Advertisement

Behavior Model for Assessing Decline in Executive Function During Aging and Neurodegenerative Diseases

  • Brittney Yegla
  • Thomas C. Foster
  • Ashok KumarEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 2011)

Abstract

Executive dysfunction is a characteristic of several psychiatric and neurodegenerative diseases. Interestingly, executive function, which is mediated by the prefrontal cortex (PFC), commonly declines during aging. The attentional set-shifting task (AST) is commonly and extensively used to assess executive function in rodents, primates, and humans. When properly employed, this task can behaviorally assess attention, response inhibition, and cognitive flexibility. The following section uses research on age-related decline in executive function to demonstrate the methods employed and highlight areas that can confound a study if not employed properly.

Key words

Executive function Attention Cognitive flexibility Prefrontal cortex Attentional set-shifting task Aging Neurodegenerative diseases 

Notes

Acknowledgments

Supported by National Institute of Aging grants R37AG036800, R01049711, R01052258, and R01037984 and the Evelyn F. McKnight Brain Research Foundation.

References

  1. 1.
    Downes JJ, Roberts AC, Sahakian BJ, Evenden JL, Morris RG, Robbins TW (1989) Impaired extra-dimensional shift performance in medicated and unmedicated Parkinson’s disease: evidence for a specific attentional dysfunction. Neuropsychologia 27:1329–1343CrossRefGoogle Scholar
  2. 2.
    Owen AM, Roberts AC, Polkey CE, Sahakian BJ, Robbins TW (1991) Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia 29:993–1006CrossRefGoogle Scholar
  3. 3.
    Roberts AC, De Salvia MA, Wilkinson LS, Collins P, Muir JL, Everitt BJ, Robbins TW (1994) 6-Hydroxydopamine lesions of the prefrontal cortex in monkeys enhance performance on an analog of the Wisconsin Card Sort Test: possible interactions with subcortical dopamine. J Neurosci 14:2531–2544CrossRefGoogle Scholar
  4. 4.
    Dias R, Robbins TW, Roberts AC (1996) Primate analogue of the Wisconsin Card Sorting Test: effects of excitotoxic lesions of the prefrontal cortex in the marmoset. Behav Neurosci 110:872–886CrossRefGoogle Scholar
  5. 5.
    Barense MD, Fox MT, Baxter MG (2002) Aged rats are impaired on an attentional set-shifting task sensitive to medial frontal cortex damage in young rats. Learn Mem 9:191–201CrossRefGoogle Scholar
  6. 6.
    Floresco SB, Block AE, Tse MT (2008) Inactivation of the medial prefrontal cortex of the rat impairs strategy set-shifting, but not reversal learning, using a novel, automated procedure. Behav Brain Res 190:85–96CrossRefGoogle Scholar
  7. 7.
    Brown VJ, Tait DS (2016) Attentional set-shifting across species. Curr Top Behav Neurosci 28:363–395CrossRefGoogle Scholar
  8. 8.
    McAlonan K, Brown VJ (2003) Orbital prefrontal cortex mediates reversal learning and not attentional set shifting in the rat. Behav Brain Res 146:97–103CrossRefGoogle Scholar
  9. 9.
    Block AE, Dhanji H, Thompson-Tardif SF, Floresco SB (2007) Thalamic-prefrontal cortical-ventral striatal circuitry mediates dissociable components of strategy set shifting. Cereb Cortex 17:1625–1636CrossRefGoogle Scholar
  10. 10.
    Ghods-Sharifi S, Haluk DM, Floresco SB (2008) Differential effects of inactivation of the orbitofrontal cortex on strategy set-shifting and reversal learning. Neurobiol Learn Mem 89:567–573CrossRefGoogle Scholar
  11. 11.
    Newman LA, McGaughy J (2011) Attentional effects of lesions to the anterior cingulate cortex: how prior reinforcement influences distractibility. Behav Neurosci 125:360–371CrossRefGoogle Scholar
  12. 12.
    Chase EA, Tait DS, Brown VJ (2012) Lesions of the orbital prefrontal cortex impair the formation of attentional set in rats. Eur J Neurosci 36:2368–2375CrossRefGoogle Scholar
  13. 13.
    Lindgren HS, Wickens R, Tait DS, Brown VJ, Dunnett SB (2013) Lesions of the dorsomedial striatum impair formation of attentional set in rats. Neuropharmacology 71:148–153CrossRefGoogle Scholar
  14. 14.
    Wright NF, Vann SD, Aggleton JP, Nelson AJ (2015) A critical role for the anterior thalamus in directing attention to task-relevant stimuli. J Neurosci 35:5480–5488CrossRefGoogle Scholar
  15. 15.
    Tait DS, Phillips JM, Blackwell AD, Brown VJ (2017) Effects of lesions of the subthalamic nucleus/zona incerta area and dorsomedial striatum on attentional set-shifting in the rat. Neuroscience 345:287–296CrossRefGoogle Scholar
  16. 16.
    Egerton A, Reid L, McKerchar CE, Morris BJ, Pratt JA (2005) Impairment in perceptual attentional set-shifting following PCP administration: a rodent model of set-shifting deficits in schizophrenia. Psychopharmacology 179:77–84CrossRefGoogle Scholar
  17. 17.
    Floresco SB, Magyar O, Ghods-Sharifi S, Vexelman C, Tse MT (2006) Multiple dopamine receptor subtypes in the medial prefrontal cortex of the rat regulate set-shifting. Neuropsychopharmacology 31:297–309CrossRefGoogle Scholar
  18. 18.
    Tait DS, Brown VJ, Farovik A, Theobald DE, Dalley JW, Robbins TW (2007) Lesions of the dorsal noradrenergic bundle impair attentional set-shifting in the rat. Eur J Neurosci 25:3719–3724CrossRefGoogle Scholar
  19. 19.
    McGaughy J, Ross RS, Eichenbaum H (2008) Noradrenergic, but not cholinergic, deafferentation of prefrontal cortex impairs attentional set-shifting. Neuroscience 153:63–71CrossRefGoogle Scholar
  20. 20.
    Tait DS, Brown VJ (2008) Lesions of the basal forebrain impair reversal learning but not shifting of attentional set in rats. Behav Brain Res 187:100–108CrossRefGoogle Scholar
  21. 21.
    Parikh V, Naughton SX, Yegla B, Guzman DM (2016) Impact of partial dopamine depletion on cognitive flexibility in BDNF heterozygous mice. Psychopharmacology 233:1361–1375CrossRefGoogle Scholar
  22. 22.
    Beas BS, McQuail JA, Ban Uelos C, Setlow B, Bizon JL (2017) Prefrontal cortical GABAergic signaling and impaired behavioral flexibility in aged F344 rats. Neuroscience 345:274–286CrossRefGoogle Scholar
  23. 23.
    Babcock RL, Salthouse TA (1990) Effects of increased processing demands on age differences in working memory. Psychol Aging 5:421–428CrossRefGoogle Scholar
  24. 24.
    Robbins TW, James M, Owen AM, Sahakian BJ, Lawrence AD, McInnes L, Rabbitt PM (1998) A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: implications for theories of executive functioning and cognitive aging. Cambridge Neuropsychological Test Automated Battery. J Int Neuropsychol Soc 4:474–490CrossRefGoogle Scholar
  25. 25.
    Fortenbaugh FC, DeGutis J, Germine L, Wilmer JB, Grosso M, Russo K, Esterman M (2015) Sustained attention across the life span in a sample of 10,000: dissociating ability and strategy. Psychol Sci 26:1497–1510CrossRefGoogle Scholar
  26. 26.
    Rhodes MG (2004) Age-related differences in performance on the Wisconsin card sorting test: a meta-analytic review. Psychol Aging 19:482–494CrossRefGoogle Scholar
  27. 27.
    Picq JL (2007) Aging affects executive functions and memory in mouse lemur primates. Exp Gerontol 42:223–232CrossRefGoogle Scholar
  28. 28.
    Wallace J, Marston HM, McQuade R, Gartside SE (2014) Evidence that the attentional set shifting test in rats can be applied in repeated testing paradigms. J Psychopharmacol 28:691–696CrossRefGoogle Scholar
  29. 29.
    Birrell JM, Brown VJ (2000) Medial frontal cortex mediates perceptual attentional set shifting in the rat. J Neurosci 20:4320–4324CrossRefGoogle Scholar
  30. 30.
    Ando S, Ohashi Y (1991) Longitudinal study on age-related changes of working and reference memory in the rat. Neurosci Lett 128:17–20CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Brittney Yegla
    • 1
  • Thomas C. Foster
    • 1
  • Ashok Kumar
    • 1
    • 2
    Email author
  1. 1.McKnight Brain InstituteUniversity of FloridaGainesvilleUSA
  2. 2.Department of Neuroscience, McKnight Brain InstituteUniversity of FloridaGainesvilleUSA

Personalised recommendations