GABA, Resting-State Connectivity and the Developing Brain

Kwon, Soo Hyun; Mayes, Linda C.; Lacadie, Cheryl; Benjamin, Jennifer; Myers, Eliza; Qiu, Maolin; Schneider, Karen; Rothman, Douglas L.; Constable, R. Todd; Ment, Laura R.

doi:10.1159/000362433

Cited by 58 publications

(68 citation statements)

References 30 publications

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“…The majority of GABA is located in two pools within neurons - the cytoplasm and the presynaptic vesicles (Kwon et al, 2014). However, MRS is only capable of detecting total GABA within the prescribed localized region, and it cannot distinguish between these separate functional pools of GABA (Stagg et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Decreased auditory GABA+ concentrations in presbycusis demonstrated by edited magnetic resonance spectroscopy

Gao

Wang

et al. 2015

NeuroImage

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Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central auditory system. Altered GABAergic neurotransmission has been found in both the inferior colliculus and the auditory cortex in animal models of presbycusis. Edited magnetic resonance spectroscopy (MRS), using the MEGA-PRESS sequence, is the most widely used technique for detecting GABA in the human brain. However, to date there has been a paucity of studies exploring changes to the GABA concentrations in the auditory region of patients with presbycusis. In this study, sixteen patients with presbycusis (5 males/11 females, mean age 63.1 ± 2.6 years) and twenty healthy controls (6 males/14 females, mean age 62.5 ± 2.3 years) underwent audiological and MRS examinations. Pure tone audiometry from 0.125 to 8 KHz and tympanometry were used to assess the hearing abilities of all subjects. The pure tone average (PTA; the average of hearing thresholds at 0.5, 1, 2, and 4 kHz) was calculated. The MEGA-PRESS sequence was used to measure GABA+ concentrations in 4 × 3 × 3 cm3 volumes centered on the left and right Heschl’s gyri. GABA+ concentrations were significantly lower in the presbycusis group compared to the control group (left auditory regions: p = 0.002, right auditory regions: p = 0.008). Significant negative correlations were observed between PTA and GABA+ concentrations in the presbycusis group (r = −0.57, p = 0.02), while a similar trend was found in the control group (r = −0.40, p = 0.08). These results are consistent with a hypothesis of dysfunctional GABAergic neurotransmission in the central auditory system in presbycusis, and suggest a potential treatment target for presbycusis.

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Section: Discussionmentioning

confidence: 99%

Decreased auditory GABA+ concentrations in presbycusis demonstrated by edited magnetic resonance spectroscopy

Gao

Wang

et al. 2015

NeuroImage

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“…Data analyses were performed as previously described (Kwon et al, 2014). Briefly, data were converted from Digital Imaging and Communication in Medicine format to analyze format using XMedCon (http://xmedcon.sourceforge.net/).…”

Section: Methodsmentioning

confidence: 99%

Adaptive mechanisms of developing brain: Cerebral lateralization in the prematurely-born

et al. 2015

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Preterm birth results in alterations in neural connectivity, but the impact of prematurity on the functional organization of the developing brain has yet to be explored. To test the hypothesis that preterm birth alters cortical organization during the late second and third trimesters of gestation, we interrogated cerebral lateralization at rest in 26 very preterm subjects (birth weight 500–1500 g) with no evidence of brain injury and 25 healthy term control subjects at term equivalent age. Employing an unbiased voxel-based measure of functional connectivity, these data demonstrated that cerebral lateralization is impaired in the prematurely-born. At term equivalent age, preterm neonates showed significantly less lateralization in regions subserving both receptive and expressive language, left Brodmann (BA) areas insula-BA22-BA21 and L BA45-BA47 (p<0.05 corrected for multiple comparisons for both). Exploratory region of interest analyses demonstrated significantly less inter-hemispheric connectivity from L BA22 to R BA22 in preterm infants compared to term controls (p<0.005) and from R BA22 to its homolog (p<0.005). L BA22, Wernicke’s area, was more strongly connected to R BA39, foreshadowing neural networks for language in preterm subjects at school age, adolescence and young adulthood. For these very preterm neonates born at less than 30 weeks PMA, the degree of prematurity had no influence on lateralization in these differential regions.

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“…Data analyses were performed as previously described (Kwon et al 2014a). Briefly, images were slice-time-corrected and motion-corrected using SPM5 (http://www.fil.ion.ucl.ac.uk/spm/software/spm5/).…”

Section: Methodsmentioning

confidence: 99%

Preterm birth alters neonatal, functional rich club organization

et al. 2015

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Alterations in neural networks are associated with the cognitive difficulties of the prematurely born. Using functional magnetic resonance imaging, we analyzed functional connectivity for preterm (PT) and term neonates at term equivalent age. Specifically, we constructed whole-brain networks and examined rich club (RC) organization, a common construct among complex systems where important (or “rich”) nodes connect preferentially to other important nodes. Both, PT and term neonates showed RC organization with PT neonates exhibiting significantly reduced connections between these RC nodes. Additionally, PT neonates showed evidence of weaker functional segregation. Our results suggest that PT birth is associated with fundamental changes of functional organization in the developing brain.

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GABA, Resting-State Connectivity and the Developing Brain

Cited by 58 publications

References 30 publications

Decreased auditory GABA+ concentrations in presbycusis demonstrated by edited magnetic resonance spectroscopy

Decreased auditory GABA+ concentrations in presbycusis demonstrated by edited magnetic resonance spectroscopy

Adaptive mechanisms of developing brain: Cerebral lateralization in the prematurely-born

Preterm birth alters neonatal, functional rich club organization

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