The DOI matches its Crossref record; 67 of the 68 references it cites were found in a registry or an index.
GABA estimation in the brains of children on the autism spectrum: Measurement precision and regional cortical variation
Open accessAbstract
(1)H magnetic resonance spectroscopy ((1)H MRS) and spectral editing methods, such as MEGA-PRESS, allow researchers to investigate metabolite and neurotransmitter concentrations in-vivo. Here we address the utilization of (1)H MRS for the investigation of GABA concentrations in the ASD brain, in three locations; motor, visual and auditory areas. An initial repeatability study (5 subjects, 5 repeated measures separated by ~5days on average) indicated no significant effect of reference metabolite choice on GABA quantitation (p>0.6). Coefficients of variation for GABA+/NAA, GABA+/Cr and GABA+/Glx were all of the order of 9-11%. Based on these findings, we investigated creatine-normalized GABA+ ratios (GABA+/Cr) in a group of (N=17) children with autism spectrum disorder (ASD) and (N=17) typically developing children (TD) for Motor, Auditory and Visual regions of interest (ROIs). Linear regression analysis of gray matter (GM) volume changes (known to occur with development) revealed a significant decrease of GM volume with Age for Motor (F(1,30)=17.92; p<0.001) and Visual F(1,16)=14.41; p<0.005 but not the Auditory ROI (p=0.55). Inspection of GABA+/Cr changes with Age revealed a marginally significant change for the Motor ROI only (F(1,30)=4.11; p=0.054). Subsequent analyses were thus conducted for each ROI separately using Age and GM volume as covariates. No group differences in GABA+/Cr were observed for the Visual ROI between TD vs. ASD children. However, the Motor and Auditory ROI showed significantly reduced GABA+/Cr in ASD (Motor p<0.05; Auditory p<0.01). The mean deficiency in GABA+/Cr from the Motor ROI was approximately 11% and Auditory ROI was approximately 22%. Our novel findings support the model of regional differences in GABA+/Cr in the ASD brain, primarily in Auditory and to a lesser extent Motor but not Visual areas.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“These MRS studies in children with ASD have found reduced GABA (the major inhibitory neurotransmitter) levels in auditory and motor cortex (Gaetz et al., 2014)”
From Behavioral, Perceptual, and Neural Alterations in Sensory and Multisensory Function in Autism Spectrum Disorder (2015) · cites this paper as Gaetz et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Lord, C., Rutter, M., & Le Couteur, A. (1994) · Journal of Autism and Developmental Disorders · doi:10.1007/bf02172145 · Cited by 9,065
Zhang, Y., Brady, M., & Smith, S. M. (2001) · IEEE Transactions on Medical Imaging · doi:10.1109/42.906424 · Cited by 7,628
Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., Pickles, A., & Rutter, M. (2000) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1005592401947 · Cited by 7,520
A global optimisation method for robust affine registration of brain images
Jenkinson, M., & Smith, S. M. (2001) · Medical Image Analysis · doi:10.1016/s1361-8415(01)00036-6 · Cited by 6,983
A mechanism for cognitive dynamics: neuronal communication through neuronal coherence.
Fries, P. (2005) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2005.08.011 · Cited by 4,284
Model of autism: increased ratio of excitation/inhibition in key neural systems
Rubenstein, J. L. R., & Merzenich, M. M. (2003) · Genes, Brain and Behavior · doi:10.1034/j.1601-183x.2003.00037.x · Cited by 2,768
Mazziotta, J. C., Toga, A. W., Evans, A. C., Fox, P. T., Lancaster, J. L., Zilles, K., Woods, R. P., Paus, T., Simpson, G. V., Pike, G. B., et al. (2001) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2001.0915 · Cited by 2,417
Oscillatory gamma activity in humans and its role in object representation
Tallon‐Baudry, C. (1999) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(99)01299-1 · Cited by 2,205
Localization of the motor hand area to a knob on the precentral gyrus. A new landmark
Yousry, T. A. (1997) · Brain · doi:10.1093/brain/120.1.141 · Cited by 1,840
Neuronal gamma-band synchronization as a fundamental process in cortical computation
Fries, P. (2009) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.051508.135603 · Cited by 1,713
Dapretto, M., Davies, M. S., Pfeifer, J. H., Scott, A. A., Sigman, M., Bookheimer, S. Y., & Iacoboni, M. (2006) · Nature Neuroscience · doi:10.1038/nn1611 · Cited by 1,694
Improved Method for Accurate and Efficient Quantification of MRS Data with Use of Prior Knowledge
Vanhamme, L., van den Boogaart, A., & Huffel, S. V. (1997) · Journal of Magnetic Resonance · doi:10.1006/jmre.1997.1244 · Cited by 1,631
Evidence of Brain Overgrowth in the First Year of Life in Autism
Courchesne, E. (2003) · JAMA · doi:10.1001/jama.290.3.337 · Cited by 1,120
Fries, P., Nikolić, D., & Singer, W. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.05.005 · Cited by 1,044
Java-based graphical user interface for the MRUI quantitation package
Naressi, A., Couturier, C., Devos, J. M., Janssen, M., Mangeat, C., de Beer, R., & Graveron‐Demilly, D. (2001) · Magnetic Resonance Materials in Physics Biology and Medicine · doi:10.1007/bf02668096 · Cited by 1,003
Proton nuclear magnetic resonance spectroscopy unambiguously identifies different neural cell types
Urenjak, J., Williams, S. R., Gadian, D. G., & Noble, M. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-03-00981.1993 · Cited by 995
Constantino, J. N. (2013) · Encyclopedia of Autism Spectrum Disorders · doi:10.1007/978-1-4419-1698-3_296 · Cited by 908
Glutamine and glutamate—their central role in cell metabolism and function
Newsholme, P., Procópio, J., Lima, M. M. R., Pithon‐Curi, T. C., & Curi, R. (2002) · Cell Biochemistry and Function · doi:10.1002/cbf.1003 · Cited by 706
When Is the Brain Enlarged in Autism? A Meta-Analysis of All Brain Size Reports
Redcay, E., & Courchesne, E. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.03.026 · Cited by 604
Localization of the motor hand area to a knob on the precentral gyrus.
Yousry, T. A. (1997) · Medical Entomology and Zoology · Cited by 594
Abnormal cortical voice processing in autism
Gervais, H., Belin, P., Boddaert, N., Leboyer, M., Coez, A., Sfaello, I., Barthélémy, C., Brunelle, F., Samson, Y., & Zilbovicius, M. (2004) · Nature Neuroscience · doi:10.1038/nn1291 · Cited by 568
Muthukumaraswamy, S. D., Edden, R. A. E., Jones, D. K., Swettenham, J. B., & Singh, K. D. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900728106 · Cited by 562
Urenjak, J., Williams, S. R., Gadian, D. G., & Noble, M. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb08875.x · Cited by 503
Hazlett, H. C., Poe, M. D., Gerig, G., Styner, M., Chappell, C., Smith, R. G., Vachet, C., & Piven, J. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.39 · Cited by 481
Magnetic resonance spectroscopy of the brain: review of metabolites and clinical applications
Soares, D., & Law, M. (2008) · Clinical Radiology · doi:10.1016/j.crad.2008.07.002 · Cited by 461
Motor Abilities in Autism: A Review Using a Computational Context
Gowen, E., & Hamilton, A. F. D. C. (2012) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-012-1574-0 · Cited by 450
Yoon, J. H., Maddock, R. J., Rokem, A., Silver, M. A., Minzenberg, M. J., Ragland, J. D., & Carter, C. S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.6158-09.2010 · Cited by 408
1H MR Spectroscopy of the Brain: Absolute Quantification of Metabolites
Jansen, J. F. A., Backes, W. H., Nicolay, K., & Kooi, M. E. (2006) · Radiology · doi:10.1148/radiol.2402050314 · Cited by 405
In vivo magnetic resonance spectroscopy of GABA: A methodological review
Puts, N. A. J., & Edden, R. A. E. (2011) · Progress in Nuclear Magnetic Resonance Spectroscopy · doi:10.1016/j.pnmrs.2011.06.001 · Cited by 394
Neural correlates of executive function in Autistic Spectrum Disorders
Schmitz, N., Rubia, K., Daly, E., Smith, A., Williams, S., & Murphy, D. G. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.06.007 · Cited by 365
Autism and Asperger syndrome: coexistence with other clinical disorders
Gillberg and, C., & Billstedt, E. (2000) · Acta Psychiatrica Scandinavica · doi:10.1034/j.1600-0447.2000.102005321.x · Cited by 352
Purkinje Cell Size Is Reduced in Cerebellum of Patients with Autism
Fatemi, S. H., Halt, A. R., Realmuto, G., Earle, J., Kist, D. A., Thuras, P., & Merz, A. (2002) · Cellular and Molecular Neurobiology · doi:10.1023/a:1019861721160 · Cited by 344
Alterations of GABAergic Signaling in Autism Spectrum Disorders
Pizzarelli, R., & Cherubini, E. (2011) · Neural Plasticity · doi:10.1155/2011/297153 · Cited by 338
Validating γ oscillations and delayed auditory responses as translational biomarkers of autism
Gandal, M. J., Edgar, J. C., Ehrlichman, R. S., Mehta, M., Roberts, T. P. L., & Siegel, S. J. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.031 · Cited by 314
Self-citationGaetz, W. C., Edgar, J. C., Wang, D.-J., & Roberts, T. P. L. (2011) · NeuroImage · doi:10.1016/j.neuroimage.2010.12.077 · Cited by 308
Self-citationDecreased GAD67 mRNA levels in cerebellar Purkinje cells in autism: pathophysiological implications
Yip, J., Soghomonian, J.-J., & Blatt, G. J. (2007) · Acta Neuropathologica · doi:10.1007/s00401-006-0176-3 · Cited by 303
Oscillatory gamma activity in humans: a possible role for object representation
Bertrand, O., & Tallon‐Baudry, C. (2000) · International Journal of Psychophysiology · doi:10.1016/s0167-8760(00)00166-5 · Cited by 299
Roberts, T. P. L., Khan, S. Y., Rey, M., Monroe, J. F., Cannon, K. M., Blaskey, L. G., Woldoff, S., Qasmieh, S., Gandal, M., Schmidt, G. L., et al. (2010) · Autism Research · doi:10.1002/aur.111 · Cited by 295
Self-citationHigh-resolution 1H nuclear magnetic resonance study of cerebral hypoxia in vivo.
Behar, K. L., den Hollander, J. A., Stromski, M. E., Ogino, T., Shulman, R. G., Petroff, O. A. C., & Prichard, J. W. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.16.4945 · Cited by 292
TALLON-BAUDRY, C., KREITER, A., & BERTRAND, O. (1999) · Visual Neuroscience · doi:10.1017/s0952523899163065 · Cited by 281
Harada, M., Taki, M. M., Nose, A., Kubo, H., Mori, K., Nishitani, H., & Matsuda, T. (2011) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-010-1065-0 · Cited by 231
Expression of GABAB Receptors Is Altered in Brains of Subjects with Autism
Fatemi, S. H., Folsom, T. D., Reutiman, T. J., & Thuras, P. D. (2009) · The Cerebellum · doi:10.1007/s12311-008-0075-3 · Cited by 227
In vivo detection of GABA and glutamate with MEGA‐PRESS: Reproducibility and gender effects
Tuura, R., Michels, L., Edden, R. A. E., Murdoch, J. B., & Martin, E. (2011) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.22520 · Cited by 219
Decreased GABA B receptors in the cingulate cortex and fusiform gyrus in Autism
Oblak, A. L., Gibbs, T. T., & Blatt, G. J. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06858.x · Cited by 203
Groenendaal, F., Veenhoven, R. H., van der Grond, J., Jansen, G. H., Witkamp, T. D., & de Vries, L. S. (1994) · Pediatric Research · doi:10.1203/00006450-199402000-00004 · Cited by 198
Decreased left perisylvian GABA concentration in children with autism and unaffected siblings
Rojas, D. C., Singel, D., Steinmetz, S. E., Hepburn, S., & Brown, M. S. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.01.045 · Cited by 197
COURCHESNE, E., REDCAY, E., MORGAN, J. T., & KENNEDY, D. P. (2005) · Development and Psychopathology · doi:10.1017/s0954579405050285 · Cited by 192
Regionally Specific Human GABA Concentration Correlates with Tactile Discrimination Thresholds
Puts, N. A. J., Edden, R. A. E., Evans, J., McGlone, F. P., & McGonigle, D. J. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4489-11.2011 · Cited by 177
Page, L., Daly, E., Schmitz, N., Simmons, A., Toal, F., Deeley, Q., Ambery, F., McAlonan, G. M., Murphy, K. C., & Murphy, D. G. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.12.2189 · Cited by 177
Oblak, A. L., Gibbs, T. T., & Blatt, G. J. (2010) · Brain Research · doi:10.1016/j.brainres.2010.09.021 · Cited by 175
Baseline GABA concentration and fMRI response
Donahue, M. J., Near, J., Blicher, J. U., & Jezzard, P. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.07.017 · Cited by 174
Auditory Magnetic Mismatch Field Latency: A Biomarker for Language Impairment in Autism
Roberts, T. P. L., Cannon, K. M., Tavabi, K., Blaskey, L. G., Khan, S. Y., Monroe, J. F., Qasmieh, S., Levy, S. E., & Edgar, J. C. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.01.015 · Cited by 171
Self-citationInvestigation of autism and GABA receptor subunit genes in multiple ethnic groups
Collins, A. L., Ma, D., Whitehead, P. L., Martin, E. R., Wright, H. H., Abramson, R. K., Hussman, J. P., Haines, J. L., Cuccaro, M. L., Gilbert, J. R., et al. (2006) · Neurogenetics · doi:10.1007/s10048-006-0045-1 · Cited by 169
Correlation between EEG abnormalities and symptoms of autism spectrum disorder (ASD)
Yasuhara, A. (2010) · Brain and Development · doi:10.1016/j.braindev.2010.08.010 · Cited by 162
NMR Spectroscopy of Brain Metabolism In Vivo
Prichard, J. W., & Shulman, R. G. (1986) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.09.030186.000425 · Cited by 132
Clinical and anatomical heterogeneity in autistic spectrum disorder: a structural MRI study
Toal, F., Daly, E. M., Page, L., Deeley, Q., Hallahan, B., Bloemen, O., Cutter, W. J., Brammer, M. J., Curran, S., Robertson, D., et al. (2010) · Psychological Medicine · doi:10.1017/s0033291709991541 · Cited by 121
Bottomley, P. A., Edelstein, W. A., Foster, T. H., & Adams, W. A. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.7.2148 · Cited by 115
Proton magnetic resonance spectroscopic imaging of the brain in childhood autism
Levitt, J. G., O’Neill, J., Blanton, R. E., Smalley, S. L., Fadale, D., McCracken, J. T., Guthrie, D., Toga, A. W., & Alger, J. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00688-7 · Cited by 103
Harada, M., Kubo, H., Nose, A., Nishitani, H., & Matsuda, T. (2010) · Human Brain Mapping · doi:10.1002/hbm.21086 · Cited by 92
Aoki, Y. Y., Kasai, K., & Yamasue, H. (2012) · Translational Psychiatry · doi:10.1038/tp.2011.65 · Cited by 85
Punwani, S., Ordidge, R. J., Cooper, C. E., Amess, P., & Clemence, M. (1998) · NMR in Biomedicine · doi:10.1002/(sici)1099-1492(199810)11:6 · Cited by 74
Aufhaus, E., Weber‐Fahr, W., Sack, M., Tunc‐Skarka, N., Oberthuer, G., Hoerst, M., Meyer‐Lindenberg, A., Boettcher, U., & Ende, G. (2012) · Magnetic Resonance in Medicine · doi:10.1002/mrm.24257 · Cited by 73
Reproducibility of prefrontal γ‐aminobutyric acid measurements with J‐edited spectroscopy
Geramita, M. A., van der Veen, J. W. C., Barnett, A. S., Farmer, A. S., Shen, J., Weinberger, D. R., & Marenco, S. (2011) · NMR in Biomedicine · doi:10.1002/nbm.1662 · Cited by 72
Neurometabolic effects of an inborn error of amino acid metabolism demonstrated in vivo by 1H NMR
Gadian, D. G., Proctor, E., Williams, S. R., Cady, E. B., & Gardiner, R. M. (1986) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910030123 · Cited by 64
Legget, K. T., Hepburn, S., Winterrowd, E. M., Schmidt, G. L., & Rojas, D. C. (2012) · BMC Psychiatry · doi:10.1186/1471-244x-12-213 · Cited by 56
Measurement of GABA and contaminants in gray and white matter in human brain in vivo
Choi, C., Bhardwaj, P. P., Kalra, S., Casault, C. A., Yasmin, U. S., Allen, P. S., & Coupland, N. J. (2007) · Magnetic Resonance in Medicine · doi:10.1002/mrm.21275 · Cited by 35
[In vivo magnetic resonance spectroscopy].
Bakken, I. J., Skjetne, T., Gribbestad, I. S., & Kvistad, K. A. (2002) · PubMed · Cited by 30
Cited by
Sorted by citations
Edden, R. A. E., Puts, N. A. J., Harris, A. D., Barker, P. B., & Evans, J. (2013) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.24478 · Cited by 625
Baum, S. H., Stevenson, R. A., & Wallace, M. T. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.09.007 · Cited by 370
Schür, R. R., Draisma, L. W. R., Wijnen, J. P., Boks, M. P., Koevoets, M., Joëls, M., Klomp, D. W. J., Kahn, R. S., & Vinkers, C. H. (2016) · Human Brain Mapping · doi:10.1002/hbm.23244 · Cited by 372
Cerliani, L., Mennes, M., Thomas, R. M., Di Martino, A., Thioux, M., & Keysers, C. (2015) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2015.0101 · Cited by 339
Reduced GABAergic Action in the Autistic Brain
Robertson, C. E., Ratai, E.-M., & Kanwisher, N. (2016) · Current Biology · doi:10.1016/j.cub.2015.11.019 · Cited by 327
Metadata
- Authors
- Gaetz, W., Bloy, L., Wang, D. J., Port, R. G., Blaskey, L., Levy, S. E., & Roberts, T. P. L.
- Affiliations
- Children's Hospital of Philadelphia (US)
- Corresponding author
- Gaetz, W.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 86
- Pages
- 1-9
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3883951
- OpenAlex
- W1973419361
- Cited by
- 267
- References
- 68
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 19 · 2023: 23 · 2022: 16 · 2021: 25 · 2020: 23 · 2019: 23 · 2018: 17 · 2017: 27 · 2016: 32 · 2015: 21 · 2014: 15
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01DC008871, P30HD026979)
- Nancy Lurie Marks Family Foundation (NLMFF)
- Pennsylvania Department of Health
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- GABA, autism spectrum disorder, children, motor cortex, auditory cortex, visual cortex, gray matter volume, age-related development, measurement precision, MEGA-PRESS, 1H magnetic resonance spectroscopy
- MeSH terms
- Adult, Cerebral Cortex, Child, Child Development Disorders, Pervasive, Female, gamma-Aminobutyric Acid, Humans, Magnetic Resonance Imaging, Male, Magnetic Resonance Spectroscopy, Sensitivity and Specificity, Tissue Distribution, Reproducibility of Results, Neurotransmitter Agents
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
