Resting-state activity in development and maintenance of normal brain function

Carolyn E. Pizoli, Manish N. Shah, Abraham Z. Snyder, Joshua S. Shimony, David D. Limbrick, Marcus E. Raichle, Bradley L. Schlaggar, Matthew D. Smyth

Research output: Contribution to journalArticle

98 Scopus citations

Abstract

One of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level-dependent (BOLD) functional MRI signal. These BOLD fluctuations exhibit temporal synchrony within widely distributed brain regions known as resting-state networks. Resting-state networks are present in the waking state, during sleep, and under general anesthesia, suggesting that spontaneous neuronal activity plays a fundamental role in brain function. Despite its ubiquitous presence, the physiological role of correlated, spontaneous neuronal activity remains poorly understood. One hypothesis is that this activity is critical for the development of synaptic connections and maintenance of synaptic homeostasis. We had a unique opportunity to test this hypothesis in a 5-y-old boy with severe epileptic encephalopathy. The child developed marked neurologic dysfunction in association with a seizure disorder, resulting in a 1-y period of behavioral regression and progressive loss of developmental milestones. His EEG showed a markedly abnormal pattern of high-amplitude, disorganized slow activity with frequent generalized and multifocal epileptiform discharges. Resting-state functional connectivity MRI showed reduced BOLD fluctuations and a pervasive lack of normal connectivity. The child underwent successful corpus callosotomy surgery for treatment of drop seizures. Postoperatively, the patient's behavior returned to baseline, and he resumed development of new skills. The waking EEG revealed a normal background, and functional connectivity MRI demonstrated restoration of functional connectivity architecture. These results provide evidence that intrinsic, coherent neuronal signaling may be essential to the development and maintenance of the brain's functional organization.

Original languageEnglish
Pages (from-to)11638-11643
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number28
DOIs
StatePublished - Jul 12 2011

Keywords

  • Developmental neuroimaging
  • Epilepsy

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