A new imaging study may be the first to provide direct in vivo evidence that tinnitus is associated with measurable changes in synaptic density across several brain regions, including those involved in auditory processing, emotion, and cognitive function. Additionally, the changes appear to differ between acute and chronic stages of the condition.
The research, titled "Direct Evidence for Synaptic Density Changes in Tinnitus: ¹⁸F-SynVesT-1 PET Reveals Novel Targets Beyond Metabolic Changes," was led by JiaYu Zhong and colleagues at Central South University and Hunan Normal University in China. It is currently available as a downloaded preprint on Elsevier’s Social Science Research Network (SSRN), a server that partners with The Lancet, and it is still pending peer review and acceptance for publication.
Synaptic Density Increases in Chronic Tinnitus
Using a specialized PET imaging tracer called ¹⁸F-SynVesT-1, which binds to a synaptic vesicle protein and serves as a proxy for synaptic density, researchers examined the brains of 28 individuals with tinnitus and 24 healthy controls. Participants also underwent a standard ¹⁸F-FDG PET scan, which measures general metabolic activity, and were evaluated via EEG and MRI.
They found that patients with chronic tinnitus exhibited increased ¹⁸F-SynVesT-1 uptake—suggesting elevated synaptic density—in 14 distinct brain regions. These included brain areas involved in auditory processing, emotion, and cognitive function. Only one region—the left inferior frontal gyrus—showed decreased uptake.
Interestingly, these areas largely overlapped with zones of elevated metabolism seen in traditional ¹⁸F-FDG PET scans. However, ¹⁸F-SynVesT-1 revealed a broader and more differentiated pattern of changes, suggesting this type of PET scan may be a more sensitive tool for assessing tinnitus-related neuroplasticity.
Acute Tinnitus Shows Opposite Trend
In contrast, patients with acute tinnitus showed a reduction in synaptic density across five brain regions. These findings suggest a bidirectional synaptic remodeling process, where the brain initially loses synaptic connectivity before undergoing compensatory growth in chronic stages.
The extent of synaptic changes was also correlated with tinnitus severity. Patients with higher Tinnitus Handicap Inventory (THI) scores had lower synaptic density in limbic structures, linking emotional distress to specific neurological alterations.
Network Reorganization and EEG Findings
In addition to PET scan results, brain network analysis revealed increased functional connectivity, especially during the acute phase. This suggests that the brain may respond to tinnitus with widespread reorganization, possibly adapting to the persistent internal sound.
EEG microstate analysis—used to assess the dynamics of large-scale brain networks—showed conserved alterations in patients with tinnitus, reinforcing the idea that the neural impact may be more widespread in the brain.
Implications for Tinnitus Research and Treatment
The new research is reported to be the first human imaging study to provide direct, in vivo evidence of synaptic remodeling in tinnitus, offering new insights into how the condition may evolve over time.
The different findings between acute and chronic cases challenge the notion of tinnitus as a static disorder; instead, they support emerging models that involve maladaptive neuroplasticity and central gain rebalancing.
The use of ¹⁸F-SynVesT-1—a newer PET tracer with growing use in Alzheimer’s and epilepsy research—may also pave the way for novel therapeutic strategies that target synaptic function rather than general neural excitability or auditory perception alone.
It should be acknowledged that PET tracers are an indirect method for measuring synaptic density; although widely used in Alzheimer’s and epilepsy research and strongly correlated with synaptic density in postmortem and animal studies, they do not provide a direct count of synapses (i.e., unlike a microscope count).
Study Sheds New Light on Tinnitus as an Auditory AND Neurobiological Issue
The new PET-related research may increase the importance of viewing tinnitus as a neurobiological condition with evolving brain changes, rather than a purely auditory or psychological issue. By identifying objective imaging biomarkers of synaptic density changes, the study could accelerate the development of more targeted treatments—and bring us closer to understanding the underlying brain mechanisms that sustain this often-debilitating condition.
Editor's note: This study, currently available as a preprint, has not yet undergone peer review and should be interpreted as early-stage evidence requiring further validation.
Preprint Study Citation:
Zhong J, Xiao X, Liu B, He Z, Zhou M, Hu S, Zhou E, et al. Direct Evidence for Synaptic Density Changes in Tinnitus: 18F-SynVesT-1 PET Reveals Novel Targets Beyond Metabolic Changes. SSRN. July 2025. Link to PDF preprint available at: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5353816
