Tinception

Multiscale Profiling of the Tinnitus Brain: From Individual Subcortical Deviations to GABAergic and Dopaminergic Molecular Architectures

Abstract

Chronic tinnitus is a debilitating phantom perception characterized by maladaptive neuroplasticity. Despite numerous studies, the transition from macroscale structural remodeling to specific molecular pathways remains poorly understood. We hypothesized that tinnitus-related structural deviations are not spatially random but are anchored to specific subcortical hubs defined by distinct transcriptomic profiles and shared genetic risk for sensory gating dysfunction.

Methods: We integrated four levels of analysis:

Macroscale Neuroimaging: We utilized Voxel-Based Morphometry (VBM), Surface-Based Morphometry (SBM), and Structural Similarity Gradients to map the organizational hierarchy of tinnitus-related changes.

Individual Precision: Normative Modeling was applied to quantify individual deviations from healthy population benchmarks Discovery, mapping these onto subcortical subsegmentations (e.g., Pulvinar sub-nuclei).

Molecular Virtual Biopsy: These structural "hotspots" were integrated with the Allen Human Brain Atlas (abagen) to identify the gene expression profiles driving regional vulnerability.

Genetic Validation: Finally, we tested the clinical relevance of these findings in the UK Biobank (N≈40,000) using Enhanced Polygenic Risk Scores (PRS) for traits sharing similar synaptic architectures.

Installation

• Ensure your Python 3.9+ installation path is defined in your system's PATH.

• Clone the repository:

  git clone git@github.com:payamsash/tinception.git

with venv

• Set up a virtual environment (optional but recommended):

  python -m venv venv
  source venv/bin/activate  # On Windows: .\env\Scripts\activate
  pip install -r requirements.txt