title: Proton Chemical Shift Imaging of the Brain in Pediatric and Adult Developmental Stuttering.
abstract: OBJECTIVE
  Developmental stuttering is a neuropsychiatric condition of incompletely understood brain origin. Our recent functional magnetic resonance imaging study indicates a possible partial basis of stuttering in circuits enacting self-regulation of motor activity, attention, and emotion.
  
  
  OBJECTIVE
  To further characterize the neurophysiology of stuttering through in vivo assay of neurometabolites in suspect brain regions.
  
  
  METHODS
  Proton chemical shift imaging of the brain was performed in a case-control study of children and adults with and without stuttering. Recruitment, assessment, and magnetic resonance imaging were performed in an academic research setting.
  
  
  METHODS
  Ratios of N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NAA) to creatine (Cr) and choline compounds (Cho) to Cr in widespread cerebral cortical, white matter, and subcortical regions were analyzed using region of interest and data-driven voxel-based approaches.
  
  
  RESULTS
  Forty-seven children and adolescents aged 5 to 17 years (22 with stuttering and 25 without) and 47 adults aged 21 to 51 years (20 with stuttering and 27 without) were recruited between June 2008 and March 2013. The mean (SD) ages of those in the stuttering and control groups were 12.2 (4.2) years and 13.4 (3.2) years, respectively, for the pediatric cohort and 31.4 (7.5) years and 30.5 (9.9) years, respectively, for the adult cohort. Region of interest-based findings included lower group mean NAA:Cr ratio in stuttering than nonstuttering participants in the right inferior frontal cortex (-7.3%; P = .02), inferior frontal white matter (-11.4%; P < .001), and caudate (-10.6%; P = .04), while the Cho:Cr ratio was higher in the bilateral superior temporal cortex (left: +10.0%; P = .03 and right: +10.8%; P = .01), superior temporal white matter (left: +14.6%; P = .003 and right: +9.5%; P = .02), and thalamus (left: +11.6%; P = .002 and right: +11.1%; P = .001). False discovery rate-corrected voxel-based findings were highly consistent with region of interest findings. Additional voxel-based findings in the stuttering sample included higher NAA:Cr and Cho:Cr ratios (regression coefficient, 197.4-275; P < .001) in the posterior cingulate, lateral parietal, hippocampal, and parahippocampal cortices and amygdala, as well as lower NAA:Cr and Cho:Cr ratios (regression coefficient, 119.8-275; P < .001) in the superior frontal and frontal polar cortices. Affected regions comprised nodes of the Bohland speech-production (motor activity regulation), default-mode (attention regulation), and emotional-memory (emotion regulation) networks. Regional correlations were also observed between local metabolites and stuttering severity (r = 0.40-0.52; P = .001-.02).
  
  
  CONCLUSIONS
  This spectroscopy study of stuttering demonstrates brainwide neurometabolite alterations, including several regions implicated by other neuroimaging modalities. Prior ascription of a role in stuttering to inferior frontal and superior temporal gyri, caudate, and other structures is affirmed. Consistent with prior functional magnetic resonance imaging findings, these results further intimate neurometabolic aberrations in stuttering in brain circuits subserving self-regulation of speech production, attention, and emotion.
authors.affiliation: Division of Child and Adolescent Psychiatry, University of California-Los Angeles Semel Institute for Neuroscience, Los Angeles.
authors.forename: Joseph
authors.initials: J
authors.lastname: O'Neill
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York3MRI Unit, New York State Psychiatric Institute, New York.
authors.forename: Zhengchao
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Keck School of Medicine at the University of Southern California, Los Angeles5Institute for the Developing Mind, Children's Hospital Los Angeles, Los Angeles, California.
authors.forename: Ravi
authors.initials: R
authors.lastname: Bansal
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Psychiatry, Division of Child and Adolescent Psychiatry, New York, New York.
authors.forename: Iliyan
authors.initials: I
authors.lastname: Ivanov
authors.affiliation: Department of Psychiatry, Columbia University, New York, New York3MRI Unit, New York State Psychiatric Institute, New York.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Hao
authors.affiliation: Keck School of Medicine at the University of Southern California, Los Angeles7Division of Neurology, Children's Hospital Los Angeles, Los Angeles, California.
authors.forename: Jay
authors.initials: J
authors.lastname: Desai
authors.affiliation: Division of Child and Adolescent Psychiatry, University of California-Los Angeles Semel Institute for Neuroscience, Los Angeles.
authors.forename: Elena
authors.initials: E
authors.lastname: Pozzi
authors.affiliation: Keck School of Medicine at the University of Southern California, Los Angeles5Institute for the Developing Mind, Children's Hospital Los Angeles, Los Angeles, California.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Peterson
mesh_terms: D000293:Adolescent; D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002794:Choline / Q000378:metabolism; D015331:Cohort Studies; D003401:Creatine / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D066244:Proton Magnetic Resonance Spectroscopy; D012016:Reference Values; D013342:Stuttering / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D001224:Aspartic Acid; C000179:N-acetylaspartate; D003401:Creatine; D002794:Choline