| dc.creator | Papadelis, Christos | |
| dc.creator | Ntolkeras, Georgios | |
| dc.creator | Latzer, Itay Tokatly | |
| dc.creator | DiBacco, Melissa L. | |
| dc.creator | Afacan, Onur | |
| dc.creator | Warfield, Simon | |
| dc.creator | Shi, Xutong | |
| dc.creator | Roullet, Jean-Baptiste | |
| dc.creator | Gibson, K. Michael | |
| dc.creator | Pearl, Phillip L. | |
| dc.date.accessioned | 2024-09-25T21:35:58Z | |
| dc.date.available | 2024-09-25T21:35:58Z | |
| dc.date.issued | 1/1/2023 | |
| dc.identifier.uri | https://doi.org/10.1093/braincomms/fcad291 | |
| dc.identifier.uri | https://repository.tcu.edu/handle/116099117/65987 | |
| dc.description | Succinic semialdehyde dehydrogenase deficiency is a rare autosomal recessively inherited metabolic disorder of gamma-aminobutyric acid catabolism manifested by intellectual disability, expressive aphasia, movement disorders, psychiatric ailments and epilepsy. Subjects with succinic semialdehyde dehydrogenase deficiency are characterized by elevated gamma-aminobutyric acid and related metabolites, such as gamma-guanidinobutyric acid, and an age-dependent downregulation of cerebral gamma-aminobutyric acid receptors. These findings indicate impaired gamma-aminobutyric acid and gamma-aminobutyric acid sub-type A (GABA(A)) receptor signalling as major factors underlying the pathophysiology of this neurometabolic disorder. We studied the cortical oscillation patterns and their relationship with gamma-aminobutyric acid metabolism in 18 children affected by this condition and 10 healthy controls. Using high-density EEG, we recorded somatosensory cortical responses and resting-state activity. Using electrical source imaging, we estimated the relative power changes (compared with baseline) in both stimulus-evoked and stimulus-induced responses for physiologically relevant frequency bands and resting-state power. Stimulus-evoked oscillations are phase locked to the stimulus, whereas induced oscillations are not. Power changes for both evoked and induced responses as well as resting-state power were correlated with plasma gamma-aminobutyric acid and gamma-guanidinobutyric acid concentrations and with cortical gamma-aminobutyric acid measured by proton magnetic resonance spectroscopy. Plasma gamma-aminobutyric acid, gamma-guanidinobutyric acid and cortical gamma-aminobutyric acid were higher in patients than in controls (P < 0.001 for both). Beta and gamma relative power were suppressed for evoked responses in patients versus controls (P < 0.01). No group differences were observed for induced activity (P > 0.05). The mean gamma frequency of evoked responses was lower in patients versus controls (P = 0.002). Resting-state activity was suppressed in patients for theta (P = 0.011) and gamma (P < 0.001) bands. Evoked power changes were inversely correlated with plasma gamma-aminobutyric acid and with gamma-guanidinobutyric acid for beta (P < 0.001) and gamma (P < 0.001) bands. Similar relationships were observed between the evoked power changes and cortical gamma-aminobutyric acid for all tested areas in the beta band (P < 0.001) and for the posterior cingulate gyrus in the gamma band (P < 0.001). We also observed a negative correlation between resting-state activity and plasma gamma-aminobutyric acid and gamma-guanidinobutyric acid for theta (P < 0.001; P = 0.003), alpha (P = 0.003; P = 0.02) and gamma (P = 0.02; P = 0.01) bands. Our findings indicate that increased gamma-aminobutyric acid concentration is associated with reduced sensory-evoked beta and gamma activity and impaired neuronal synchronization in patients with succinic semialdehyde dehydrogenase deficiency. This further elucidates the pathophysiology of this neurometabolic disorder and serves as a potential biomarker for therapeutic trials. | |
| dc.language | en | |
| dc.publisher | Oxford University Press (OUP) | |
| dc.source | BRAIN COMMUNICATIONS | |
| dc.title | Reduced evoked cortical beta and gamma activity and neuronal synchronization in succinic semialdehyde dehydrogenase deficiency, a disorder of ¿-aminobutyric acid metabolism | |
| dc.type | Article | |
| dc.rights.license | Public Domain | |
| local.college | Burnett School of Medicine | |
| local.department | Burnett School of Medicine | |
| local.persons | Papadelis (SOM) | |
