Default mode network connectivity predicts sustained attention deficits after traumatic brain injury

Abstract

Traumatic brain injury (TBI) frequently produces impairments of attention in humans. These can result in a failure to maintain consistent goal-directed behavior. A predominantly right-lateralized frontoparietal network is often engaged during attentionally demanding tasks. However, lapses of attention have also been associated with increases in activation within the default mode network (DMN). Here, we study TBI patients with sustained attention impairment, defined on the basis of the consistency of their behavioral performance over time. We show that sustained attention impairments in patients are associated with an increase in DMN activation, particularly within the precuneus and posterior cingulate cortex. Furthermore, the interaction of the precuneus with the rest of the DMN at the start of the task, i.e., its functional connectivity, predicts which patients go on to show impairments of attention. Importantly, this predictive information is present before any behavioral evidence of sustained attention impairment, and the relationship is also found in a subgroup of patients without focal brain damage. TBI often results in diffuse axonal injury, which produces cognitive impairment by disconnecting nodes in distributed brain networks. Using diffusion tensor imaging, we demonstrate that structural disconnection within the DMN also correlates with the level of sustained attention. These results show that abnormalities in DMN function are a sensitive marker of impairments of attention and suggest that changes in connectivity within the DMN are central to the development of attentional impairment after TBI.

Figure 1.

Overview of the methods used to analyze behavioral and brain changes during the performance of the CRT.

Figure 2.

Impairments of sustained attention after TBI are associated with increased DMN activity. A, Brain regions that increase activation more in patients than controls for Go (Go3–Go1) and Rest trials (Rest3–Rest1). B, Brain regions that increase activation more in patients with low SA than those with high SA. Results are superimposed on the MNI 152 T1 1 mm brain template. A Z-statistic threshold of 2.3 combined with a corrected cluster significance threshold probability of p < 0.05 was used. R, Right. C, D, The two bottom graphs represent the percentage BOLD signal change in the precuneus/PCC (−4, −68, 34) for the contrasts Go3–Go1 and Rest3–Rest1 in controls (blue) and patients (orange) (C), and in high-SA (yellow) and low-SA (red) patients (D).

Figure 3.

Behavioral results for the first (T1) and the last (T3) third of the choice reaction task. Controls (light gray), high-SA TBI patients (middle gray), and low-SA patients (dark gray) are shown. A, Mean reaction time in seconds. B, IIV ± SEM. C, Percentage accuracy ± SEM. **p < 0.001; *p < 0.05; Statistical significance. Light gray asterisk refers to p < 0.1 difference between low-SA patients at T1 and T3.

Figure 4.

Low functional connectivity within the DMN predicts impairment in sustained attention after TBI. A, Reference ICA component showing the default mode network (warm colors) and an anticorrelated executive control/salience network (cold colors). Activations are superimposed on MNI 152 T1 1 mm brain template axial sections from z = −12 to z = 46. R, Right. B, In patients, precuneus integration during the first part of the task is correlated with the degree of sustained attention impairment that subsequently develops. Functional connectivity of the precuneus during the first third of the task (T1) is plotted against change in RT between the first and the last part of the task in controls (left graph; gray lozenges; N = 26) and in patients (right graph; black circles; N = 28). Measures are age normalized, i.e., age was regressed out from the measures using a linear regression, and residuals were saved as standardized values.

Figure 5.

The structure of the right cingulum bundle is correlated with sustained attention impairment. A, Sagittal view (x = 4) of the reference component selected for the functional connectivity analysis (Fig. 4). Anterior and posterior midline nodes of the DMN are shown in warm colors, and the midline node within the EN is shown in blue. The right cingulum bundle connecting the posterior and anterior parts of the DMN is shown in green. B, FA of the cingulum bundle in patients is plotted against the change in RT between the first and the last part of the task (N = 28). Measures are age normalized, i.e., age was regressed out from the measures using a linear regression, where residuals were saved as standardized values.