title: Sleep reverts changes in human gray and white matter caused by wake-dependent training.
abstract: Learning leads to rapid microstructural changes in gray (GM) and white (WM) matter. Do these changes continue to accumulate if task training continues, and can they be reverted by sleep? We addressed these questions by combining structural and diffusion weighted MRI and high-density EEG in 16 subjects studied during the physiological sleep/wake cycle, after 12 h and 24 h of intense practice in two different tasks, and after post-training sleep. Compared to baseline wake, 12 h of training led to a decline in cortical mean diffusivity. The decrease became even more significant after 24 h of task practice combined with sleep deprivation. Prolonged practice also resulted in decreased ventricular volume and increased GM and WM subcortical volumes. All changes reverted after recovery sleep. Moreover, these structural alterations predicted cognitive performance at the individual level, suggesting that sleep's ability to counteract performance deficits is linked to its effects on the brain microstructure. The cellular mechanisms that account for the structural effects of sleep are unknown, but they may be linked to its role in promoting the production of cerebrospinal fluid and the decrease in synapse size and strength, as well as to its recently discovered ability to enhance the extracellular space and the clearance of brain metabolites.
authors.affiliation: Dept. of Psychiatry, University of Wisconsin, Madison, WI 53719, USA; Laboratory of Clinical Biochemistry and Molecular Biology, University of Pisa, Pisa 56126, Italy; Clinical Psychology Branch, University of Pisa, AOUP Santa Chiara, Pisa 56126, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Bernardi
authors.affiliation: Laboratory of Clinical Biochemistry and Molecular Biology, University of Pisa, Pisa 56126, Italy; Clinical Psychology Branch, University of Pisa, AOUP Santa Chiara, Pisa 56126, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cecchetti
authors.affiliation: Dept. of Psychiatry, University of Wisconsin, Madison, WI 53719, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Siclari
authors.affiliation: Dept. of Psychiatry, University of Wisconsin, Madison, WI 53719, USA.
authors.forename: Andreas
authors.initials: A
authors.lastname: Buchmann
authors.affiliation: Dept. of Psychiatry, University of Wisconsin, Madison, WI 53719, USA.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Yu
authors.affiliation: Laboratory of Clinical Biochemistry and Molecular Biology, University of Pisa, Pisa 56126, Italy; Clinical Psychology Branch, University of Pisa, AOUP Santa Chiara, Pisa 56126, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Handjaras
authors.affiliation: Dept. of Psychiatry, University of Wisconsin, Madison, WI 53719, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Bellesi
authors.affiliation: Laboratory of Clinical Biochemistry and Molecular Biology, University of Pisa, Pisa 56126, Italy; Clinical Psychology Branch, University of Pisa, AOUP Santa Chiara, Pisa 56126, Italy.
authors.forename: Emiliano
authors.initials: E
authors.lastname: Ricciardi
authors.affiliation: Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI 53705, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Kecskemeti
authors.affiliation: Dept. of Psychiatry, University of Wisconsin, Madison, WI 53719, USA.
authors.forename: Brady A
authors.initials: BA
authors.lastname: Riedner
authors.affiliation: Dept. of Psychiatry, University of Wisconsin, Madison, WI 53719, USA; Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin, Madison, WI 53705, USA; Dept. of Medical Physics, University of Wisconsin, Madison, WI 53705, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Alexander
authors.affiliation: Dept. of Psychiatry, University of Wisconsin, Madison, WI 53719, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Benca
authors.affiliation: Dept. of Physiology and Pharmacology, City University of New York Medical School, New York, NY 10031, USA.
authors.forename: M Felice
authors.initials: MF
authors.lastname: Ghilardi
authors.affiliation: Laboratory of Clinical Biochemistry and Molecular Biology, University of Pisa, Pisa 56126, Italy; Clinical Psychology Branch, University of Pisa, AOUP Santa Chiara, Pisa 56126, Italy; IMT School for Advanced Studies Lucca, Lucca 55100, Italy. Electronic address: pietro.pietrini@imtlucca.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Pietrini
authors.affiliation: Dept. of Psychiatry, University of Wisconsin, Madison, WI 53719, USA. Electronic address: ccirelli@wisc.edu.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cirelli
authors.affiliation: Dept. of Psychiatry, University of Wisconsin, Madison, WI 53719, USA. Electronic address: gtononi@wisc.edu.
authors.forename: Giulio
authors.initials: G
authors.lastname: Tononi
mesh_terms: D001921:Brain / Q000503:physiopathology*; D038524:Diffusion Magnetic Resonance Imaging; D004569:Electroencephalography; D005260:Female; D066128:Gray Matter / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007858:Learning / Q000502:physiology*; D008297:Male; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology*; D014851:Wakefulness; D066127:White Matter / Q000503:physiopathology; D055815:Young Adult
keywords: DWI; Extracellular space; MRI; Mean diffusivity; Sleep deprivation
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