Longitudinal Changes of Caudate-Based Resting State Functional Connectivity in Mild Traumatic Brain Injury

Abstract

Mild traumatic brain injury (mild TBI) is associated with dysfunctional brain network and accumulating evidence is pointing to the caudate as a vulnerable hub region. However, little is known about the longitudinal changes in the caudate-based resting-state functional connectivity following mild TBI. In the current study, 50 patients with mild TBI received resting-state functional magnetic resonance imaging as well as neuropsychological assessments within 7 days post-injury (acute phase) and 1 month later (subacute phase). Thirty-six age- and gender- matched healthy controls underwent the same protocol. The caudate was segmented into the dorsal and ventral sub-regions based on their related functionally distinct neural circuits and separate functional connectivity was investigated. Results indicated that patients with mild TBI at acute phase exhibited reduced left dorsal caudate-based functional connectivity with ventral lateral prefrontal cortex, dorsal anterior cingulate cortex, and inferior parietal lobule, which mainly distributed in the cognitive control network, and reduced right ventral caudate-based functional connectivity with the dorsal lateral prefrontal cortex, dorsal anterior cingulate cortex (dACC), and bilateral ventral anterior cingulate cortex (vACC), which mainly distributed in the executive network and emotional processing network. Furthermore, patients with mild TBI presented the reduced functional connectivity between the left dorsal caudate and the ventral lateral prefrontal cortex (vlPFC) compared with healthy controls at acute phase while this difference became no significance and return to the normal level following 1 month post-injury subacute phase. Similarly, the functional connectivity between the right ventral caudate and anterior cingulate cortex (both dorsal and ventral part) showed the reduced strength in patients compared with healthy controls only at the acute phase but presented no significant difference at subacute phase following mild TBI. Along the same line, patients with mild TBI presented the impaired performance on the information processing speed and more complaints on the pain impact index at acute phase compared with healthy controls but showed no significant difference at the follow-up 1 month post-injury subacute phase. The longitudinal changes of caudate-based dysfunction connectivity could serve as a neuroimaging biomarker following patients with mild TBI, with the evidence that the abnormal caudate-based functional connectivity at acute phase have returned to the normal level accompanying with the recovery of the neuropsychological syndromes following patients with mild TBI at subacute phase.

Keywords: a neuroimaging biomarker; caudate; dysfunction; longitudinal changes; mild traumatic brain injury.

Figure 1

Representation of the 4 caudate regions of interest. The above panel shows the projection of the 2 left caudate regions, left dorsal caudate (red), and left ventral caudate (blue), onto sagittal brain views for x = −18, −16, −14, −12; The below panel shows the projection of the 2 right caudate regions, right dorsal caudate (green), and right ventral caudate (yellow), onto sagittal brain views for x = 12, 14, 16, 18, respectively.

Figure 2

(A) Bar graph shows the decreased performance of clinical symptom (HIT-6) scales as a function of time (acute phase to subacute phase) with patients with mild TBI (red) but not healthy controls (green). (B) Bar graph shows the increased performance of cognitive function (DSC) scales as a function of time (acute phase to subacute phase) with patients with mild TBI (red) but not healthy controls (green). “n.s” marks p > 0.05, and error bar represents standard deviations of the mean.

Figure 3

Regions demonstrating group differences in mean FC (functional connectivity) strength for the left dorsal caudate seed (A) and right ventral caudate seed (C) at acute phase. Red coloring indicates regions where the functional connectivity strength was significantly decreased for patients with mild TBI, compared with HC. The bar charts display mean functional connectivity strength between selected significant regions within the left dorsal caudate seed (B) and right ventral caudate seed (D) above for mild TBI (red) and HC (green). Error bars illustrate standard deviations of the mean. Coordinates for slice locations are presented according to the MNI atlas, and cluster volumes are presented in Table 3. L,Left; R,Right.

Figure 4

Scatterplots of Functional Connectivity (FC) strength of significant regions are displayed for mild TBI (open triangles) and HC (open circles) at acute phase and subacute phase. Each symbol represents a single individual's FC strength. The I bars indicate the means and standard deviation. The p-values were obtained from group mean difference. (A) Left dorsal caudate-vlPFC functional connectivity. (B) Right ventral caudate-dACC functional connectivity. (C) Right ventral caudate-rvACC functional connectivity.