The organization of intrinsic brain activity differs between genders: A resting‐state fMRI study in a large cohort of young healthy subjects

Objectives: To investigate, using resting state (RS) functional MRI (fMRI), gender‐related differences of functional connectivity (FC) and functional network connectivity (FNC) of the human brain. Experimental design: One‐hundred and four young healthy subjects (48/56 men/women), aged between 20 and 29 years, underwent a 10‐min RS fMRI acquisition. Independent component analysis (ICA) and statistical parametric mapping were used to assess gender‐related differences in RSNs, with and without correction for regional gray matter (GM) volume. The relationships among all RSNs was also assessed using a FNC method. Principal observations: For all networks, significant between‐group differences of RS activity were found. Between‐group comparisons of RSNs changed when adjusting for GM volume, as follows: (1) there was only marginal effect on the analysis of sensory (i.e., sensorimotor, visual, and auditory) networks; and (2) there was a significantly increased difference when cognitive networks (apart from one related to attention) were considered. Compared with women, men experienced increased FC in parietal and occipital regions in most RSNs, whereas women experienced a higher RS FC in frontal and temporal regions, and in the cerebellum. When compared to women, increased FNC was found in men between several cognitive and sensory networks, whereas women showed an increased FNC only between attention and right working‐memory networks. Conclusions: The organization of intrinsic FC and FNC differ between genders. The detected differences could contribute to the understanding of the known between‐gender variation in task‐related recruitments, and the patterns of abnormalities detected in neurologic and psychiatric diseases with a gender prevalence. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.

[1]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[2]  S. Rombouts,et al.  Consistent resting-state networks across healthy subjects , 2006, Proceedings of the National Academy of Sciences.

[3]  R. Cabeza,et al.  Imaging Cognition II: An Empirical Review of 275 PET and fMRI Studies , 2000, Journal of Cognitive Neuroscience.

[4]  Efstathios D. Gennatas,et al.  Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer's disease. , 2010, Brain : a journal of neurology.

[5]  G. Wilson,et al.  Sex, sexual orientation, and identification of positive and negative facial affect , 2004, Brain and Cognition.

[6]  Christian Windischberger,et al.  Toward discovery science of human brain function , 2010, Proceedings of the National Academy of Sciences.

[7]  Terrence J. Sejnowski,et al.  An Information-Maximization Approach to Blind Separation and Blind Deconvolution , 1995, Neural Computation.

[8]  Vince D. Calhoun,et al.  A method for functional network connectivity among spatially independent resting-state components in schizophrenia , 2008, NeuroImage.

[9]  Faith M. Gunning-Dixon,et al.  Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: replicability of regional differences in volume , 2004, Neurobiology of Aging.

[10]  Jorge Sepulcre,et al.  Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors , 2009, Proceedings of the National Academy of Sciences.

[11]  Aapo Hyvärinen,et al.  Validating the independent components of neuroimaging time series via clustering and visualization , 2004, NeuroImage.

[12]  S. Kitazawa,et al.  Sex differences in lateralization revealed in the posterior language areas. , 2000, Cerebral cortex.

[13]  John D E Gabrieli,et al.  Sex differences in the neural basis of emotional memories , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[14]  H. Critchley,et al.  Neural systems supporting interoceptive awareness , 2004, Nature Neuroscience.

[15]  J. Mcglone,et al.  Sex differences in the cerebral organization of verbal functions in patients with unilateral brain lesions. , 1977, Brain : a journal of neurology.

[16]  L. Katz,et al.  Sex differences in the functional organization of the brain for language , 1995, Nature.

[17]  H. Rusinek,et al.  Functional magnetic resonance imaging of human brain activity in a verbal fluency task , 1998, Journal of neurology, neurosurgery, and psychiatry.

[18]  J. Pekar,et al.  A method for making group inferences from functional MRI data using independent component analysis , 2001, Human brain mapping.

[19]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[20]  S. Bookheimer Functional MRI of language: new approaches to understanding the cortical organization of semantic processing. , 2002, Annual review of neuroscience.

[21]  A. Lundervold,et al.  Functional magnetic resonance imaging (fMRI) study of sex differences in a mental rotation task. , 2000, Medical science monitor : international medical journal of experimental and clinical research.

[22]  B. McEwen,et al.  Clinically relevant basic science studies of gender differences and sex hormone effects. , 1998, Psychopharmacology bulletin.

[23]  Abraham Z. Snyder,et al.  A default mode of brain function: A brief history of an evolving idea , 2007, NeuroImage.

[24]  J. Gao,et al.  Neural activities associated with emotion recognition observed in men and women , 2005, Molecular Psychiatry.

[25]  M. Goodale,et al.  Two visual systems re-viewed , 2008, Neuropsychologia.

[26]  M. Mesulam,et al.  The Insula of Reil in Man and Monkey , 1985 .

[27]  M. Goodale,et al.  An evolving view of duplex vision: separate but interacting cortical pathways for perception and action , 2004, Current Opinion in Neurobiology.

[28]  Ramon Casanova,et al.  Biological parametric mapping: A statistical toolbox for multimodality brain image analysis , 2007, NeuroImage.

[29]  Jean-Luc Anton,et al.  Region of interest analysis using an SPM toolbox , 2010 .

[30]  Michael X. Cohen,et al.  Interference of working memory load with long‐term memory formation , 2009, The European journal of neuroscience.

[31]  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.

[32]  Stephen M. Smith,et al.  Accurate, Robust, and Automated Longitudinal and Cross-Sectional Brain Change Analysis , 2002, NeuroImage.

[33]  Stephen M. Smith,et al.  fMRI resting state networks define distinct modes of long-distance interactions in the human brain , 2006, NeuroImage.

[34]  John Ashburner,et al.  A fast diffeomorphic image registration algorithm , 2007, NeuroImage.

[35]  J L Lancaster,et al.  Automated Talairach Atlas labels for functional brain mapping , 2000, Human brain mapping.

[36]  V. Calhoun,et al.  Aberrant localization of synchronous hemodynamic activity in auditory cortex reliably characterizes schizophrenia , 2004, Biological Psychiatry.

[37]  André Aleman,et al.  Do women really have more bilateral language representation than men? A meta-analysis of functional imaging studies. , 2004, Brain : a journal of neurology.

[38]  Heike Schmidt,et al.  No gender differences in brain activation during the N‐back task: An fMRI study in healthy individuals , 2009, Human brain mapping.

[39]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[40]  Yong He,et al.  Spatial patterns of intrinsic brain activity in mild cognitive impairment and alzheimer's disease: A resting‐state functional MRI study , 2011, Human brain mapping.

[41]  B. Biswal,et al.  Functional connectivity of default mode network components: Correlation, anticorrelation, and causality , 2009, Human brain mapping.

[42]  K. Davis,et al.  Cognitive and default‐mode resting state networks: Do male and female brains “rest” differently? , 2010, Human brain mapping.

[43]  Yuan Zhou,et al.  Schizophrenic patients and their unaffected siblings share increased resting-state connectivity in the task-negative network but not its anticorrelated task-positive network. , 2012, Schizophrenia bulletin.

[44]  Mick Brammer,et al.  Sex-dependent age modulation of frontostriatal and temporo-parietal activation during cognitive control , 2009, NeuroImage.

[45]  A. Turken,et al.  The Neural Architecture of the Language Comprehension Network: Converging Evidence from Lesion and Connectivity Analyses , 2011, Front. Syst. Neurosci..

[46]  Xiaohua Chen,et al.  Sex differences in regional gray matter in healthy individuals aged 44–48 years: A voxel-based morphometric study , 2007, NeuroImage.

[47]  Paul J. Laurienti,et al.  An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets , 2003, NeuroImage.

[48]  G. Crucian,et al.  Sex Differences in Right Hemisphere Tasks , 1998, Brain and Cognition.

[49]  Moo K. Chung,et al.  Integrating VBM into the General Linear Model with voxelwise anatomical covariates , 2007, NeuroImage.

[50]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[51]  S. Rombouts,et al.  Reduced resting-state brain activity in the "default network" in normal aging. , 2008, Cerebral cortex.

[52]  J. J. Pekar,et al.  Sex differences in cerebral laterality of language and visuospatial processing , 2006, Brain and Language.

[53]  Alan C. Evans,et al.  Growing Together and Growing Apart: Regional and Sex Differences in the Lifespan Developmental Trajectories of Functional Homotopy , 2010, The Journal of Neuroscience.

[54]  B. Miller,et al.  Neurodegenerative Diseases Target Large-Scale Human Brain Networks , 2009, Neuron.

[55]  Eileen Luders,et al.  Why Sex Matters: Brain Size Independent Differences in Gray Matter Distributions between Men and Women , 2009, The Journal of Neuroscience.

[56]  T Adali,et al.  A weighted least‐squares algorithm for estimation and visualization of relative latencies in event‐related functional MRI , 2000, Magnetic resonance in medicine.

[57]  Nikos Makris,et al.  Sex differences in prefrontal cortical brain activity during fMRI of auditory verbal working memory. , 2005, Neuropsychology.

[58]  Peter Williamson,et al.  Are anticorrelated networks in the brain relevant to schizophrenia? , 2007, Schizophrenia bulletin.

[59]  A. Riecher-Rössler,et al.  Prospects for the classification of mental disorders in women , 2007, European psychiatry.

[60]  Rex E. Jung,et al.  A Baseline for the Multivariate Comparison of Resting-State Networks , 2011, Front. Syst. Neurosci..

[61]  S. Baron-Cohen Testing the extreme male brain (EMB) theory of autism: Let the data speak for themselves , 2005, Cognitive neuropsychiatry.

[62]  Christian C. Ruff,et al.  The influence of sex differences and individual task performance on brain activation during planning , 2005, NeuroImage.

[63]  D. Wegesin,et al.  A Neuropsychologic Profile of Homosexual and Heterosexual Men and Women , 1998, Archives of sexual behavior.

[64]  A. Damasio,et al.  Deciding Advantageously Before Knowing the Advantageous Strategy , 1997, Science.

[65]  Vinod Menon,et al.  Author ' s personal copy Gender differences in the functional and structural neuroanatomy of mathematical cognition , 2009 .

[66]  Karl J. Friston,et al.  Cerebral Asymmetry and the Effects of Sex and Handedness on Brain Structure: A Voxel-Based Morphometric Analysis of 465 Normal Adult Human Brains , 2001, NeuroImage.

[67]  Paul M. Thompson,et al.  Mapping cortical gray matter in the young adult brain: Effects of gender , 2005, NeuroImage.

[68]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[69]  Yong He,et al.  Hemisphere- and gender-related differences in small-world brain networks: A resting-state functional MRI study , 2011, NeuroImage.

[70]  Gereon R Fink,et al.  Gender differences in the functional neuroanatomy of emotional episodic autobiographical memory , 2005, Human brain mapping.

[71]  L. A. Flashman,et al.  Sex differences in semantic language processing: A functional MRI study , 2003, Brain and Language.

[72]  Alan H. Wilman,et al.  Males and females differ in brain activation during cognitive tasks , 2006, NeuroImage.

[73]  S. Golaszewski,et al.  Sex differences in brain activation pattern during a visuospatial cognitive task: a functional magnetic resonance imaging study in healthy volunteers , 2003, Neuroscience Letters.

[74]  A. Craig How do you feel? Interoception: the sense of the physiological condition of the body , 2002, Nature Reviews Neuroscience.

[75]  R. Bluhm,et al.  Default mode network connectivity: effects of age, sex, and analytic approach , 2008, Neuroreport.