Abstract
Little is known about the effects of exercise training (ET) on lexical characteristics during fluency task and its association with cerebellum functional connectivity. The purposes of this study were (1) to investigate whether ET alters response patterns during phonemic and semantic fluency tasks and (2) to assess the association between ET-related changes in cerebellum functional connectivity (FC) and lexical characteristics during fluency tasks. Thirty-five older adults (78.0 ± 7.1 years; 17 mild cognitive impairment (MCI) and 18 healthy cognition (HC)) underwent a 12-week treadmill ET. Before and after ET, cardiorespiratory fitness tests, phonemic and semantic fluency tests, and resting-state fMRI scans were administered. We utilized a seed-based correlation analysis to measure cerebellum FC and linear regression to assess the association of residualized ET-induced Δcerebellum FC with Δtask performance. Improved mean switches and frequency during the phonemic fluency task were observed following ET in all participants. There were significant associations between ET-induced increases in cerebellum FC and greater phonemic fluency task log frequency, increases in mean switches, and a reduction in the number of syllables in HC. Lastly, there was a significant interaction between group and cerebellar connectivity on phonemic fluency mean log frequency and number of syllables. A 12-week walking ET is related to enhanced phonemic fluency lexical characteristics in older adults with MCI and HC. The association between ET-induced increases in cerebellum FC and enhanced response patterns after ET suggests that the cerebellum may play an important role in ET-related improvement in phonemic fluency performance in cognitively healthy older adults.
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References
Clark LJ, Gatz M, Zheng L, Chen Y-L, McCleary C, Mack WJ. Longitudinal verbal fluency in normal aging, preclinical, and prevalent Alzheimer’s disease. Am J Alzheimers Dis Dementias®. 2009;24(6):461–8.
Kempler D, Zelinski EM. Language in dementia and normal aging. In: Huppert F, Brayne C, O’Connor D, eds. Dementia and Normal Aging. Cambridge: Cambridge University Press; 1994:331–65.
Burke DM, Shafto MA. Aging and language production. Curr Dir Psychol Sci. 2004;13(1):21–4.
Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, et al. Mild cognitive impairment. Lancet. 2006;367(9518):1262–70.
Lezak MD, Howieson DB, Loring DW, Fischer JS. Neuropsychological assessment. USA: Oxford University Press; 2004.
Fisk JE, Sharp CA. Age-related impairment in executive functioning: updating, inhibition, shifting, and access. J Clin Exp Neuropsychol. 2004;26(7):874–90.
Troyer AK, Moscovitch M, Winocur G, Alexander MP, Stuss DON. Clustering and switching on verbal fluency: the effects of focal frontal-and temporal-lobe lesions. Neuropsychologia. 1998;36(6):499–504.
Henry JD, Crawford JR, Phillips LH. Verbal fluency performance in dementia of the Alzheimer’s type: a meta-analysis. Neuropsychologia. 2004;42(9):1212–22.
Abwender DA, Swan JG, Bowerman JT, Connolly SW. Qualitative analysis of verbal fluency output: review and comparison of several scoring methods. Assessment. 2001;8(3):323–38.
Bélanger S, Belleville S. Semantic inhibition impairment in mild cognitive impairment: a distinctive feature of upcoming cognitive decline? Neuropsychology. 2009;23(5):592–606.
Duong A, Whitehead V, Hanratty K, Chertkow H. The nature of lexico-semantic processing deficits in mild cognitive impairment. Neuropsychologia. 2006;44(10):1928–35.
Brickman AM, Paul RH, Cohen RA, Williams LM, MacGregor KL, Jefferson AL, et al. Category and letter verbal fluency across the adult lifespan: relationship to EEG theta power. Arch Clin Neuropsychol. 2005;20(5):561–73.
Rodríguez-Aranda C, Martinussen M. Age-related differences in performance of phonemic verbal fluency measured by Controlled Oral Word Association Task (COWAT): a meta-analytic study. Dev Neuropsychol. 2006;30(2):697–717.
Mirandez RM, Aprahamian I, Talib LL, Forlenza OV, Radanovic M. Multiple category verbal fluency in mild cognitive impairment and correlation with CSF biomarkers for Alzheimer’s disease. Int Psychogeriatr. 2017;29(6):949–58.
Brown BM, Peiffer JJ, Sohrabi HR, Mondal A, Gupta VB, Rainey-Smith SR, et al. Intense physical activity is associated with cognitive performance in the elderly. Transl Psychiatry. 2012;2(11):e191–e191.
Nocera JR, McGregor KM, Hass CJ, Crosson B. Spin exercise improves semantic fluency in previously sedentary older adults. J Aging Phys Act. 2015;23(1):90–4.
Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, et al. Effects of aerobic exercise on mild cognitive impairment: a controlled trial. Arch Neurol. 2010;67(1):71–9.
Alfini AJ, Weiss LR, Nielson KA, Verber MD, Smith JC. Resting cerebral blood flow after exercise training in mild cognitive impairment. J Alzheimers Dis. 2019;67(2):671–84.
Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005;102(27):9673–8.
Damoiseaux JS, Rombouts SA, Barkhof F, Scheltens P, Stam CJ, Smith SM, et al. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci. 2006;103(37):13848–53.
Voss MW, Erickson KI, Prakash RS, Chaddock L, Malkowski E, Alves H, et al. Functional connectivity: a source of variance in the association between cardiorespiratory fitness and cognition? Neuropsychologia. 2010;48(5):1394–406.
Voss MW, Prakash RS, Erickson KI, Basak C, Chaddock L, Kim JS, et al. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults. Front Aging Neurosci. 2010;2:32.
Buckner RL, Krienen FM, Castellanos A, Diaz JC, Yeo BT. The organization of the human cerebellum estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106(5):2322–45.
Krienen FM, Buckner RL. Segregated fronto-cerebellar circuits revealed by intrinsic functional connectivity. Cereb Cortex. 2009;19(10):2485–97.
Stoodley CJ. The cerebellum and cognition: evidence from functional imaging studies. Cerebellum. 2012;11(2):352–65.
Buckner RL. The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging. Neuron. 2013;80(3):807–15.
Keren-Happuch E, Chen S-HA, Ho M-HR, Desmond JE. A meta-analysis of cerebellar contributions to higher cognition from PET and fMRI studies. Hum Brain Mapp. 2014;35(2):593.
Richter S, Gerwig M, Aslan B, Wilhelm H, Schoch B, Dimitrova A, et al. Cognitive functions in patients with MR-defined chronic focal cerebellar lesions. J Neurol. 2007;254(9):1193–203.
Rodríguez-Aranda C, Johnsen SH, Eldevik P, Sparr S, Wikran GC, Herder M, et al. Neuroanatomical correlates of verbal fluency in early Alzheimer’s disease and normal aging. Brain Lang. 2016;155:24–35.
Weiss EM, Siedentopf C, Hofer A, Deisenhammer EA, Hoptman MJ, Kremser C, et al. Brain activation pattern during a verbal fluency test in healthy male and female volunteers: a functional magnetic resonance imaging study. Neurosci Lett. 2003;352(3):191–4.
Miró-Padilla A, Bueichekú E, Ventura-Campos N, Palomar-García M-Á, Ávila C. Functional connectivity in resting state as a phonemic fluency ability measure. Neuropsychologia. 2017;97:98–103.
Angelucci F, De Bartolo P, Gelfo F, Foti F, Cutuli D, Bossù P, et al. Increased concentrations of nerve growth factor and brain-derived neurotrophic factor in the rat cerebellum after exposure to environmental enrichment. Cerebellum. 2009;8(4):499–506.
Vazquez-Sanroman D, Sanchis-Segura C, Toledo R, Hernández ME, Manzo J, Miquel M. The effects of enriched environment on BDNF expression in the mouse cerebellum depending on the length of exposure. Behav Brain Res. 2013;243:118–28.
Ben-Soussan TD, Berkovich-Ohana A, Piervincenzi C, Glicksohn J, Carducci F. Embodied cognitive flexibility and neuroplasticity following Quadrato Motor Training. Front Psychol. 2015;6:1021.
Smith JC, Nielson KA, Antuono P, Lyons JA, Hanson RJ, Butts AM, et al. Semantic memory functional MRI and cognitive function after exercise intervention in mild cognitive impairment. J Alzheimers Dis. 2013;37(1):197–215.
Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. 1971;9(1):97–113.
Yesavage JA. Geriatric Depression Scale. Psychopharmacol Bull. 1988;24(4):709–11.
Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist. 1969;9(3_Part_1):179–86.
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):270–9.
Ruff RM, Light RH, Parker SB, Levin HS. Benton controlled oral word association test: reliability and updated norms. Arch Clin Neuropsychol. 1996;11(4):329–38.
Tombaugh TN, Kozak J, Rees L. Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming. Arch Clin Neuropsychol. 1999;14(2):167–77.
Brysbaert M, New B. Moving beyond Kučera and Francis: a critical evaluation of current word frequency norms and the introduction of a new and improved word frequency measure for American English. Behav Res Methods. 2009;41(4):977–90.
Bird H, Franklin S, Howard D. Age of acquisition and imageability ratings for a large set of words, including verbs and function words. Behav Res Methods Instrum Comput. 2001;33(1):73–9.
Borg G. Psychophysical scaling with applications in physical work and the perception of exertion. Scandinavian journal of work, environment & health. 1990;1:55–8.
Fischl B. FreeSurfer. Neuroimage. 2012;62(2):774–781.
Cox RW. AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res. 1996 Jun 1;29(3):162–73.
Beall EB, Lowe MJ. SimPACE: generating simulated motion corrupted BOLD data with synthetic-navigated acquisition for the development and evaluation of SLOMOCO: a new, highly effective slicewise motion correction. Neuroimage. 2014;101:21–34.
Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage. 2009;44(2):489–501.
Yarkoni T, Poldrack RA, Nichols TE, Van Essen DC, Wager TD. Large-scale automated synthesis of human functional neuroimaging data. Nat Methods. 2011;8(8):665–70.
Sutter C, Zöllig J, Martin M. Plasticity of verbal fluency in older adults: a 90-minute telephone-based intervention. Gerontology. 2013;59(1):53–63.
Desikan RS, Ségonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006;31(3):968–80.
Alfini AJ, Weiss LR, Leitner BP, Smith TJ, Hagberg JM, Smith JC. Hippocampal and cerebral blood flow after exercise cessation in master athletes. Front Aging Neurosci. 2016;8:184.
Juhasz BJ, Chambers D, Shesler LW, Haber A, Kurtz MM. Evaluating lexical characteristics of verbal fluency output in schizophrenia. Psychiatry Res. 2012;200(2–3):177–83.
Kramer AF, Hahn S, Cohen NJ, Banich MT, McAuley E, Harrison CR, et al. Ageing, fitness and neurocognitive function. Nature. 1999;400(6743):418–9.
Leggio MG, Silveri MC, Petrosini L, Molinari M. Phonological grouping is specifically affected in cerebellar patients: a verbal fluency study. J Neurol Neurosurg Psychiatry. 2000;69(1):102–6.
Molinari M, Chiricozzi FR, Clausi S, Tedesco AM, De Lisa M, Leggio MG. Cerebellum and detection of sequences, from perception to cognition. Cerebellum. 2008;7(4):611–5.
Ramnani N. Frontal lobe and posterior parietal contributions to the cortico-cerebellar system. Cerebellum. 2012;11(2):366–83.
Alalade E, Denny K, Potter G, Steffens D, Wang L. Altered cerebellar-cerebral functional connectivity in geriatric depression. PloS One. 2011;6(5):e20035.
Schmahmann JD. From movement to thought: anatomic substrates of the cerebellar contribution to cognitive processing. Hum Brain Mapp. 1996;4(3):174–98.
Leiner HC, Leiner AL, Dow RS. The human cerebro-cerebellar system: its computing, cognitive, and language skills. Behav Brain Res. 1991;44(2):113–28.
Menon V. Large-scale brain networks in cognition: emerging principles. Anal Funct Large-Scale Brain Netw. 2010;14:43–54.
Buckner RL, Andrews-Hanna JR, Schacter DL. The brain’s default network: anatomy, function, and relevance to disease. 2008
Gourovitch ML, Kirkby BS, Goldberg TE, Weinberger DR, Gold JM, Esposito G, et al. A comparison of rCBF patterns during letter and semantic fluency. Neuropsychology. 2000;14(3):353–60.
Yin S, Zhu X, He R, Li R, Li J. Spontaneous activity in the precuneus predicts individual differences in verbal fluency in cognitively normal elderly. Neuropsychology. 2015;29(6):961–70.
Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R, McAuley E, et al. Aerobic exercise training increases brain volume in aging humans. J Gerontol A Biol Sci Med Sci. 2006;61(11):1166–70.
Won J, Alfini AJ, Weiss LR, Callow DD, Smith JC. Brain activation during executive control after acute exercise in older adults. Int J Psychophysiol. 2019;146:240–8.
Luo L, Luk G, Bialystok E. Effect of language proficiency and executive control on verbal fluency performance in bilinguals. Cognition. 2010;114(1):29–41.
Chirles TJ, Reiter K, Weiss LR, Alfini AJ, Nielson KA, Smith JC. Exercise training and functional connectivity changes in mild cognitive impairment and healthy elders. J Alzheimers Dis. 2017;57(3):845–56.
Reiter K, Nielson KA, Smith TJ, Weiss LR, Alfini AJ, Smith JC. Improved cardiorespiratory fitness is associated with increased cortical thickness in mild cognitive impairment. J Int Neuropsychol Soc. 2015;21(10):757–67.
Qi Z, An Y, Zhang M, Li H-J, Lu J. Altered cerebro-cerebellar limbic network in AD spectrum: a resting-state fMRI study. Front Neural Circuits. 2019;13:72.
Nocera J, Crosson B, Mammino K, McGregor KM. Changes in cortical activation patterns in language areas following an aerobic exercise intervention in older adults. Neural Plast. 2017;2017:1–9.
Zlatar ZZ, Towler S, McGregor KM, Dzierzewski JM, Bauer A, Phan S, et al. Functional language networks in sedentary and physically active older adults. J Int Neuropsychol Soc. 2013;19(6):625–34.
Reuter-Lorenz PA, Park DC. How does it STAC up? Revisiting the scaffolding theory of aging and cognition. Neuropsychol Rev. 2014;24(3):355–70.
Hyodo K, Dan I, Suwabe K, Kyutoku Y, Yamada Y, Akahori M, et al. Acute moderate exercise enhances compensatory brain activation in older adults. Neurobiol Aging. 2012;33(11):2621–32.
Meeusen R, Smolders I, Sarre S, De Meirleir K, Keizer H, Serneels M, et al. Endurance training effects on neurotransmitter release in rat striatum: an in vivo microdialysis study. Acta Physiol Scand. 1997;159(4):335–41.
Isaacs KR, Anderson BJ, Alcantara AA, Black JE, Greenough WT. Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning. J Cereb Blood Flow Metab. 1992;12(1):110–9.
Carro E, Nuñez A, Busiguina S, Torres-Aleman I. Circulating insulin-like growth factor I mediates effects of exercise on the brain. J Neurosci. 2000;20(8):2926–33.
Won J, Alfini AJ, Weiss LR, Michelson CS, Callow DD, Ranadive SM, et al. Semantic memory activation after acute exercise in healthy older adults. J Int Neuropsychol Soc. 2019;25(6):557–68.
Won J, Alfini AJ, Weiss LR, Hagberg JM, Smith JC. Greater semantic memory activation after exercise training cessation in older endurance-trained athletes. J Aging Phys Act. 2020;1(aop):1–9.
Woo C-W, Krishnan A, Wager TD. Cluster-extent based thresholding in fMRI analyses: pitfalls and recommendations. Neuroimage. 2014;91:412–9.
Devanand DP, Liu X, Brown PJ, Huey ED, Stern Y, Pelton GH. A two-study comparison of clinical and MRI markers of transition from mild cognitive impairment to Alzheimer’s disease. Int J Alzheimers Dis. 2012;2012:1–8.
Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci. 2011;108(7):3017–22.
Cole DM, Smith SM, Beckmann CF. Advances and pitfalls in the analysis and interpretation of resting-state FMRI data. Front Syst Neurosci. 2010;4:8.
Acknowledgments
We thank the participants for their dedication while participating in this study and Drs. Nathan Hantke and Alissa Butts for their assistance with participant assessment. This study was supported by the University of Wisconsin-Milwaukee Graduate School Research Growth Initiative and the National Center for Advancing Translational Sciences, NIH grant numbers 8UL1TR000055 and 8KL2TR000056. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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J.W. and J.C.S. developed the study idea. J.C.S. and K.N. developed overall study protocol and collected data. J.W. processed and analyzed imaging data. A.W., A.A., D.C., and Y.F-S. analyzed phonemic and semantic fluency data. J.W., J.C.S, K.N., and Y.F-S. interpreted the data. J.W. and J.C.S. collectively developed the analytic strategy. J.W. drafted the paper and J.W., J.C.S, K.N., Y.F-S., A.W., and D.C. edited the paper. J.W. created the figures. All authors reviewed, revised, and approved the final manuscript.
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Won, J., Faroqi-Shah, Y., Callow, D.D. et al. Association Between Greater Cerebellar Network Connectivity and Improved Phonemic Fluency Performance After Exercise Training in Older Adults. Cerebellum 20, 542–555 (2021). https://doi.org/10.1007/s12311-020-01218-3
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DOI: https://doi.org/10.1007/s12311-020-01218-3