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  • Journal of the International Neuropsychological Society, Volume 16, Issue 4
  • July 2010, pp. 640-650

Gray matter correlates of set-shifting among neurodegenerative disease, mild cognitive impairment, and healthy older adults

  • DOI:
  • Published online: 01 April 2010

There is increasing recognition that set-shifting, a form of cognitive control, is mediated by different neural structures. However, these regions have not yet been carefully identified as many studies do not account for the influence of component processes (e.g., motor speed). We investigated gray matter correlates of set-shifting while controlling for component processes. Using the Design Fluency (DF), Trail Making Test (TMT), and Color Word Interference (CWI) subtests from the Delis-Kaplan Executive Function System (D-KEFS), we investigated the correlation between set-shifting performance and gray matter volume in 160 subjects with neurodegenerative disease, mild cognitive impairment, and healthy older adults using voxel-based morphometry. All three set-shifting tasks correlated with multiple, widespread gray matter regions. After controlling for the component processes, set-shifting performance correlated with focal regions in prefrontal and posterior parietal cortices. We also identified bilateral prefrontal cortex and the right posterior parietal lobe as common sites for set-shifting across the three tasks. There was a high degree of multicollinearity between the set-shifting conditions and the component processes of TMT and CWI, suggesting DF may better isolate set-shifting regions. Overall, these findings highlight the neuroanatomical correlates of set-shifting and the importance of controlling for component processes when investigating complex cognitive tasks. (JINS, 2010, 16, 640–650.)

Corresponding author
*Correspondence and reprint requests to: Judy Pa, UCSF Mission Bay, Genentech Hall, Room N474, 600 16th Street, San Francisco, CA 94158. E-mail:
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This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

S.W. Anderson , H. Damasio , R.D. Jones , & D. Tranel (1991). Wisconsin Card Sorting Test performance as a measure of frontal lobe damage. Journal of Clinical and Experimental Neuropsychology, 13, 909922.

A.R. Aron , S. Monsell , B.J. Sahakian , & T.W. Robbins (2004). A componential analysis of task-switching deficits associated with lesions of left and right frontal cortex. Brain, 127(Pt 7), 15611573.

A.R. Aron , L. Watkins , B.J. Sahakian , S. Monsell , R.A. Barker , & T.W. Robbins (2003). Task-set switching deficits in early-stage Huntington’s disease: Implications for basal ganglia function. Journal of Cognitive Neuroscience, 15, 629642.

T. Asari , S. Konishi , K. Jimura , & Y. Miyashita (2005). Multiple components of lateral posterior parietal activation associated with cognitive set shifting. Neuroimage, 26, 694702.

J. Ashburner (2007). A fast diffeomorphic image registration algorithm. Neuroimage, 38, 95113.

A.D. Barber , & C.S. Carter (2005). Cognitive control involved in overcoming prepotent response tendencies and switching between tasks. Cerebral Cortex, 15, 899912.

M. Brass , M. Ullsperger , T.R. Knoesche , D.Y. von Cramon , & N.A. Phillips (2005). Who comes first? The role of the prefrontal and parietal cortex in cognitive control. Journal of Cognitive Neuroscience, 17, 13671375.

B.R. Brooks (1994). El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. Journal of the Neurological Sciences, 160, S25S29.

R. Cools , R.A. Barker , B.J. Sahakian , & T.W. Robbins (2001). Mechanisms of cognitive set flexibility in Parkinson’s disease. Brain, 124(Pt 12), 25032512.

R. Corcoran , & D. Upton (1993). A role for the hippocampus in card sorting? Cortex, 29, 293304.

E.A. Crone , C. Wendelken , S.E. Donohue , & S.A. Bunge (2006). Neural evidence for dissociable components of task-switching. Cerebral Cortex, 16, 475486.

J.L. Cummings (1997). The neuropsychiatric inventory: Assessing psychopathology in dementia patients. Neurology, 48(Suppl. 6), S10S16.

J. Derrfuss , M. Brass , & D.Y. von Cramon (2004). Cognitive control in the posterior frontolateral cortex: Evidence from common activations in task coordination, interference control, and working memory. Neuroimage, 23, 604612.

P.J. Eslinger , & L.M. Grattan (1993). Frontal lobe and frontal-striatal substrates for different forms of human cognitive flexibility. Neuropsychologia, 31, 1728.

M.F. Folstein , S.E. Folstein , & P.R. McHugh (1975). “Mini-mental state”. A practical method for grading the mental state of patients for the clinician. Journal of Psychiatric Research, 12, 189198.

S. Garbutt , A. Matlin , J. Hellmuth , A.K. Schenk , J.K. Johnson , H. Rosen , . (2008). Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer’s disease. Brain, 131, 12681281.

E.D. Huey , E.N. Goveia , S. Paviol , M. Pardini , F. Krueger , G. Zamboni , . (2009). Executive dysfunction in frontotemporal dementia and corticobasal syndrome. Neurology, 72, 453459.

S. Jazbec , C. Pantelis , T. Robbins , T. Weickert , D.R. Weinberger , & T.E. Goldberg (2007). Intra-dimensional/extra-dimensional set-shifting performance in schizophrenia: Impact of distractors. Schizophrenia Research, 89, 339349.

A. Kertesz , & G. Munoz (2004). Relationship between frontotemporal dementia and corticobasal degeneration/progressive supranuclear palsy. Dementia and Geriatric Cognitive Disorders, 17, 282286.

S. Konishi , T. Hayashi , I. Uchida , H. Kikyo , E. Takahashi , & Y. Miyashita (2002). Hemispheric asymmetry in human lateral prefrontal cortex during cognitive set shifting. Proceedings of the National Academy of Sciences of the United States of America, 99, 78037808.

J.H. Kramer , J. Jurik , S.J. Sha , K.P. Rankin , H.J. Rosen , J.K. Johnson , . (2003). Distinctive neuropsychological patterns in frontotemporal dementia, semantic dementia, and Alzheimer disease. Cognitive and Behavioral Neurology, 16, 211218.

A.D. Lawrence , J.R. Hodges , A.E. Rosser , A. Kershaw , C. ffrench-Constant , D.C. Rubinsztein , . (1998). Evidence for specific cognitive deficits in preclinical Huntington’s disease. Brain, 121(Pt 7), 13291341.

C.H. Lie , K. Specht , J.C. Marshall , & G.R. Fink (2006). Using fMRI to decompose the neural processes underlying the Wisconsin Card Sorting Test. Neuroimage, 30, 10381049.

G.A. Marshall , R. Hendrickson , D.I. Kaufer , L.S. Ivanco , & N.I. Bohnen (2006). Cognitive correlates of brain MRI subcortical signal hyperintensities in non-demented elderly. International Journal of Geriatric Psychiatry, 21, 3235.

U. Mayr , J. Diedrichsen , R. Ivry , & S.W. Keele (2006). Dissociating task-set selection from task-set inhibition in the prefrontal cortex. Journal of Cognitive Neuroscience, 18, 1421.

C.R. McDonald , D.C. Delis , M.A. Norman , S.R. Wetter , E.S. Tecoma , & V.J. Iragui (2005). Response inhibition and set shifting in patients with frontal lobe epilepsy or temporal lobe epilepsy. Epilepsy & Behavior, 7, 438446.

I.G. McKeith , D.W. Dickson , J. Lowe , M. Emre , J.T. O’Brien , H. Feldman , . (2005). Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium. Neurology, 65, 18631872.

G. McKhann , D. Drachman , M. Folstein , R. Katzman , D. Price , & E.M. Stadlan (1984). Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology, 34, 939944.

J. Moll , R. de Oliveira-Souza , F.T. Moll , I.E. Bramati , & P.A. Andreiuolo (2002). The cerebral correlates of set-shifting: An fMRI study of the trail making test. Arquivos de Neuro-psiquiatria, 60, 900905.

O. Monchi , M. Petrides , A.P. Strafella , K.J. Worsley , & J. Doyon (2006). Functional role of the basal ganglia in the planning and execution of actions. Annals of Neurology, 59, 257264.

J.C. Morris (1993). The Clinical Dementia Rating (CDR): Current version and scoring rules [see comments]. Neurology, 43, 24122414.

A. Nagano-Saito , M. Leyton , O. Monchi , Y.K. Goldberg , Y. He , & A. Dagher (2008). Dopamine depletion impairs frontostriatal functional connectivity during a set-shifting task. Journal of Neuroscience, 28, 36973706.

D. Neary , J.S. Snowden , L. Gustafson , U. Passant , D. Stuss , S. Black , . (1998). Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria. Neurology, 51, 15461554.

L.M. Newman , M.A. Trivedi , B.B. Bendlin , M.L. Ries , & S.C. Johnson (2007). The relationship between gray matter morphometry and neuropsychological performance in a large sample of cognitively healthy adults. Brain Imaging and Behavior, 1, 310.

A.M. Owen , A.C. Roberts , C.E. Polkey , B.J. Sahakian , & T.W. Robbins (1991). Extra-dimensional versus intra-dimensional set shifting performance following frontal lobe excisions, temporal lobe excisions or amygdalo-hippocampectomy in man. Neuropsychologia, 29, 9931006.

J. Pa , A.L. Boxer , K. Freeman , J. Kramer , B.L. Miller , L.L. Chao , . (2009). Clinical-Neuroimaging Characteristics of Dysexecutive Mild Cognitive Impairment. Annals of Neurology, 65, 414423.

C. Pantelis , F.Z. Barber , T.R. Barnes , H.E. Nelson , A.M. Owen , & T.W. Robbins (1999). Comparison of set-shifting ability in patients with chronic schizophrenia and frontal lobe damage. Schizophrenia Research, 37, 251270.

J.M.S. Pereira , L. Xiong , J. Acosta-Cabronero , G. Pengas , G.B. Williams , & P.J. Nestor (2009). Registration accuracy for VBM studies varies according to region and degenerative disease grouping. Neuroimage, 49, 22052215.

M.E. Perry , C.R. McDonald , D.J. Hagler Jr., L. Gharapetian , J.M. Kuperman , A.K. Koyama , . (2009). White matter tracts associated with set-shifting in healthy aging. Neuropsychologia, 47, 28352842.

S.M. Ravizza , & M.A. Ciranni (2002). Contributions of the prefrontal cortex and basal ganglia to set shifting. Journal of Cognitive Neuroscience, 14, 472483.

C.H. Salmond , J. Ashburner , F. Vargha-Khadem , A. Connelly , D.G. Gadian , & K.J. Friston (2002). Distributional assumptions in voxel-based morphometry. Neuroimage, 17, 10271030.

J.D. Schmahmann , & J.C. Sherman (1998). The cerebellar cognitive affective syndrome. Brain, 121(Pt 4), 561579.

A.B. Smith , E. Taylor , M. Brammer , & K. Rubia (2004). Neural correlates of switching set as measured in fast, event-related functional magnetic resonance imaging. Human Brain Mapping, 21, 247256.

E. Strauss , M. Hunter , & J. Wada (1993). Wisconsin Card Sorting Performance: Effects of age of onset of damage and laterality of dysfunction. Journal of Clinical and Experimental Neuropsychology, 15, 896902.

J. Stroop (1935). Studies of interferences in serial verbal reactions. Journal of Experimental Psychology, 18, 643662.

D.T. Stuss , S.M. Bisschop , M.P. Alexander , B. Levine , D. Katz , & D. Izukawa (2001). The Trail Making Test: A study in focal lesion patients. Psychological Assessment, 13, 230239.

I. Tamura , S. Kikuchi , M. Otsuki , M. Kitagawa , & K. Tashiro (2003). Deficits of working memory during mental calculation in patients with Parkinson’s disease. Journal of the Neurological Sciences, 209, 1923.

T.D. Wager , J. Jonides , & S. Reading (2004). Neuroimaging studies of shifting attention: A meta-analysis. Neuroimage, 22, 16791693.

B. Winblad , K. Palmer , M. Kivipelto , V. Jelic , L. Fratiglioni , L.O. Wahlund , . (2004). Mild cognitive impairment–beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment. Journal of Internal Medicine, 256, 240246.

T.S. Woodward , D.N. Bub , & M.A. Hunter (2002). Task switching deficits associated with Parkinson’s disease reflect depleted attentional resources. Neuropsychologia, 40, 19481955.

J.A. Yesavage , T.L. Brink , T.L. Rolse , O. Lum , V. Huang , M. Adey , . (1983). Development and validity of a geriatric depression scale: A preliminary report. Journal of Psychiatric Research, 17, 3749.

K.K. Zakzanis , R. Mraz , & S.J. Graham (2005). An fMRI study of the Trail Making Test. Neuropsychologia, 43, 18781886.

M.E. Zimmerman , A.M. Brickman , R.H. Paul , S.M. Grieve , D.F. Tate , J. Gunstad , . (2006). The relationship between frontal gray matter volume and cognition varies across the healthy adult lifespan. American Journal of Geriatric Psychiatry, 14, 823833.

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