalities in middle-aged to older adults with depressive symptoms: an analysis of BDI-II symptom dimensions. Psychiarty Research: Neuroimaging. 2017;268:9–14.

    Google Scholar 

  80. Nissim, N.R., et al., Frontal structural neural correlates of working memory performance in older adults. Front Aging Neurosci, 2017

  81. McLaren ME, Szymkowicz SM, O'Shea A, Woods AJ, Anton SD, Dotson VM. Vertex-wise examination of symptom dimensions of subthreshold depression and brain volumes. Psychiatry Res. 2017;260:70–5.

    Google Scholar 

  82. O’Shea A, et al. Cognitive aging and the hippocampus in older adults. Front Aging Neurosci. 2016;8:298.

    PubMed  PubMed Central  Google Scholar 

  83. Seider T, et al. Cognitively engaging activity is associated with greater cortical and subcortical volume. Front Aging Neurosci. 2016;8:1–10.

    Google Scholar 

  84. Seider T, et al. Age exacerbates HIV associated white matter abnormalities. J Neuro-Oncol. 2016;22(2):201–12.

    Google Scholar 

  85. Szymkowicz SM, McLaren ME, O'Shea A, Woods AJ, Anton SD, Dotson VM. Depressive symptoms modify age effects on hippocampal subfields in older adults. Geriatr Gerontol Int. 2017;17(10):1494–500.

    PubMed  Google Scholar 

  86. Woods AJ, Hamilton RH, Kranjec A, Minhaus P, Bikson M, Yu J, et al. Space, time, and causality in the human brain. Neuroimage. 2014;92:285–97.

    PubMed  Google Scholar 

  87. Whitfield-Gabrieli S, Nieto-Castanon A. Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect. 2012;2(3):125–41.

    PubMed  Google Scholar 

  88. Behzadi Y, Restom K, Liau J, Liu TT. A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage. 2007;37(1):90–101.

    PubMed  Google Scholar 

  89. Xiao Y, Fonov V, Chakravarty MM, Beriault S, al Subaie F, Sadikot A, et al. A dataset of multi-contrast population-averaged brain MRI atlases of a Parkinsons disease cohort. Data Brief. 2017;12:370–9.

    PubMed  PubMed Central  Google Scholar 

  90. Prodoehl J, Yu H, Little DM, Abraham I, Vaillancourt DE. Region of interest template for the human basal ganglia: comparing EPI and standardized space approaches. Neuroimage. 2008;39(3):956–65.

    PubMed  Google Scholar 

  91. Schmidt P. Bayesian inference for structured additive regression models for large-scale problems with applications to medical imaging. , in LMU München: Fakultät für Mathematik, Informatik und Statistik. 2017.

  92. Schmidt P, Gaser C, Arsic M, Buck D, Förschler A, Berthele A, et al. An automated tool for detection of FLAIR-hyperintense white-matter lesions in multiple sclerosis. Neuroimage. 2012;59(4):3774–83.

    PubMed  Google Scholar 

  93. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol. 1995;57(1):289–300.

    Google Scholar 

  94. Clark DJ, et al. Muscle performance and physical function are associated with voluntary rate of neuromuscular activation in older adults. J Gerontol A Biol Sci Med Sci. 2011;66(1):115–21.

    PubMed  Google Scholar 

  95. Clark DJ, Manini TM, Fielding RA, Patten C. Neuromuscular determinants of maximum walking speed in well-functioning older adults. Exp Gerontol. 2013;48(3):358–63.

    PubMed  PubMed Central  Google Scholar 

  96. Farina D, Merletti R, Enoka RM. The extraction of neural strategies from the surface EMG. J Appl Physiol. 2004;96(4):1486–95.

    PubMed  Google Scholar 

  97. Farina D, Merletti R, Enoka RM. The extraction of neural strategies from the surface EMG: an update. J Appl Physiol (1985). 2014;117(11):1215–30.

    Google Scholar 

  98. Galvan A, Wichmann T. Pathophysiology of parkinsonism. Clin Neurophysiol. 2008;119(7):1459–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Baroni A, Benvenuti F, Fantini L, Pantaleo T, Urbani F. Human ballistic arm abduction movements: effects of L-dopa treatment in Parkinson's disease. Neurology. 1984;34(7):868–76.

    CAS  PubMed  Google Scholar 

  100. Cacace F, Mineo D, Viscomi MT, Latagliata EC, Mancini M, Sasso V, et al. Intermittent theta-burst stimulation rescues dopamine-dependent corticostriatal synaptic plasticity and motor behavior in experimental parkinsonism: possible role of glial activity. Mov Disord. 2017;32(7):1035–46.

    CAS  PubMed  Google Scholar 

  101. Hsieh TH, Huang YZ, Rotenberg A, Pascual-Leone A, Chiang YH, Wang JY, et al. Functional dopaminergic neurons in substantia nigra are required for transcranial magnetic stimulation-induced motor plasticity. Cereb Cortex. 2015;25(7):1806–14.

    PubMed  Google Scholar 

  102. Ghiglieri V, Pendolino V, Sgobio C, Bagetta V, Picconi B, Calabresi P. Theta-burst stimulation and striatal plasticity in experimental parkinsonism. Exp Neurol. 2012;236(2):395–8.

    PubMed  Google Scholar 

  103. Ko JH, Strafella AP. Dopaminergic neurotransmission in the human brain: new lessons from perturbation and imaging. Neuroscientist. 2012;18(2):149–68.

    CAS  PubMed  Google Scholar 

  104. Strafella AP, et al. Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain. 2003;126(Pt 12):2609–15.

    PubMed  Google Scholar 

  105. Monte-Silva K, Ruge D, Teo JT, Paulus W, Rothwell JC, Nitsche MA. D2 receptor block abolishes theta burst stimulation-induced neuroplasticity in the human motor cortex. Neuropsychopharmacology. 2011;36(10):2097–102.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Di Lazzaro V, et al. The physiological basis of the effects of intermittent theta burst stimulation of the human motor cortex. J Physiol. 2008;586(16):3871–9.

    PubMed  PubMed Central  Google Scholar 

  107. Holtzer R, Ozelius L, Xue X, Wang T, Lipton RB, Verghese J. Differential effects of COMT on gait and executive control in aging. Neurobiol Aging. 2010;31(3):523–31.

    CAS  PubMed  Google Scholar 

  108. Hupfeld KE, Vaillancourt DE, Seidler RD. Genetic markers of dopaminergic transmission predict performance for older males but not females. Neurobiol Aging. 2018;66:180 e11–21.

    Google Scholar 

  109. Metti AL, Rosano C, Boudreau R, Massa R, Yaffe K, Satterfield S, et al. Catechol-O-methyltransferase genotype and gait speed changes over 10 years in older adults. J Am Geriatr Soc. 2017;65(9):2016–22.

    PubMed  PubMed Central  Google Scholar 

  110. Meiser J, Weindl D, Hiller K. Complexity of dopamine metabolism. Cell Commun Signal. 2013;11(1):34.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Finberg JPM. Inhibitors of MAO-B and COMT: their effects on brain dopamine levels and uses in Parkinson's disease. J Neural Transm (Vienna). 2019;126(4):433–48.

    Google Scholar 

  112. Werkman TR, Glennon JC, Wadman WJ, McCreary A. Dopamine receptor pharmacology: interactions with serotonin receptors and significance for the aetiology and treatment of schizophrenia. CNS Neurol Disord Drug Targets. 2006;5(1):3–23.

    CAS  PubMed  Google Scholar 

  113. Zhang H, Sulzer D. Regulation of striatal dopamine release by presynaptic auto- and heteroreceptors. Basal Ganglia. 2012;2(1):5–13.

    PubMed  PubMed Central  Google Scholar 

  114. Eriksen J, Jorgensen TN, Gether U. Regulation of dopamine transporter function by protein-protein interactions: new discoveries and methodological challenges. J Neurochem. 2010;113(1):27–41.

    CAS  PubMed  Google Scholar 

  115. Mannisto PT, et al. Characteristics of catechol O-methyl-transferase (COMT) and properties of selective COMT inhibitors. Prog Drug Res. 1992;39:291–350.

    CAS  PubMed  Google Scholar 

  116. Mannisto PT, Kaakkola S. Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev. 1999;51(4):593–628.

    CAS  PubMed  Google Scholar 

  117. Matsumoto M, Weickert CS, Akil M, Lipska BK, Hyde TM, Herman MM, et al. Catechol O-methyltransferase mRNA expression in human and rat brain: evidence for a role in cortical neuronal function. Neuroscience. 2003;116(1):127–37.

    CAS  PubMed  Google Scholar 

  118. Cass WA, Zahniser NR, Flach KA, Gerhardt GA. Clearance of exogenous dopamine in rat dorsal striatum and nucleus accumbens: role of metabolism and effects of locally applied uptake inhibitors. J Neurochem. 1993;61(6):2269–78.

    CAS  PubMed  Google Scholar 

  119. Eisenhofer G, Kopin IJ, Goldstein DS. Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev. 2004;56(3):331–49.

    CAS  PubMed  Google Scholar 

  120. Sesack SR, Hawrylak VA, Matus C, Guido MA, Levey AI. Dopamine axon varicosities in the prelimbic division of the rat prefrontal cortex exhibit sparse immunoreactivity for the dopamine transporter. J Neurosci. 1998;18(7):2697–708.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Kaenmaki M, et al. Quantitative role of COMT in dopamine clearance in the prefrontal cortex of freely moving mice. J Neurochem. 2010;114(6):1745–55.

    CAS  PubMed  Google Scholar 

  122. de Frias CM, et al. Catechol O-methyltransferase Val158Met polymorphism is associated with cognitive performance in nondemented adults. J Cogn Neurosci. 2005;17(7):1018–25.

    PubMed  Google Scholar 

  123. Hughes TF, Beer JC, Jacobsen E, Ganguli M, Chang CCH, Rosano C. Executive function predicts decline in mobility after a fall: The MYHAT study. Exp Gerontol. 2020;137:110948.

    PubMed  PubMed Central  Google Scholar 

  124. Bassareo V, De Luca MA, Di Chiara G. Differential expression of motivational stimulus properties by dopamine in nucleus accumbens shell versus core and prefrontal cortex. J Neurosci. 2002;22(11):4709–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Bassareo V, De Luca MA, Di Chiara G. Differential impact of pavlovian drug conditioned stimuli on in vivo dopamine transmission in the rat accumbens shell and core and in the prefrontal cortex. Psychopharmacology. 2007;191(3):689–703.

    CAS  PubMed  Google Scholar 

  126. Ellwood IT, Patel T, Wadia V, Lee AT, Liptak AT, Bender KJ, et al. Tonic or phasic stimulation of dopaminergic projections to prefrontal cortex causes mice to maintain or deviate from previously learned behavioral strategies. J Neurosci. 2017;37(35):8315–29.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Lapish CC, Ahn S, Evangelista LM, So K, Seamans JK, Phillips AG. Tolcapone enhances food-evoked dopamine efflux and executive memory processes mediated by the rat prefrontal cortex. Psychopharmacology. 2009;202(1–3):521–30.

    CAS  PubMed  Google Scholar 

  128. Wunderlich K, Smittenaar P, Dolan RJ. Dopamine enhances model-based over model-free choice behavior. Neuron. 2012;75(3):418–24.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Sharp ME, Foerde K, Daw ND, Shohamy D. Dopamine selectively remediates 'model-based' reward learning: a computational approach. Brain. 2016;139(Pt 2):355–64.

    PubMed  Google Scholar 

  130. Doll BB, Bath KG, Daw ND, Frank MJ. Variability in dopamine genes dissociates model-based and model-free reinforcement learning. J Neurosci. 2016;36(4):1211–22.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Laatikainen LM, Sharp T, Harrison PJ, Tunbridge EM. Sexually dimorphic effects of catechol-O-methyltransferase (COMT) inhibition on dopamine metabolism in multiple brain regions. PLoS One. 2013;8(4):e61839.

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Clarke HF, Cardinal RN, Rygula R, Hong YT, Fryer TD, Sawiak SJ, et al. Orbitofrontal dopamine depletion upregulates caudate dopamine and alters behavior via changes in reinforcement sensitivity. J Neurosci. 2014;34(22):7663–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Kellendonk C, Simpson EH, Polan HJ, Malleret G, Vronskaya S, Winiger V, et al. Transient and selective overexpression of dopamine D2 receptors in the striatum causes persistent abnormalities in prefrontal cortex functioning. Neuron. 2006;49(4):603–15.

    CAS  PubMed  Google Scholar 

  134. Bohnen NI, Muller MLTM, Kuwabara H, Cham R, Constantine GM, Studenski SA. Age-associated striatal dopaminergic denervation and falls in community-dwelling subjects. J Rehabil Res Dev. 2009;46(8):1045–52.

    PubMed  PubMed Central  Google Scholar 

  135. Cham R, Perera S, Studenski SA, Bohnen NI. Striatal dopamine denervation and sensory integration for balance in middle-aged and older adults. Gait Posture. 2007;26(4):516–25.

    PubMed  Google Scholar 

  136. Cham R, et al. Age-related striatal dopaminergic denervation and severity of a slip perturbation. J Gerontol A Biol Sci Med Sci. 2011;66(9):980–5.

    PubMed  Google Scholar 

  137. Cham R, Studenski SA, Perera S, Bohnen NI. Striatal dopaminergic denervation and gait in healthy adults. Exp Brain Res. 2008;185(3):391–8.

    CAS  PubMed  Google Scholar 

  138. Volkow ND, Gur RC, Wang GJ, Fowler JS, Moberg PJ, Ding YS, et al. Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am J Psychiatry. 1998;155(3):344–9.

    CAS  PubMed  Google Scholar 

  139. Sedaghat-Nejad E, Herzfeld DJ, Shadmehr R. Reward prediction error modulates saccade vigor. J Neurosci. 2019;39(25):5010–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Harris CM, Wolpert DM. Signal-dependent noise determines motor planning. Nature. 1998;394(6695):780–4.

    CAS  PubMed  Google Scholar 

  141. Treadway MT, Buckholtz JW, Cowan RL, Woodward ND, Li R, Ansari MS, et al. Dopaminergic mechanisms of individual differences in human effort-based decision-making. J Neurosci. 2012;32(18):6170–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Irving EL, Steinbach MJ, Lillakas L, Babu RJ, Hutchings N. Horizontal saccade dynamics across the human life span. Invest Ophthalmol Vis Sci. 2006;47(6):2478–84.

    PubMed  Google Scholar 

  143. Treadway MT, Buckholtz JW, Schwartzman AN, Lambert WE, Zald DH. Worth the 'EEfRT'? The effort expenditure for rewards task as an objective measure of motivation and anhedonia. PLoS One. 2009;4(8):e6598.

    PubMed  PubMed Central  Google Scholar 

  144. Ewers M, Teipel SJ, Dietrich O, Schönberg SO, Jessen F, Heun R, et al. Multicenter assessment of reliability of cranial MRI. Neurobiol Aging. 2006;27(8):1051–9.

    CAS  PubMed  Google Scholar 

  145. McGonigle DJ, Howseman AM, Athwal BS, Friston KJ, Frackowiak RSJ, Holmes AP. Variability in fMRI: an examination of intersession differences. Neuroimage. 2000;11(6 Pt 1):708–34.

    CAS  PubMed  Google Scholar 

  146. Zheng JJ, et al. Impact of white matter lesions on physical functioning and fall risk in older people: a systematic review. Stroke. 2011;42(7):2086–90.

    PubMed  Google Scholar 

  147. Daselaar SM, Iyengar V, Davis SW, Eklund K, Hayes SM, Cabeza RE. Less wiring, more firing: low-performing older adults compensate for impaired white matter with greater neural activity. Cereb Cortex. 2015;25(4):983–90.

    PubMed  Google Scholar 

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Acknowledgments

We thank the Genomics Shared Resource at the Ohio State University Comprehensive Cancer Center, Columbus, OH, for conducting the COMT genomics analyses.

Funding

This work was supported in part by grants from the National Institutes of Health (R01AG044424 to BC Clark and P30CA16058 to the Ohio State University’s Comprehensive Cancer Center).

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Author notes

  1. David W. Russ

    Present address: School of Physical Therapy & Rehabilitation Sciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA

Authors and Affiliations

  1. Ohio Musculoskeletal and Neurological Institute (OMNI), Ohio University, 250 Irvine Hall, Athens, OH, 45701, USA

    Simon Moskowitz, David W. Russ, Leatha A. Clark, Nathan P. Wages, Dustin R. Grooms, Julie Suhr, Janet E. Simon, Cody R. Criss & Brian C. Clark

  2. School of Rehabilitation and Communication Sciences, Ohio University, Athens, OH, USA

    David W. Russ

  3. Department of Biomedical Sciences at Ohio University, Athens, OH, USA

    Leatha A. Clark, Nathan P. Wages & Brian C. Clark

  4. Department of Family Medicine at Ohio University, Athens, OH, USA

    Leatha A. Clark

  5. School of Applied Health and Wellness, Ohio University, Athens, OH, USA

    Dustin R. Grooms & Janet E. Simon

  6. Center for Cognitive Aging and Memory, Department of Clinical and Health Psychology, University of Florida, Gainesville, FL, USA

    Adam J. Woods & Andrew O’Shea

  7. Department of Psychology, Ohio University, Athens, OH, USA

    Julie Suhr

  8. Genomics Shared Resource-Comprehensive Cancer Center, The Ohio State University, Athens, OH, USA

    Paolo Fadda

  9. Division of Geriatric Medicine at Ohio University, Athens, OH, USA

    Brian C. Clark

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Correspondence to Brian C. Clark.

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Moskowitz, S., Russ, D.W., Clark, L.A. et al. Is impaired dopaminergic function associated with mobility capacity in older adults?. GeroScience 43, 1383–1404 (2021). https://doi.org/10.1007/s11357-020-00303-z

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