Broadband neurophysiological abnormalities in the medial prefrontal region of the default‐mode network in adults with ADHD

Previous investigations of the default‐mode network (DMN) in persons with attention‐deficit/hyperactivity disorder (ADHD) have shown reduced functional connectivity between the anterior and posterior aspects. This finding was originally demonstrated in adults with ADHD, then in youth with ADHD, and has been tentatively linked to ultra low frequency oscillations within the DMN. The current study evaluates the specificity of DMN abnormalities to neuronal oscillations in the ultra low frequency range, and examines the regional specificity of these DMN aberrations in medicated and unmedicated adults with, and those without ADHD. An individually matched sample of adults with and without ADHD completed 6‐minute sessions of resting‐state magnetoencephalography (MEG). Participants with ADHD were known responders to stimulant medications and completed two sessions (predrug/postdrug). MEG data were coregistered to the participant's MRI, corrected for head motion, fitted to a regional‐level source model, and subjected to spectral analyses to extract neuronal population activity in regions of the DMN. The unmedicated adults with ADHD exhibited broadband deficits in medial prefrontal cortices (MPFC), but not other DMN regions compared to adults without ADHD. Unmedicated patients also showed abnormal cross‐frequency coupling in the gamma range between the MPFC and posterior cingulate areas, and disturbed balance within the DMN as activity in posterior regions was stronger than frontal regions at beta and lower frequencies, which dissipated at higher γ‐frequencies. Administration of pharmacotherapy significantly increased prefrontal alpha activity (8–14 Hz) in adults with ADHD, and decreased the cross‐frequency gamma coupling. These results indicate that neurophysiological aberrations in the DMN of patients with ADHD are not limited to ultra slow oscillations, and that they may be primarily attributable to abnormal broadband activity in the MPFC. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.

[1]  H. Hotelling.  New Light on the Correlation Coefficient and its Transforms , 1953 .

[2]  Kerstin Konrad,et al.  Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder , 2010, Human brain mapping.

[3]  Alan C. Evans,et al.  Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation , 2007, Proceedings of the National Academy of Sciences.

[4]  G. Fink,et al.  Minds at rest? Social cognition as the default mode of cognizing and its putative relationship to the “default system” of the brain , 2008, Consciousness and Cognition.

[5]  R. Fisher.  014: On the "Probable Error" of a Coefficient of Correlation Deduced from a Small Sample. , 1921 .

[6]  S. Taulu,et al.  Applications of the signal space separation method , 2005, IEEE Transactions on Signal Processing.

[7]  Jonathan D. Power,et al.  The Development of Human Functional Brain Networks , 2010, Neuron.

[8]  L. Seidman,et al.  Neuropsychological function in adults with attention-deficit/hyperactivity disorder. , 2004, The Psychiatric clinics of North America.

[9]  Simon B Eickhoff,et al.  Investigating the Functional Heterogeneity of the Default Mode Network Using Coordinate-Based Meta-Analytic Modeling , 2009, The Journal of Neuroscience.

[10]  R. Fisher.  FREQUENCY DISTRIBUTION OF THE VALUES OF THE CORRELATION COEFFIENTS IN SAMPLES FROM AN INDEFINITELY LARGE POPU;ATION , 1915 .

[11]  Patrick Berg,et al.  Advanced Tools for Digital EEG Review:: Virtual Source Montages, Whole-head Mapping, Correlation, and Phase Analysis , 2002, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[12]  Karsten Hoechstetter,et al.  BESA Source Coherence: A New Method to Study Cortical Oscillatory Coupling , 2003, Brain Topography.

[13]  A. Karl,et al.  Altered spontaneous low frequency brain activity in Attention Deficit/Hyperactivity Disorder , 2010, Brain Research.

[14]  In English,et al.  The Numbers Count: Mental Disorders in America , 2013 .

[15]  Joseph Biederman,et al.  Presenting ADHD symptoms, subtypes, and comorbid disorders in clinically referred adults with ADHD. , 2009, The Journal of clinical psychiatry.

[16]  S. Debener,et al.  Very low frequency EEG oscillations and the resting brain in young adults: a preliminary study of localisation, stability and association with symptoms of inattention , 2007, Journal of Neural Transmission.

[17]  G. Mangun,et al.  Functional Disconnection of Frontal Cortex and Visual Cortex in Attention-Deficit/Hyperactivity Disorder , 2010, Biological Psychiatry.

[18]  S. Petersen,et al.  The maturing architecture of the brain's default network , 2008, Proceedings of the National Academy of Sciences.

[19]  S. Faraone,et al.  Neuropsychological function in adults with attention-deficit hyperactivity disorder , 1998, Biological Psychiatry.

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

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

[22]  W. Singer,et al.  Frontiers in Integrative Neuroscience Integrative Neuroscience Neural Synchrony in Cortical Networks: History, Concept and Current Status , 2022 .

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

[24]  Hongtu Zhu,et al.  An FMRI study of the effects of psychostimulants on default-mode processing during Stroop task performance in youths with ADHD. , 2009, The American journal of psychiatry.

[25]  Joseph Biederman,et al.  The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies , 2005, Psychological Medicine.

[26]  S. Taulu,et al.  Spatiotemporal signal space separation method for rejecting nearby interference in MEG measurements , 2006, Physics in medicine and biology.

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

[28]  Alan C. Evans,et al.  Cortical development in typically developing children with symptoms of hyperactivity and impulsivity: support for a dimensional view of attention deficit hyperactivity disorder. , 2011, The American journal of psychiatry.

[29]  Deepti R. Bathula,et al.  Atypical Default Network Connectivity in Youth with Attention-Deficit/Hyperactivity Disorder , 2010, Biological Psychiatry.

[30]  Mental health in the United States. Prevalence of diagnosis and medication treatment for attention-deficit/hyperactivity disorder--United States, 2003. , 2005, MMWR. Morbidity and mortality weekly report.

[31]  R. Kessler,et al.  The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. , 2006, The American journal of psychiatry.

[32]  Jonathan D. Power,et al.  Functional Brain Networks Develop from a “Local to Distributed” Organization , 2009, PLoS Comput. Biol..

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

[34]  W. Singer,et al.  The gamma cycle , 2007, Trends in Neurosciences.

[35]  K D Singh,et al.  Transient and linearly graded deactivation of the human default-mode network by a visual detection task , 2008, NeuroImage.

[36]  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.

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

[38]  R. Oostenveld,et al.  Neuronal Dynamics Underlying High- and Low-Frequency EEG Oscillations Contribute Independently to the Human BOLD Signal , 2011, Neuron.

[39]  Rozmin Halari,et al.  Methylphenidate normalises activation and functional connectivity deficits in attention and motivation networks in medication-naïve children with ADHD during a rewarded continuous performance task , 2009, Neuropharmacology.

[40]  Olga V. Demler,et al.  The World Health Organization adult ADHD self-report scale (ASRS): a short screening scale for use in the general population , 2005, Psychological Medicine.

[41]  Wolf Singer,et al.  Neuronal Synchrony: A Versatile Code for the Definition of Relations? , 1999, Neuron.