Effects of Verbal Working Memory Load on Corticocortical Connectivity Modeled by Path Analysis of Functional Magnetic Resonance Imaging Data

We investigated the hypothesis that there are load-related changes in the integrated function of frontoparietal working memory networks. Functional magnetic resonance imaging time-series data from 10 healthy volunteers performing a graded n-back verbal working memory task were modeled using path analysis. Seven generically activated regions were included in the model: left/right middle frontal gyri (L/R MFG), left/right inferior frontal gyri (L/R IFG), left/right posterior parietal cortex (L/R PPC), and supplementary motor area (SMA). The model provided a good fit to the 1-back (chi(2) = 7.04, df = 8, P = 0.53) and 2-back conditions (chi(2) = 9.35, df = 8, P = 0.31) but not for the 3-back condition (chi(2) = 20.60, df = 8, P = 0.008). Model parameter estimates were compared overall among conditions: there was a significant difference overall between 1-back and 2-back conditions (chi(2)(diff) = 74.77, df = 20, P < 0.001) and also between 2-back and 3-back conditions (chi(2)(diff) = 96.28, df = 20, P < 0.001). Path coefficients between LIFG and LPPC were significantly different from zero in both 1-back and 2-back conditions; in the 2-back condition, additional paths from LIFG to LPPC via SMA and to RMFG from LMFG and LPPC were also nonzero. This study demonstrated a significant change in functional integration of a neurocognitive network for working memory as a correlate of increased load. Enhanced inferior frontoparietal and prefrontoprefrontal connectivity was observed as a correlate of increasing memory load, which may reflect greater demand for maintenance and executive processes, respectively.

[1]  Karl J. Friston,et al.  Assessing interactions among neuronal systems using functional neuroimaging , 2000, Neural Networks.

[2]  Edward T. Bullmore,et al.  Prolonged Reaction Time to a Verbal Working Memory Task Predicts Increased Power of Posterior Parietal Cortical Activation , 2000, NeuroImage.

[3]  R. Coppola,et al.  Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. , 1999, Cerebral cortex.

[4]  Adrian M. Owen,et al.  The role of the lateral frontal cortex in mnemonic processing: the contribution of functional neuroimaging , 2000, Experimental Brain Research.

[5]  Karl J. Friston,et al.  Neural modeling and functional brain imaging: an overview , 2000, Neural Networks.

[6]  Karl J. Friston,et al.  Activation of the human hippocampal formation during auditory-verbal long-term memory function , 1993, Neuroscience Letters.

[7]  Karl J. Friston,et al.  Functional mapping of brain areas implicated in auditory--verbal memory function. , 1993, Brain : a journal of neurology.

[8]  M. D’Esposito,et al.  The neural basis of the central executive system of working memory , 1995, Nature.

[9]  Goldman-Rakic Ps Cellular and circuit basis of working memory in prefrontal cortex of nonhuman primates. , 1990 .

[10]  Alan C. Evans,et al.  Lateralization of phonetic and pitch discrimination in speech processing. , 1992, Science.

[11]  M D'Esposito,et al.  The roles of prefrontal brain regions in components of working memory: effects of memory load and individual differences. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  R. Henson,et al.  Frontal lobes and human memory: insights from functional neuroimaging. , 2001, Brain : a journal of neurology.

[13]  Jonathan D. Cohen,et al.  Dissociating working memory from task difficulty in human prefrontal cortex , 1997, Neuropsychologia.

[14]  Robert Sekuler,et al.  Corticolimbic Interactions Associated with Performance on a Short-Term Memory Task Are Modified by Age , 2000, The Journal of Neuroscience.

[15]  Edward E. Smith,et al.  Dissociation of Storage and Rehearsal in Verbal Working Memory: Evidence From Positron Emission Tomography , 1996 .

[16]  D. Manoach,et al.  Prefrontal cortex fMRI signal changes are correlated with working memory load , 1997, Neuroreport.

[17]  Edward E. Smith,et al.  A parametric study of prefrontal cortex involvement in human working memory , 1996, NeuroImage.

[18]  Leslie G. Ungerleider,et al.  Network analysis of cortical visual pathways mapped with PET , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  E. Bullmore,et al.  Functional Magnetic Resonance Image Analysis of a Large-Scale Neurocognitive Network , 1996, NeuroImage.

[20]  Richard S. J. Frackowiak,et al.  The neural correlates of the verbal component of working memory , 1993, Nature.

[21]  Robert H. Logie,et al.  Working Memory and Thinking: Current Issues In Thinking And Reasoning , 1998 .

[22]  B. J. Casey,et al.  Activation of the prefrontal cortex in a nonspatial working memory task with functional MRI , 1994, Human brain mapping.

[23]  T A Carpenter,et al.  Colored noise and computational inference in neurophysiological (fMRI) time series analysis: Resampling methods in time and wavelet domains , 2001, Human brain mapping.

[24]  E. Bullmore,et al.  Methods for diagnosis and treatment of stimulus‐correlated motion in generic brain activation studies using fMRI , 1999, Human brain mapping.

[25]  C Loehlin John,et al.  Latent variable models: an introduction to factor, path, and structural analysis , 1986 .

[26]  J. Desmond,et al.  Load-Dependent Roles of Frontal Brain Regions in the Maintenance of Working Memory , 1999, NeuroImage.

[27]  Richard Scheines,et al.  Discovering Causal Structure: Artificial Intelligence, Philosophy of Science, and Statistical Modeling , 1987 .

[28]  S C Williams,et al.  Generic brain activation mapping in functional magnetic resonance imaging: a nonparametric approach. , 1997, Magnetic resonance imaging.

[29]  P. Roland,et al.  Bilateral activation of fronto-parietal networks by incrementing demand in a working memory task. , 1997, Cerebral cortex.

[30]  T. Wan Structural Equation Models with Latent Variables , 2002 .

[31]  P. Goldman-Rakic,et al.  Interhemispheric integration: II. Symmetry and convergence of the corticostriatal projections of the left and the right principal sulcus (PS) and the left and the right supplementary motor area (SMA) of the rhesus monkey. , 1991, Cerebral cortex.

[32]  Edward E. Smith,et al.  Temporal dynamics of brain activation during a working memory task , 1997, Nature.

[33]  A. McIntosh,et al.  Understanding Neural Interactions in Learning and Memory Using Functional Neuroimaging , 1998, Annals of the New York Academy of Sciences.

[34]  Edward T. Bullmore,et al.  Does frontal lobe activation during retrieval reflect complexity of retrieved information? , 2000, Neuroreport.

[35]  M. Petrides The role of the mid-dorsolateral prefrontal cortex in working memory , 2000, Experimental Brain Research.

[36]  M. Young The organization of neural systems in the primate cerebral cortex , 1993, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[37]  P. Goldman-Rakic,et al.  Interhemispheric integration: I. Symmetry and convergence of the corticocortical connections of the left and the right principal sulcus (PS) and the left and the right supplementary motor area (SMA) in the rhesus monkey. , 1991, Cerebral cortex.

[38]  Karl G. Jöreskog,et al.  Lisrel 8: User's Reference Guide , 1997 .

[39]  C. Büchel,et al.  Modulation of connectivity in visual pathways by attention: cortical interactions evaluated with structural equation modelling and fMRI. , 1997, Cerebral cortex.

[40]  Edward E. Smith,et al.  Verbal Working Memory Load Affects Regional Brain Activation as Measured by PET , 1997, Journal of Cognitive Neuroscience.

[41]  E. Bullmore,et al.  How Good Is Good Enough in Path Analysis of fMRI Data? , 2000, NeuroImage.

[42]  Leslie G. Ungerleider,et al.  Changes in limbic and prefrontal functional interactions in a working memory task for faces. , 1996, Cerebral cortex.

[43]  John G. Taylor,et al.  Imaging and neural modelling in episodic and working memory processes , 2000, Neural Networks.

[44]  M. Just,et al.  Brain Activation Modulated by Sentence Comprehension , 1996, Science.

[45]  Karl J. Friston,et al.  Learning-related neuronal responses in prefrontal cortex studied with functional neuroimaging. , 1999, Cerebral cortex.

[46]  A. Satorra Structural Equation Models with Latent Variables , 2002 .

[47]  B. Postle,et al.  Prefrontal cortical contributions to working memory: evidence from event-related fMRI studies , 2000, Experimental Brain Research.

[48]  M M Mesulam,et al.  Large‐scale neurocognitive networks and distributed processing for attention, language, and memory , 1990, Annals of neurology.