ReachRxResearch
Home
Research
Sign Up
  1. Home
  2. Research Hub
  3. Inferring brain-wide interactions using…

Inferring brain-wide interactions using data-constrained recurrent neural network models

Neuron·August 7Open Access
NeurosciencesLimited evidenceDrug-Resistant EpilepsyMemory RetrievalMulti-Region Neural DynamicsPavlovian ConditioningMethodological Development With Experimental ValidationRecurrent Neural Network Computational ModelingMixed

Summary

View source

What was studied

This study introduces Current-Based Decomposition (CURBD), a computational framework that fits data-constrained recurrent neural network (RNN) models to multi-region neural recordings to infer the magnitude and directionality of inter-region currents. It was validated on simulated ground-truth networks, then applied to calcium imaging in mice (4 cortical regions, spontaneous running), electrophysiology pseudopopulations in macaques (amygdala, ACC, striatum; Pavlovian conditioning), and single-unit recordings in 5 human epilepsy patients (hippocampus/amygdala, preSMA, dACC; memory retrieval).

Key findings

CURBD accurately recovered ground-truth inter-region currents in simulations down to 5% neuronal subsampling (VAF up to 0.98 for key current sources). In mice, M2-to-V1 currents best decoded running speed. In macaques, striatum-to-ACC currents were strong after water reward but ACC-to-striatum currents only emerged bidirectionally after juice reward—an asymmetry consistent across both monkeys and 5 RNN initializations. In humans, preSMA-to-H/A currents specifically increased for familiar images, while novel images recruited large sustained currents across the whole network.

Study limitations

- Inferred directed interactions reflect functional, not anatomical, connectivity and cannot establish causality. - The model assumes a single static directed interaction matrix across the entire recording period, which may miss learning- or state-dependent changes. - Human and monkey datasets relied on pseudopopulations (non-simultaneously recorded neurons averaged across trials), which may not capture single-trial dynamics.

Clinical implications

CURBD is not a clinical intervention but is a freely available computational tool (github.com/rajanlab/CURBD) that neuroscientists and clinicians studying multi-region brain dynamics—including in human intracranial recordings—can apply to infer directional inter-area communication without requiring simultaneous recordings or known anatomical connectivity.

Caveats

  • CURBD infers functional, not anatomical, directed interactions—strong inferred currents may reflect polysynaptic or neuromodulatory pathways rather than direct connections. Clinical or mechanistic interpretations should account for this.
  • Study design is difficult to classify by standard hierarchy; it combines computational methods development, simulation validation, and cross-species experimental application. Level of evidence (5) reflects the observational/proof-of-concept nature of experimental applications.
  • The paper was originally posted as a preprint in March 2021; the journal publication date is August 2026. Some citations and framing may reflect the earlier preprint context.
Show all 4
  • The sample_size tag reflects the human participant cohort (n=5); the full study spans multiple species (mice n=2, macaques n=2, humans n=5) and is primarily a methods paper without a single unified N. Interpret sample sizes per experiment accordingly.

Related Questions

Explore related topics

How do recurrent neural network models infer directional communication between brain regions in multi-region electrophysiology data?What computational methods can identify inter-area information flow from human intracranial recordings during memory tasks?How does striatum-to-ACC versus ACC-to-striatum signaling differ across reward magnitudes in Pavlovian conditioning?

Publication Details

Year
2026
Journal
Neuron
Sample Size
n=5
Source
View article
Keep scrolling
More content below.
Up Next