2026-08-18 14:08 | Source: Department of Nuclear Medicine Imaging, Southwest Hospital, Army Medical University | PET Neuroimaging | Positron Emission Tomography

On August 17, Professor Liu Chen and Professor Wang Jian's team from the Department of Radiology at Southwest Hospital, Army Medical University, in collaboration with Professor Long Zhiliang's team from the School of Psychology at Southwest University, systematically elucidated the underlying molecular pathological mechanisms of macroscopic brain network decoupling in patients with Spinocerebellar Ataxia Type 3 (SCA3) by integrating multimodal magnetic resonance imaging with high-resolution microscale biological atlases. This work provides a novel perspective and objective imaging biomarkers for addressing the clinical-radiological dissociation challenge in clinical diagnosis and treatment. The findings were published in Movement Disorders, an international top-tier journal in the field of neuro-motor disorders, under the title: "Striatal Structure-Function Decoupling as an Early Candidate Imaging Biomarker for Motor Impairment Severity in Spinocerebellar Ataxia Type 3."

"SCA3 is the most common autosomal dominant ataxia worldwide, caused by abnormal CAG (cytosine-adenine-guanine) repeat expansion in the ATXN3 (ataxin-3) gene, which severely impairs patients' motor function," explained Liu Chen. "In long-term clinical practice, physicians often face a vexing dilemma—the clinical-radiological dissociation phenomenon—where the degree of macroscopic brain atrophy in patients frequently fails to fully account for the severity of their clinical motor symptoms."

"More critically, although the scientific community has recognized the role of altered brain structure and functional connectivity in neurodegenerative diseases, the maintenance of synchronized neural activity depends not only on structural connections at the physical level but also on efficient mitochondrial energy supply and precise synaptic regulation. How these microscale molecular pathologies drive macroscopic imaging phenotypes has not been systematically elucidated," Liu added.

To investigate this core mechanism, the research team conducted a hypothesis-driven, prospective, two-center, multimodal imaging study, enrolling a large cohort of genetically confirmed SCA3 patients and healthy controls. Using cutting-edge algorithms, they quantified the structure-function coupling index of the subjects' brains—that is, the degree of协同 matching between physical structural connections and actual neural functional activity. Building on this, the team performed spatial mapping analyses, correlating changes in macroscopic brain network coupling with the latest brain mitochondrial proteomic atlas, the Allen Human Brain Atlas transcriptome, and PET-based neurotransmitter receptor atlases. This frontier cross-disciplinary approach in imaging transcriptomics successfully bridged macroscopic neuroimaging phenotypes and microscale molecular pathology at the living (in vivo) level.

"The study found that SCA3 patients exhibit significant structure-function decoupling independent of brain atrophy even in the early stages of the disease, and the degree of decoupling is highly correlated with the severity of clinical ataxia symptoms," Liu stated. "The team also precisely identified the bilateral dorsolateral putamen as a core brain region, whose abnormal signals exhibit both sensitivity and stability, and which has the potential to serve as a convenient imaging 'ruler' to assist physicians in early quantification of motor impairment progression. More importantly, the study demonstrated that this macroscopic network disruption is not random—it deeply overlaps with inherent vulnerable regions at the brain's microscale, including mitochondrial complex II involved in energy metabolism, 5-hydroxytryptamine 2A and 5-hydroxytryptamine 4 receptor densities that influence neurotransmission, and gene expression enrichment regions responsible for synaptic plasticity and cellular homeostasis regulation."

"These findings provide clinically actionable, objective, and precise imaging targets that reflect early SCA3 pathology, and for the first time confirm that brain network decoupling is one of the core early pathological features of SCA3, while clarifying the underlying microscale genetic, mitochondrial, and neurotransmitter receptor mechanisms—greatly advancing the medical community's understanding of SCA3 pathogenesis," Liu concluded.

In the next step, the research team plans to conduct larger-scale, multicenter, long-term follow-up studies to further validate the reliability and clinical generalizability of the bilateral dorsolateral putamen structure-function decoupling imaging biomarker across broader patient populations.

Source link: https://www.cinie.net/article/61208.html

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