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Parametric manipulation of working memory load in traumatic brain injury: Behavioral and neural correlates



Traumatic brain injury (TBI) is often associated with enduring impairments in high-level cognitive functioning, including working memory (WM). We examined WM function in predominantly chronic patients with mild, moderate and severe TBI and healthy comparison subjects behaviorally and, in a small subset of moderate-to-severe TBI patients, with event-related functional magnetic resonance imaging (fMRI), using a visual n-back task that parametrically varied WM load. TBI patients showed severity-dependent and load-related WM deficits in performance accuracy, but not reaction time. Performance of mild TBI patients did not differ from controls; patients with moderate and severe TBI were impaired, relative to controls and mild TBI patients, but only at higher WM-load levels. fMRI results show that TBI patients exhibit altered patterns of activation in a number of WM-related brain regions, including the dorsolateral prefrontal cortex and Broca's area. Examination of the pattern of behavioral responding and the temporal course of activations suggests that WM deficits in moderate-to-severe TBI are due to associative or strategic aspects of WM, and not impairments in active maintenance of stimulus representations. Overall, results demonstrate that individuals with moderate-to-severe TBI exhibit WM deficits that are associated with dysfunction within a distributed network of brain regions that support verbally mediated WM. (JINS, 2004, 10, 724–741.)


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Reprint requests to: William M. Perlstein, Ph.D., Department of Clinical and Health Psychology, HSC Box 100165, University of Florida, Gainesville, FL 32610. E-mail:


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Adams, K.M., Brown, G.G., & Grant, I. (1985). Analysis of covariance as a remedy for demographic mismatch of research subject groups: Some sobering simulations. Journal of Clinical and Experimental Neuropsychology, 7, 445462.
Adams, J.H., Scott, G., Parker, L.S., Graham, D.I., & Doyle, D. (1980). The contusion index: A quantitative approach to cerebral contusions in head injury. Neuropathology and Applied Neurobiology, 6, 319324.
American Congress of Rehabilitative Medicine. (1993). Definition of mild traumatic brain injury. Journal of Head Trauma Rehabilitation, 8, 8687.
Baddeley, A.D. (1986). Working memory. New York: Oxford University Press.
Beck, A.T., Ward, C.H., Mendelson, M., Mock, J.E., & Erbaugh, J.K. (1961). An inventory for measuring depression. Archives of General Psychiatry, 4, 561571.
Bigler, E.D. (1990). Neuropathology of traumatic brain injury. In E.D. Bigler (Ed.), Traumatic Brain Injury (pp. 1349). Austin, TX: Pro-ed.
Blair, J.R. & Spreen, O. (1989). Predicting premorbid IQ: A revision of the National Adult Reading Test. Clinical Neuropsychologist, 3, 129136.
Bond, M.R., (1986). Neurobehavioral sequelae of closed head injury. In I. Grant & K.M. Adams (Eds.), Neuropsychological Assessment of Neuropsychological Disorders (pp. 347373). New York: Oxford University Press.
Braver, T.S., Cohen, J.D., Nystrom, L.E., Jonides, J., Smith, E.E., & Noll, D.C. (1997). A parametric study of prefrontal cortex involvement in human working memory. Neuroimage, 5, 4962.
Braver, S.L. & Sheets, V.L. (1993). Monotonic hypothesis in multiple group designs: A Monte Carlo study. Psychological Bulletin, 113, 379395.
Bublak, P., Schubert, T., Matthes-von Cramon, G., and von Cramon, D.Y. (2000). Differential demands on working memory for guiding a simple action sequence: Evidence from closed-head-injured subjects. Journal of Clinical and Experimental Neuropsychology, 22, 176189.
Burgess, P.W. (1997). Theory and methodology in executive function research. In P. Rabbitt (Ed.), Methodology of frontal and executive function (pp. 81116). Hove, UK: Psychology Press.
Callicott, J.J., Mattay, V.S., Bertolino, A., Finn, K., Coppola, R., Frank, J.A., Goldberg, T.E., & Weinberger, D.R. (1999). Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. Cerebral Cortex, 9, 2026.
Chapman, L.J. & Chapman, J.P. (1989). Strategies for resolving the heterogeneity of schizophrenia and their relatives using cognitive measures. Journal of Abnormal Psychology, 98, 357366.
Christodoulou, C., DeLuca, J., Ricker, J.H., Madigan, N.K., Bly, B.M., Lange, G., Kalnin, A.J., Liu, W-C., Steffner, J., Diamond, B.J., & Ni, A.C. (2001). Functional magnetic resonance imaging of working memory impairment after traumatic brain injury. Journal of Neurology, Neurosurgery and Psychiatry, 71, 161168.
Cicerone, K.D. (1996). Attention deficits and dual task demands after mild traumatic brain injury. Brain Injury, 10, 7989.
Cohen, J.D., Forman, S.D., Braver, T.S., Casey, B.J., Servan-Schreiber, D., & Noll, D.C. (1994). Activation of the prefrontal cortex in a nonspatial working memory task with functional MRI. Human Brain Mapping, 1, 293304.
Cohen, J.D., Macwhinney, B., Flatt, M.R., & Provost, J. (1993). PsyScope: A new graphic interactive environment for designing psychology experiments. Behavioral Research Methods, Instruments and Computers, 25, 257271.
Cohen, J.D., Perlstein, W.M., Braver, T.S., Nystrom, L.E., Noll, D.C., Jonides, J., & Smith, E.E. (1997). Temporal dynamics of brain activation during a working memory task. Nature, 386, 604608.
Courtney, S.M., Ungerleider, L.G., Keil, K., & Haxby, J.V. (1997). Transient and sustained activity in a distributed neural system for human working memory. Nature, 386, 608612.
Cox, R.W. (1996). AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages. Computational and Biomedical Research, 29, 162173.
D'Esposito, M., Detre, J.A., Alsop, D.C., Shin, R.K., Atlas, S., & Grossman, M. (1995). The neural basis of the central executive system of working memory. Nature, 378, 279281.
Dreher, J.-C. & Grafman, J. (2003). Dissociating the roles of the rostral anterior cingulate and the lateral prefrontal cortices in performing two tasks simultaneously or successively. Cerebral Cortex, 13, 329339.
Ferraro, F.R. (1996). Cognitive slowing in closed-head injury. Brain and Cognition, 32, 429440.
Forman, S.D., Cohen, J.D., Fitzgerald, M., Eddy, W.F., Mintun, M.A., & Noll, D.C. (1995). Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): Use of a cluster-size threshold. Magnetic Resonance in Medicine, 33, 636647.
Goldman-Rakic, P. (1987). Circuitry of primate prefrontal cortex and regulation of behavior by representational memory (pp. 373417). In F. Plum & V. Mountcastle (Eds.), Handbook of Physiology—The Nervous System V. Bethesda, MD: American Physiological Society.
Greve, K.W., Love, J.M., Sherwin, E., Mathias, C.W., Ramzinski, P., & Levy, J. (2002). Wisconsin Card Sorting Test in chronic severe traumatic brain injury: Factor structure and performance subgroups. Brain Injury, 16, 2940.
Gronwall, D. (1986). Rehabilitation programs for patients with mild head injury: Components, problems, and evaluation. Journal of Head Trauma and Rehabilitation, 1, 153162.
Humphreys, M.S. & Revelle, W. (1984). Personality, motivation, and performance: a theory of the relationship between individual differences and information processing. Psychological Review, 91, 153184.
Huynh, H. & Feldt, L.S. (1976). Estimation of the box correction for degrees of freedom from sample data in the randomized block and split-plot designs. Journal of Educational Statistics, 1, 6982.
Jonides, J. & Smith, E.E. (1997). The architecture of working memory. In M.D. Rugg (Ed.), Cognitive neuroscience (pp. 243276). Cambridge, MA: MIT Press.
Keppel, G. (1982). Design and analysis: A Researchers Handbook (2nd ed.). Englewood Cliffs, NJ: Prentice Hall.
Leclercq, M., Couillet, J., Azouvi, P., Marlier, N., Martin, Y., Strypstein, E., & Rousseaux, M. (2000). Dual task performance after severe diffuse traumatic brain injury or vascular prefrontal damage. Journal of Experimental and Clinical Neuropsychology, 22, 339350.
Levin, H.S., Gary, H., Eisenberg, H., Ruff, R., Barth, J., Kreutzer, J., High, W., Portman, S., Foulkes, M., & Jane, J. (1990). Neurobehavioral outcome 1-year after severe head injury: Experience of the Traumatic Coma Data Bank. Journal of Neurosurgery, 73, 699709.
Lezak, M.D. (1995). Neuropsychological assessment (3rd ed.). New York: Oxford Press.
McAllister, T.W., Sparling, M.B., Flashman, L.A., Guerin, S.J., Mamourian, A.C., & Saykin, A.J. (2001). Differential working memory load effects after mild traumatic brain injury. Neuroimage, 14, 10041012.
McAllister, T.W., Saykin, A.J., Flashman, L.A., Sparling, M.B., Johnson, S.C., Guerin, S.J., Mamourian, A.C., Weaver, J.B., & Yanofsky, N. (1999). Brain activation during working memory 1 month after mild traumatic brain injury: A functional MRI study. Neurology, 53, 13001308.
McDowell, S., Whyte, J., & D'Esposito, M. (1997). Working memory impairments in traumatic brain injury: Evidence from a dual-task paradigm. Neuropsychologia, 35, 13411353.
McDowell, S., Whyte, J., & D'Esposito, M. (1998). Differential effect of a dopaminergic agonist on prefrontal function in traumatic brain injury patients. Brain, 121, 11551164.
McKinlay, W.W., Brooks, D.N., Bond, M.R., Marinage, D.P., & Marshall, M.M. (1981). The short-term outcome of severe blunt head injury as reported by relatives of the injured persons. Journal of Neurology, Neurosurgery, and Psychiatry, 44, 527533.
Miller, E. (1970). Simple and choice reaction-time following severe head injury. Cortex, 6, 121127.
Miller, G.A. & Chapman, J.P. (2001). Commentary on two articles concerning generalized and specific cognitive deficits. Journal of Abnormal Psychology, 110, 3139.
Miyake, A., Friedman, N.P., Emerson, M.J., Witzki, A.H., Howerter, A., & Wager, T. (2000). The unity and diversity of executive functions and their contributions to complex “frontal lobe” tasks: A latent variable analysis. Cognitive Psychology, 41, 49100.
Miyake, A., Emerson, M.J., & Friedman, N.P. (2000). Assessment of executive functions in clinical settings: Problems and recommendations. Seminars in Speech and Language, 21, 169183
Noll, D.C., Cohen, J.D., Meyer, C.H., & Schneider, W. (1995). Spiral K-space MR imaging of cortical activity. Journal of Magnetic Resonance Imaging, 5, 4956.
Norman, D.A. & Shallice, T. (1986). Attention to action: Willed and automatic control of behavior. In R.J. Davidson, G.E. Schwartz, & D. Shapiro (Eds.), Consciousness and self-regulation: Advances in research and theory (Vol. 4, pp. 118). New York: Plenum.
Park, N.W., Moscovitch, M., & Robertson, I.H. (1999). Divided attention impairments after traumatic brain injury. Neuropsychologia, 37, 11191133.
Pashler, H. (1994). Dual-task interference in simple tasks: Data and theory. Psychological Bulletin, 116, 220244.
Perlstein, W.M., Carter, C.S., Noll, D.C., & Cohen, J.D. (2001). Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia. American Journal of Psychiatry, 158, 11051113.
Perlstein, W.M., Cole, M.A., Larson, M., Kelly, K., Seignourel, P., & Keil, A. (2003a). Steady-state visual evoked potentials reveal frontally-mediated working memory activity in humans. Steady-state visual evoked potentials reveal frontally-mediated working memory activity in humans. Neuroscience Letters, 342, 191195.
Perlstein, W.M., Dixit, N.K., Carter, C.S., Noll, D.C., & Cohen, J.D. (2003b). Prefrontal cortex dysfunction mediates deficits in working memory and prepotent responding in schizophrenia. Biological Psychiatry, 53, 2538.
Phillips, L.H. (1997). Do “frontal tests” measure executive function? Issues of assessment and evidence from fluency tests. In P. Rabbitt (Ed.), Methodology of frontal and executive function (pp. 191213). Hove, UK: Psychology Press.
Ponsford, J.L. & Kinsella, G. (1992). Attentional deficits following closed head injury. Journal of Clinical and Experimental Neuropsychology, 14, 822838.
Ponsford, J.L., Olver, J.H., & Curran, C. (1995). A profile of outcome: 2 years after traumatic brain injury. Brain Injury, 9, 110.
Price, C.J. & Friston, K.J. (1999). Scanning patients with tasks they can perform. Human Brain Mapping, 8, 102108.
Price, C.J. & Friston, K.J. (2001). Functional neuroimaging of neuropsychologically impaired patients. In R. Cabeza & A. Kingstone (Eds.), Handbook of functional neuroimaging of cognition (pp. 379399). Cambridge, MA: MIT Press.
Salthouse, T.A. (1996). The processing-speed theory of adult age differences in cognition. Psychological Review, 103, 403428.
Shallice, T. & Burgess, P. (1996). The domain of supervisory processes and temporal organization of behavior. Philosophical Transactions of the Royal Society of London B, Biological Sciences, 351, 14051411.
Smith, E.E. & Jonides, J. (1998). Neuroimaging analysis of human working memory. Proceedings of the National Academy of Sciences, 25, 1206112068.
Spielberger, C.D., Gorsuch, R.L., & Lushene, R.E. (1970). Manual for the state-trait anxiety inventory. Palo Alto, CA: Consulting Psychologists Press.
Strauss, M.E. (2001). Demonstrating specific cognitive deficits: A psychometric perspective. Journal of Abnormal Psychology, 110, 614.
Stuss, D.T. & Alexander, M.P. (2000). Executive functions and the frontal lobes: A conceptual view. Psychological Research, 63, 289298.
Stuss, D.T. & Levine, B. (2002). Adult clinical neuropsychology: Lessons from studies of the frontal lobes. Annual Reviews of Psychology, 53, 401433.
Szameitat, A.J., Schubert, T., Müller, K., & von Cramon, D.Y. (2002). Localization of executive functions in dual-task performance with fMRI. Journal of Cognitive Neuroscience, 14, 11841199.
Talairach, J. & Tournoux, P. (1988). Co-planar stereotaxic atlas of the human brain. Stuttgart, Germany: George Thieme Verlag.
Teasdale, G. & Jennett, B. (1974). Assessment of coma and impaired consciousness: A practical scale. Lancet, ii, 8184.
Van Zomeren, A.H. & Brouwer, W.H. (1987). Head injury and concepts of attention. In H.S. Levin, J. Grafman, & H. Eisenberg (Eds.), Neurobehavioral recovery from head injury, pp. 398415. New York: Oxford University Press.
Weinberger, D.R. & Berman, K.F. (1996). Prefrontal function in schizophrenia: Confounds and controversies. Philosophical Transactions of the Royal Society of London B, 351, 14951503.
Wiegner, S. & Donders, J. (1999). Performance on the Wisconsin Card Sorting Test after traumatic brain injury. Assessment, 6, 179187.
Woods, R.P., Cherry, S.R., & Maziotta, J.C. (1992). Rapid automation algorithm for aligning and reslicing PET images. Journal of Computer Assisted Tomography, 16, 620633.


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