Multivariate morphological brain signatures predict patients with chronic abdominal pain from healthy control subjects

Abstract

Irritable bowel syndrome (IBS) is the most common chronic visceral pain disorder. The pathophysiology of IBS is incompletely understood; however, evidence strongly suggests dysregulation of the brain-gut axis. The aim of this study was to apply multivariate pattern analysis to identify an IBS-related morphometric brain signature that could serve as a central biological marker and provide new mechanistic insights into the pathophysiology of IBS. Parcellation of 165 cortical and subcortical regions was performed using FreeSurfer and the Destrieux and Harvard-Oxford atlases. Volume, mean curvature, surface area, and cortical thickness were calculated for each region. Sparse partial least squares discriminant analysis was applied to develop a diagnostic model using a training set of 160 females (80 healthy controls and 80 patients with IBS). Predictive accuracy was assessed in an age-matched holdout test set of 52 females (26 healthy controls and 26 patients with IBS). A 2-component classification algorithm comprising the morphometry of (1) primary somatosensory and motor regions and (2) multimodal network regions explained 36% of the variance. Overall predictive accuracy of the classification algorithm was 70%. Small effect size associations were observed between the somatosensory and motor signature and nongastrointestinal somatic symptoms. The findings demonstrate that the predictive accuracy of a classification algorithm based solely on regional brain morphometry is not sufficient, but they do provide support for the utility of multivariate pattern analysis for identifying meaningful neurobiological markers in IBS.

Figure 1

Axial (A) and coronal (B) views of regional parcellations based on the Destrieux and Harvard-Oxford subcortical atlas in a representative subject.

Figure 2. Individual sample plot

Irritable bowel syndrome (red) and healthy control (blue) are represented as point placed according to their scores on the two brain signatures derived from a sparse partial least squares-discriminative analysis. This plot suggests group discrimination can be obtained with the morphological classifier.

Figure 3. Regions comprising the Brain signature 1

Using Freesurfer, all regions comprising the signatures are depicted on an inflated brain labeled with the Destrieux Atlas. Table 2 contains the describes the morphological measures (Volume, Cortical thickness, surface area and/or mean curvature) of the regions that contributed to the solutions

1. Brain Signature 1 regions-Lateral View: 4, Subcentral Gyrus (central operculum) and Sulci; 15, Middle Frontal Gyrus (15); 28, Postcentral Gyrus; 29, Precentral Gyrus; 38, Middle Temporal Gyrus; 45, Central Sulcus (Rolando’s Fissure); 47, Anterior Segment of the Circular Sulcus of the Insula; 49, Superior Segment of the Circular Sulcus of the Insula; 69, Superior Part of the Precentral Sulcus

2. Brain Signature 1 regions-Medial View : 3, Paracentral Lobule and Sulcus; 8, Middle-Posterior Part of the Cingulate Gyrus and Sulcus (pMCC); 16, Superior Frontal Gyrus 66, Pericallosal Sulcus (Sulcus of Corpus Callosum); 70, Suborbital Sulcus (Sulcus Rostrales, Supraorbital Sulcus)

Figure 3. Regions comprising the Brain signature 1

Using Freesurfer, all regions comprising the signatures are depicted on an inflated brain labeled with the Destrieux Atlas. Table 2 contains the describes the morphological measures (Volume, Cortical thickness, surface area and/or mean curvature) of the regions that contributed to the solutions

1. Brain Signature 1 regions-Lateral View: 4, Subcentral Gyrus (central operculum) and Sulci; 15, Middle Frontal Gyrus (15); 28, Postcentral Gyrus; 29, Precentral Gyrus; 38, Middle Temporal Gyrus; 45, Central Sulcus (Rolando’s Fissure); 47, Anterior Segment of the Circular Sulcus of the Insula; 49, Superior Segment of the Circular Sulcus of the Insula; 69, Superior Part of the Precentral Sulcus

2. Brain Signature 1 regions-Medial View : 3, Paracentral Lobule and Sulcus; 8, Middle-Posterior Part of the Cingulate Gyrus and Sulcus (pMCC); 16, Superior Frontal Gyrus 66, Pericallosal Sulcus (Sulcus of Corpus Callosum); 70, Suborbital Sulcus (Sulcus Rostrales, Supraorbital Sulcus)

Figure 4. Regions comprising the Brain signature 2

Using Freesurfer, all regions comprising the signatures are depicted on an inflated brain labeled with the Destrieux Atlas. Table 2 contains the describes the morphological measures (Volume, Cortical thickness, surface area and/or mean curvature) of the regions that contributed to the solutions

1. Brain Signature 2 regions-Lateral View:

   41, Posterior Ramus of the Lateral Sulcus; 47, Anterior Segment of the Circular Sulcus of the Insula; 69, Superior Part of the Precentral Sulcus; 56, Intraparietal Sulcus and Transverse Parietal Sulci ; 74, Transverse Temporal Sulcus

2. Brain Signature 2 regions- Medial View:

   21 Lateral Occipito-Temporal Gyrus (Fusiform Gyrus); 32, Subcallosal Area (Subcallosal Gyrus);

Figure 4. Regions comprising the Brain signature 2

Using Freesurfer, all regions comprising the signatures are depicted on an inflated brain labeled with the Destrieux Atlas. Table 2 contains the describes the morphological measures (Volume, Cortical thickness, surface area and/or mean curvature) of the regions that contributed to the solutions

1. Brain Signature 2 regions-Lateral View:

   41, Posterior Ramus of the Lateral Sulcus; 47, Anterior Segment of the Circular Sulcus of the Insula; 69, Superior Part of the Precentral Sulcus; 56, Intraparietal Sulcus and Transverse Parietal Sulci ; 74, Transverse Temporal Sulcus

2. Brain Signature 2 regions- Medial View:

   21 Lateral Occipito-Temporal Gyrus (Fusiform Gyrus); 32, Subcallosal Area (Subcallosal Gyrus);