Skip to main content Accessibility help

Magnetic resonance imaging correlates of set shifting



The purpose of this study was to examine the relationships between lobar volumes and set shifting. We studied 101 subjects, including 36 normal controls, 16 patients with probable Alzheimer's disease, 30 patients with frontotemporal dementia (FTD), and 19 patients with semantic dementia (SD), using a shifting paradigm that carefully controlled for component abilities. Subjects were administered two conditions of the Delis–Kaplan Executive Function System (D-KEFS) Design Fluency Test. In the control condition (DF:Control), examinees generated as many unique designs as possible in 60 s by drawing lines connecting only unfilled dots. In the switching condition (DF:Switch), examinees generated designs by drawing lines alternating between filled and unfilled dots. We used BRAINS2 software to generate volumes of the right and left frontal, temporal, and parietal lobes. Partial correlations and multiple regressions showed that, after controlling for Mini-Mental State Examination and DF:Control, only the right and left frontal lobe volumes significantly correlated with the DF:Switch, most clearly in the FTD and SD groups. Follow-up analyses indicated that frontal contributions to shifting were not related to working memory. Results highlight the importance of carefully controlling for component cognitive processes when studying executive functioning. (JINS, 2007, 13, 386–392.)


Corresponding author

Correspondence and reprint requests to: Joel Kramer, Psy.D., Memory and Aging Center, UCSF Medical Center, Box 1207, 350 Parnassus, Suite 706, San Francisco, CA 94143, USA. E-mail:


Hide All


Anderson, C.V., Bigler, E.D., & Blatter, D.D. (1995). Frontal lobe lesions, diffuse damage, and neuropsychological functioning in traumatic brain-injured patients. Journal of Clinical and Experimental Neuropsychology, 17, 900908.
Anderson, S.W., Damasio, H., Jones, R.D., & Tranel, D. (1991). Wisconsin Card Sorting Test performance as a measure of frontal lobe damage. Journal of Clinical and Experimental Neuropsychology, 13, 909922.
Andreasen, N.C., Rajarethinam, R., Cizadlo, T., Arndt, S., Swayze, V.W., Jr., Flashman, L.A., O'Leary, D.S., Ehrhardt, J.C., & Yuh, W.T. (1996). Automatic atlas-based volume estimation of human brain regions from MR images. Journal of Computer Assisted Tomography, 20, 98106.
Arbuthnott, K. & Frank, J. (2000). Trail Making Test, part B as a measure of executive control: Validation using a set-switching paradigm. Journal of Clinical and Experimental Neuropsychology, 22, 518528.
Aron, A.R., Monsell, S., Sahakian, B.J., & Robbins, T.W. (2004). A componential analysis of task-switching deficits associated with lesions of left and right frontal cortex. Brain, 127(Pt. 7), 15611573.
Barcelo, F. & Santome-Calleja, A. (2000). [A critical review of the specificity of the Wisconsin Card Sorting Test for the assessment of prefrontal function]. Revista de Neurologia, 30, 855864.
Brass, M., Ullsperger, M., Knoesche, T.R., von Cramon, D.Y., & Phillips, N.A. (2005). Who comes first? The role of the prefrontal and parietal cortex in cognitive control. Journal of Cognitive Neuroscience, 17, 13671375.
Cannon, T.D., Glahn, D.C., Kim, J., Van Erp, T.G., Karlsgodt, K., Cohen, M.S., Nuechterlein, K.H., Bava, S., & Shirinyan, D. (2005). Dorsolateral prefrontal cortex activity during maintenance and manipulation of information in working memory in patients with schizophrenia. Archives of General Psychiatry, 62, 10711080.
Crossley, M., Hiscock, M., & Foreman, J.B. (2004). Dual-task performance in early stage dementia: Differential effects for automatized and effortful processing. Journal of Clinical and Experimental Neuropsychology, 26, 332346.
Cummings, J.L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D.A., & Gornbein, J. (1994). The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia. Neurology, 44, 23082314.
Delis, D., Kaplan, E.B., & Kramer, J. (2001). The Delis–Kaplan Executive Function System. San Antonio, TX: The Psychological Corporation.
Derrfuss, J., Brass, M., Neumann, J., & von Cramon, D.Y. (2005). Involvement of the inferior frontal junction in cognitive control: Meta-analyses of switching and Stroop studies. Hum Brain Mapp, 25, 2234.
Funahashi, S. (2005). Prefrontal cortex and working memory processes. Neuroscience, 139, 251261.
Hanninen, T., Hallikainen, M., Koivisto, K., Partanen, K., Laakso, M.P., Riekkinen, P.J., Sr., & Soininen, H. (1997). Decline of frontal lobe functions in subjects with age-associated memory impairment. Neurology, 48, 148153.
Harris, G., Andreasen, N.C., Cizadlo, T., Bailey, J.M., Bockholt, H.J., Magnotta, V.A., & Arndt, S. (1999). Improving tissue classification in MRI: A three-dimensional multispectral discriminant analysis method with automated training class selection. Journal of Computer Assisted Tomography, 23, 144154.
Heaton, R.K. (1993). Wisconsin Card Sorting Test manual. Odessa, FL: Psychological Assessment Resources.
Jones-Gotman, M. (1991). Localization of lesions by neuropsychological testing. Epilepsia, 32(Suppl. 5), S41S52.
Konishi, S., Hayashi, T., Uchida, I., Kikyo, H., Takahashi, E., & Miyashita, Y. (2002). Hemispheric asymmetry in human lateral prefrontal cortex during cognitive set shifting. Proceedings of the National Academy of Science of the United States of America, 99, 78037808.
Levine, B., Stuss, D.T., & Milberg, W.P. (1995). Concept generation: Validation of a test of executive functioning in a normal aging population. Journal of Clinical and Experimental Neuropsychology, 17, 740758.
Magnotta, V.A., Harris, G., Andreasen, N.C., O'Leary, D.S., Yuh, W.T., & Heckel, D. (2002). Structural MR image processing using the BRAINS2 toolbox. Computerized Medical Imaging and Graphics, 26, 251264.
McDonald, C.R., Delis, D.C., Norman, M.A., Tecoma, E.S., & Iragui, V.J. (2005a). Discriminating patients with frontal-lobe epilepsy and temporal-lobe epilepsy: Utility of a multilevel design fluency test. Neuropsychology, 19, 806813.
McDonald, C.R., Delis, D.C., Norman, M.A., Tecoma, E.S., & Iragui-Madozi, V.I. (2005b). Is impairment in set-shifting specific to frontal-lobe dysfunction? Evidence from patients with frontal-lobe or temporal-lobe epilepsy. Journal of the International Neuropsychological Society, 11, 477481.
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E.M. (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.
Mendez, M.F., Selwood, A., Mastri, A.R., & Frey, W.H., Jr. (1993). Pick's disease versus Alzheimer's disease: A comparison of clinical characteristics. Neurology, 43, 289292.
Miyake, A., Friedman, N.P., Emerson, M.J., Witzki, A.H., Howerter, A., & Wager, T.D. (2000). The unity and diversity of executive functions and their contributions to complex “Frontal Lobe” tasks: A latent variable analysis. Cognitive Psychology, 41, 49100.
Moll, J., de Oliveira-Souza, R., Moll, F.T., Bramati, I.E., & Andreiuolo, P.A. (2002). The cerebral correlates of set-shifting: an fMRI study of the Trail Making Test. Arquivos de Neuro-psiquiatria, 60, 900905.
Monsell, S. (2003). Task switching. Trends in Cognitive Science, 7, 134140.
Nakahara, K., Hayashi, T., Konishi, S., & Miyashita, Y. (2002). Functional MRI of macaque monkeys performing a cognitive set-shifting task. Science, 295, 15321536.
Neary, D., Snowden, J.S., Gustafson, L., Passant, U., Stuss, D., Black, S., Freedman, M., Kertesz, A., Robert, P.H., Albert, M., Boone, K., Miller, B.L., Cummings, J., & Benson, D.F. (1998). Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria. Neurology, 51, 15461554.
Neary, D., Snowden, J.S., & Mann, D.M. (2000). Classification and description of frontotemporal dementias. Annals of the New York Academy of Science, 920, 4651.
Pantelis, C., Barber, F.Z., Barnes, T.R., Nelson, H.E., Owen, A.M., & Robbins, T.W. (1999). Comparison of set-shifting ability in patients with chronic schizophrenia and frontal lobe damage. Schizophrenia Research, 37, 251270.
Petrides, M. (2005). Lateral prefrontal cortex: Architectonic and functional organization. Philosophical Transactions of the Royal Society of London Series B Biological Science, 360, 781795.
Ravizza, S.M. & Ciranni, M.A. (2002). Contributions of the prefrontal cortex and basal ganglia to set shifting. Journal of Cognitive Neuroscience, 14, 472483.
Reitan, R.M. & Wolfson, D. (1995). Category Test and Trail Making Test as measures of frontal lobe functions. The Clinical Neuropsychologist, 9, 5056.
Rogers, R.D., Andrews, T.C., Grasby, P.M., Brooks, D.J., & Robbins, T.W. (2000). Contrasting cortical and subcortical activations produced by attentional-set shifting and reversal learning in humans. Journal of Cognitive Neuroscience, 12, 142162.
Shafritz, K.M., Kartheiser, P., & Belger, A. (2005). Dissociation of neural systems mediating shifts in behavioral response and cognitive set. Neuroimage, 25, 600606.
Stuss, D.T., Bisschop, S.M., Alexander, M.P., Levine, B., Katz, D., & Izukawa, D. (2001). The Trail Making Test: A study in focal lesion patients. Psychological Assessment, 13, 230239.
Talairach, J. & Tournoux, P. (1988). Co-planar stereotaxic atlas of the human brain: 3-dimensional proportional system; An approach to cerebral imaging. Stuttgart, Germany: George Thieme Verlag.
Varney, N.R., Roberts, R.J., Struchen, M.A., Hanson, T.V., Franzen, K.M., & Connell, S.K. (1996). Design fluency among normals and patients with closed head injury. Archives of Clinical Neuropsychology, 11, 345353.
Wager, T.D., Jonides, J., & Reading, S. (2004). Neuroimaging studies of shifting attention: A meta-analysis. Neuroimage, 22, 16791693.
Woods, R.P., Cherry, S.R., & Mazziotta, J.C. (1992). Rapid automated algorithm for aligning and reslicing PET images. Journal of Computer Assisted Tomography, 16, 620633.
Zakzanis, K.K., Mraz, R., & Graham, S.J. (2005). An fMRI study of the Trail Making Test. Neuropsychologia, 43, 18781886.


Magnetic resonance imaging correlates of set shifting



Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed