Multimodal Brain MRI of Deep Gray Matter Changes Associated With Inflammatory Bowel Disease

Abstract

Background: Behavioral symptoms, including mood disorders, substantially impact the quality of life of patients with inflammatory bowel disease (IBD), even when clinical remission is achieved. Here, we used multimodal magnetic resonance imaging (MRI) to determine if IBD is associated with changes in the structure and function of deep gray matter brain regions that regulate and integrate emotional, cognitive, and stress responses.

Methods: Thirty-five patients with ulcerative colitis (UC) or Crohn's disease (CD) and 32 healthy controls underwent 3 Tesla MRIs to assess volume, neural activity, functional connection strength (connectivity), inflammation, and neurodegeneration of key deep gray matter brain regions (thalamus, caudate, pallidum, putamen, amygdala, hippocampus, and hypothalamus) involved in emotional, cognitive and stress processing. Associations with sex, presence of pain, disease activity, and C-reactive protein (CRP) concentration were examined.

Results: Significantly increased activity and functional connectivity were observed in cognitive and emotional processing brain regions, including parts of the limbic system, basal ganglia, and hypothalamus of IBD patients compared with healthy controls. Inflammatory bowel disease patients exhibited significantly increased volumes of the amygdala and hypothalamus, as well as evidence of neurodegeneration in the putamen and pallidum. Hippocampal neural activity was increased in IBD patients with active disease. The volume of the thalamus was positively correlated with CRP concentration and was increased in females experiencing pain.

Conclusions: Patients with IBD exhibit functional and structural changes in the limbic and striatal systems. These changes may be targets for assessing or predicting the response to therapeutic interventions aimed at improving comorbid emotional and cognitive symptoms.

Keywords: IBD; MRI; amygdala; basal ganglia; brain.

Figure 1.

Inflammatory bowel disease patients exhibited significantly greater ALFF of the hippocampus, hypothalamus, thalamus, insula, putamen, caudate, and pallidum relative to controls (CTRL). For the putamen and pallidum, the difference between IBD patients and controls was observed in females only. The image at the lower right shows the anatomical location of the regions of interest on a standardized brain template image, including those that exhibited a significant group difference (in red) and those where the group difference was observed in females only (in yellow) (See online version for color figures).

Figure 2.

Inflammatory bowel disease patients exhibited significantly reduced susceptibility in the (A) putamen and (B) pallidum, relative to controls (CTRL).

Figure 3.

Functional deep gray matter brain region connections (in yellow) whose connectivity was significantly increased in IBD patients relative to controls, including the insula-hypothalamus, insula-hippocampus, insula-putamen, insula-pallidum, putamen-hypothalamus, putamen-pallidum, putamen-caudate, pallidum-hypothalamus, caudate-hippocampus, and caudate-thalamus connections (See online version for color figures).

Figure 4.

A, Inflammatory bowel disease patients exhibited significantly greater volume of the amygdala. B, In IBD patients, the volume of the amygdala increased in patients with mild disease activity (MILD) vs those with moderate/severe activity (MOD) in females (F), whereas males (M) exhibited no change in amygdala volume associated with changes in disease activity. C, The change in amygdala ALFF for males, from control to IBD was greater than the change in females. D, IBD patients exhibited significantly greater volume of the hypothalamus. An increase in (E) hypothalamus-hippocampus and (F) hypothalamus-thalamus connectivity between control and IBD patient groups occurred in females but not males.

Figure 5.

A, Thalamus volume for female (F) IBD patients experiencing pain (P) was increased relative to female IBD patients not experiencing pain (NP), but pain was not associated with thalamus volume in male (M) IBD patients. B, IB7D patients with moderate/severe disease (MOD) activity not experiencing pain exhibited a lower thalamic volume compared with patients with mild disease activity (MILD); patients experiencing pain showed no changes with disease activity. C, ALFF of the hippocampus was significantly greater in IBD patients with moderate/severe disease activity relative to mild disease/remission. (D) The volume of the thalamus and (E) functional connectivity between the thalamus and pallidum were significantly correlated with log₁₀ CRP concentration.