SSADHD

Succinic semialdehyde dehydrogenase deficiency

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a genetic metabolic disorder in which the breakdown of γ-aminobutyric acid (GABA) is impaired, leading to its accumulation along with γ-hydroxybutyric acid (GHB). While GABA is widely known as the main inhibitory neurotransmitter in the brain, it also influences the development of myelin, the insulating layer around nerve fibers. This study investigated whether high levels of GABA and GHB in SSADHD are associated with abnormal myelination.

Researchers reviewed brain MRIs from 23 SSADHD patients and 21 healthy controls using a specialized myelination scoring system. They found that SSADHD patients had mild but significantly greater dysmyelination than controls. Lower myelination scores were strongly linked to younger age and higher plasma levels of GABA and GHB, suggesting that myelination deficits are more pronounced early in life. In a mouse model of SSADHD, genes related to myelin formation were expressed at lower levels, supporting impaired oligodendrocyte maturation.

These findings suggest that excessive GABA and GHB may delay myelin development in SSADHD. Understanding this relationship may help monitor disease progression and could provide insight into other white-matter disorders.

Brain plasticity

Assessing the mechanisms of brain plasticity by TMS

Transcranial magnetic stimulation (TMS) is a non-invasive technique for focal brain stimulation based on electromagnetic induction where a fluctuating magnetic field induces a small intracranial electric current in the brain. For more than 35 years, TMS has shown promise in the diagnosis and treatment of neurological and psychiatric disorders in adults. In this review, we provide a brief introduction to the TMS technique with a focus on repetitive TMS (rTMS) protocols, particularly theta-burst stimulation (TBS), and relevant rTMS-derived metrics of brain plasticity. We then discuss the TMS-EEG technique, the use of neuronavigation in TMS, the neural substrate of TBS measures of plasticity, the inter- and intraindividual variability of those measures, effects of age and genetic factors on TBS aftereffects, and then summarize alterations of TMS-TBS measures of plasticity in major neurological and psychiatric disorders including autism spectrum disorder, schizophrenia, depression, traumatic brain injury, Alzheimer’s disease, and diabetes. Finally, we discuss the translational studies of TMS-TBS measures of plasticity and their therapeutic implications.