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SPACE-fmri-change Analysis Pipeline

Analysis code for the SPACE (Supportive Parenting for Anxious Childhood Emotions) fMRI change study: neuroimaging and clinical-outcome analyses of an emotion face processing task collected pre- and post-treatment, under parent-accompanied and alone scan conditions, across two randomized-controlled-trial phases (Phase I: SPACE vs. PE; Phase II: SPACE vs. CBT).This repo contains the complete analysis pipeline underlying the reported neuroimaging and clinical results.

Pipeline Stages

Script Stage Produces
01_aggregate_data.sh Data aggregation (HPC) Smoothed, condition-contrasted first-level activation volumes
02_extract_roi_activation.py ROI extraction (HPC) Per-subject Shen 368-parcel median activation (long format)
03_create_clinical_brain_volumes.py Covariate volumes (HPC) Per-subject symptom-score brain volumes for downstream masking
04_build_final_datasets.py Dataset construction 5 FINAL analysis datasets (Phase I/II x ITT/PP, cross-phase)
05_neuroimaging_lme.R Primary neuroimaging analysis Table 3, Figure 2 — hierarchical TIME x TX x CONDITION LMEs per ROI
06_clinical_outcomes_lme.R Primary clinical analysis Tables 1-2, Figure 1 — TIME x TX LMEs for PARS/FASA-P/FASA-C
07_clinical_neuro_subsamples.R Supplementary clinical analysis Clinical LMEs restricted to the neuroimaging subsamples
08_scanner_sensitivity.R Sensitivity analysis Leave-two-out refit excluding subjects scanned on a different scanner
09_phase_sensitivity.R Sensitivity analysis Permutation test distinguishing power loss from Phase I-specific effects
10_qc_selection_analysis.py Selection-bias analysis QC-included vs. QC-excluded participant comparison
11_plot_amygdala_3way.R Figure generation Phase II amygdala TIME x TX x CONDITION interaction plot

Shared logic used by more than one numbered script is factored into four helper files, each sourced by the scripts that need it:

Helper Used by
data_loading_helpers.R 05, 08, 09, 11
neuro_lme_helpers.R 05, 08
neuro_plot_helpers.R 05, 11
clinical_lme_helpers.R 06, 07

Dependencies

R (developed against R 4.3.1): lme4, lmerTest, ggplot2, dplyr, ggExtra, lavaan, grid, patchwork, stringr, ggpubr, tidyr, foreach, doParallel.

Python: numpy, pandas, scipy, joblib, nibabel, pyreadstat.

External tools: AFNI (3dmaskave, 3dmerge, 3dcalc) for stages 1-2; an HPC environment with an environment-module system (module load AFNI) for stages 1-3, which are designed to run on a compute cluster rather than locally.

Usage

Run the numbered scripts in order; each stage's output feeds the next. Stages 1-3 require raw imaging data and AFNI/HPC access and are not reproducible outside that environment; stages 4 onward operate on the tabular outputs of stages 1-3 and can be run on any machine with the Python/R dependencies above installed.

bash 01_aggregate_data.sh              # HPC only
python 02_extract_roi_activation.py    # HPC only
python 03_create_clinical_brain_volumes.py   # HPC only
python 04_build_final_datasets.py
Rscript 05_neuroimaging_lme.R
Rscript 06_clinical_outcomes_lme.R
Rscript 07_clinical_neuro_subsamples.R
Rscript 08_scanner_sensitivity.R
Rscript 09_phase_sensitivity.R
python 10_qc_selection_analysis.py
Rscript 11_plot_amygdala_3way.R

Scripts 05-11 use control flags (near the top of each file) to toggle optional branches (e.g. exploratory post-hoc reporting, SEM, residualization); all flags default to the setting used for the reported manuscript results.

Note on file paths: scripts in this directory read their base directories from environment variables (e.g. SPACE_BASE, SPACE_DATA_DIR, SPACE_OUT_DIR) with placeholder defaults. Set these variables to point to the location of the corresponding input files before running the scripts in your environment.

About

Analysis code for Keding et al. documenting functional brain changes associated with SPACE, a parent-based treatment for child anxiety.

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