Spontaneous Brain Activity in the Default Mode Network Is Sensitive to Different Resting-State Conditions with Limited Cognitive Load

Background Recent functional MRI (fMRI) studies have demonstrated that there is an intrinsically organized default mode network (DMN) in the resting brain, primarily made up of the posterior cingulate cortex (PCC) and the medial prefrontal cortex (MPFC). Several previous studies have found that the DMN is minimally disturbed during different resting-state conditions with limited cognitive demand. However, this conclusion was drawn from the visual inspection of the functional connectivity patterns within the DMN and no statistical comparison was performed. Methodology/Principal Findings Four resting-state fMRI sessions were acquired: 1) eyes-closed (EC) (used to generate the DMN mask); 2) EC; 3) eyes-open with no fixation (EO); and 4) eyes-open with a fixation (EO-F). The 2–4 sessions were counterbalanced across participants (n = 20, 10 males). We examined the statistical differences in both functional connectivity and regional amplitude of low frequency fluctuation (ALFF) within the DMN among the 2–4 resting-state conditions (i.e., EC, EO, and EO-F). Although the connectivity patterns of the DMN were visually similar across these three different conditions, we observed significantly higher functional connectivity and ALFF in both the EO and the EO-F conditions as compared to the EC condition. In addition, the first and second resting EC conditions showed significant differences within the DMN, suggesting an order effect on the DMN activity. Conclusions/Significance Our findings of the higher DMN connectivity and regional spontaneous activities in the resting state with the eyes open suggest that the participants might have more non-specific or non-goal-directed visual information gathering and evaluation, and mind wandering or daydreaming during the resting state with the eyes open as compared to that with the eyes closed, thus providing insights into the understanding of unconstrained mental activity within the DMN. Our results also suggest that it should be cautious when choosing the type of a resting condition and designating the order of the resting condition in multiple scanning sessions in experimental design.

[1]  V. Calhoun,et al.  Aberrant "default mode" functional connectivity in schizophrenia. , 2007, The American journal of psychiatry.

[2]  P. Fransson.  Spontaneous low‐frequency BOLD signal fluctuations: An fMRI investigation of the resting‐state default mode of brain function hypothesis , 2005, Human brain mapping.

[3]  B. Mazoyer,et al.  Cortical networks for working memory and executive functions sustain the conscious resting state in man , 2001, Brain Research Bulletin.

[4]  M. Fox,et al.  Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging , 2007, Nature Reviews Neuroscience.

[5]  Wang Zhan,et al.  Group independent component analysis reveals consistent resting-state networks across multiple sessions , 2008, Brain Research.

[6]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[7]  M. Greicius,et al.  Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI , 2004, Proc. Natl. Acad. Sci. USA.

[8]  B. Biswal,et al.  The resting brain: unconstrained yet reliable. , 2009, Cerebral cortex.

[9]  M. Fukunaga,et al.  Low frequency BOLD fluctuations during resting wakefulness and light sleep: A simultaneous EEG‐fMRI study , 2008, Human brain mapping.

[10]  Y. Zang,et al.  Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI , 2007, Brain and Development.

[11]  Bart Rypma,et al.  Hemodynamic scaling of fMRI-BOLD signal: validation of low-frequency spectral amplitude as a scalability factor. , 2007, Magnetic resonance imaging.

[12]  P. Fransson.  How default is the default mode of brain function? Further evidence from intrinsic BOLD signal fluctuations , 2006, Neuropsychologia.

[13]  R. Bluhm,et al.  Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network. , 2007, Schizophrenia bulletin.

[14]  Bharat Biswal,et al.  Slow vasomotor fluctuation in fMRI of anesthetized child brain , 2000, Magnetic resonance in medicine.

[15]  Tianzi Jiang,et al.  Regional coherence changes in the early stages of Alzheimer’s disease: A combined structural and resting-state functional MRI study , 2007, NeuroImage.

[16]  Justin L. Vincent,et al.  Intrinsic functional architecture in the anaesthetized monkey brain , 2007, Nature.

[17]  Florin Dolcos,et al.  Similarities and Differences in the Neural Correlates of Episodic Memory Retrieval and Working Memory , 2002, NeuroImage.

[18]  R W Cox,et al.  AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. , 1996, Computers and biomedical research, an international journal.

[19]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[20]  Tianzi Jiang,et al.  Enhanced resting-state brain activities in ADHD patients: A fMRI study , 2008, Brain and Development.

[21]  N. Logothetis,et al.  Neurophysiological investigation of the basis of the fMRI signal , 2001, Nature.

[22]  M. Greicius,et al.  Default-Mode Activity during a Passive Sensory Task: Uncoupled from Deactivation but Impacting Activation , 2004, Journal of Cognitive Neuroscience.

[23]  David J. Foster,et al.  Reverse replay of behavioural sequences in hippocampal place cells during the awake state , 2006, Nature.

[24]  Chaozhe Zhu,et al.  Amplitude of low frequency fluctuation within visual areas revealed by resting-state functional MRI , 2007, NeuroImage.

[25]  S. Rombouts,et al.  Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: An fMRI study , 2005, Human brain mapping.

[26]  Yong He,et al.  Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI. , 2007, Brain & development.

[27]  M. Raichle,et al.  Searching for a baseline: Functional imaging and the resting human brain , 2001, Nature Reviews Neuroscience.

[28]  Peter A. Bandettini,et al.  Separating respiratory-variation-related fluctuations from neuronal-activity-related fluctuations in fMRI , 2006, NeuroImage.

[29]  M. Torrens.  Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[30]  M. Corbetta,et al.  Common Blood Flow Changes across Visual Tasks: II. Decreases in Cerebral Cortex , 1997, Journal of Cognitive Neuroscience.

[31]  Vinod Menon,et al.  Functional connectivity in the resting brain: A network analysis of the default mode hypothesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  G. Pelled,et al.  Different physiological MRI noise between cortical layers , 2004, Magnetic resonance in medicine.

[33]  M. Raichle,et al.  Emotion-induced changes in human medial prefrontal cortex: I. During cognitive task performance. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Bharat B. Biswal,et al.  Detection and scaling of task-induced fMRI-BOLD response using resting state fluctuations , 2008, NeuroImage.

[35]  B. Biswal,et al.  Cingulate-Precuneus Interactions: A New Locus of Dysfunction in Adult Attention-Deficit/Hyperactivity Disorder , 2008, Biological Psychiatry.

[36]  P. Roland,et al.  Estimation of the Probabilities of 3D Clusters in Functional Brain Images , 1998, NeuroImage.

[37]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[38]  B. Biswal,et al.  Cocaine administration decreases functional connectivity in human primary visual and motor cortex as detected by functional MRI , 2000, Magnetic resonance in medicine.

[39]  Liang Wang,et al.  Default mode network as revealed with multiple methods for resting-state functional MRI analysis , 2008, Journal of Neuroscience Methods.

[40]  Scott T. Grafton,et al.  Response to Comment on "Wandering Minds: The Default Network and Stimulus-Independent Thought" , 2007, Science.

[41]  J. A. Frost,et al.  Conceptual Processing during the Conscious Resting State: A Functional MRI Study , 1999, Journal of Cognitive Neuroscience.

[42]  Keith A. Johnson,et al.  Cortical Hubs Revealed by Intrinsic Functional Connectivity: Mapping, Assessment of Stability, and Relation to Alzheimer's Disease , 2009, The Journal of Neuroscience.

[43]  Kuncheng Li,et al.  Altered functional connectivity in early Alzheimer's disease: A resting‐state fMRI study , 2007, Human brain mapping.

[44]  M. Raichle,et al.  Emotion-induced changes in human medial prefrontal cortex: II. During anticipatory anxiety. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Scott T Grafton,et al.  Medial temporal lobe BOLD activity at rest predicts individual differences in memory ability in healthy young adults , 2008, Proceedings of the National Academy of Sciences.

[46]  G. Shulman,et al.  Medial prefrontal cortex and self-referential mental activity: Relation to a default mode of brain function , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[47]  B. Biswal,et al.  Functional connectivity in the motor cortex of resting human brain using echo‐planar mri , 1995, Magnetic resonance in medicine.

[48]  M. Lowe,et al.  Functional Connectivity in Single and Multislice Echoplanar Imaging Using Resting-State Fluctuations , 1998, NeuroImage.

[49]  Clara A. Scholl,et al.  Synchronized delta oscillations correlate with the resting-state functional MRI signal , 2007, Proceedings of the National Academy of Sciences.

[50]  Bernard R. Rosner,et al.  Fundamentals of Biostatistics. , 1992 .

[51]  Yingli Lu,et al.  Regional homogeneity approach to fMRI data analysis , 2004, NeuroImage.

[52]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[53]  B. Biswal,et al.  Network homogeneity reveals decreased integrity of default-mode network in ADHD , 2008, Journal of Neuroscience Methods.