Mapping Functional Brain Activity and Connectivity in Delirium with Diffuse Optical Tomography

Background:
Delirium is the most common neuropsychiatric syndrome in the hospital, yet it remains understudied. Most of the published data is focused on clinical manifestations and not underlying pathophysiology or mechanisms. Functional neuroimaging would be beneficial; however there has been no device that can capture three-dimensional data at bedside. The primary objective of this study was to determine if diffuse optical tomography (DOT) can be used to obtain resting-state and task-based functional data during and after an episode of delirium. Secondary objectives include correlating regional dysfunction with severity scores and clinical variables.

Methods:
This single-center exploratory study was conducted at a tertiary hospital. Two groups of patients were recruited: a delirium group and a non-delirious group matched for age/gender/hand/admission setting. The delirium group included patients formally diagnosed by a consultation-liaison psychiatrist (DSM-V criteria) and documented by a positive 4AT (general ward) or CAM-ICU score (ICU). Subjects were evaluated daily and delirium resolution was defined as at least two consecutive days of negative screening. The Delirium Rating Scale-R-98 (DRS-R-98) was used to measure severity of delirium. Subtypes were classified based on Liptzin-Levkoff criteria. The APACHE III and the Charlson Comorbidity Index were used to quantify acute illness severity and burden of chronic disease, respectively.

A custom DOT system was employed. Continuous-wave measurements of data were captured through a 48 source-detector head interface. Regions of interest were identified based on Montreal Neurological Institute coordinates centered on the prefrontal cortex. The protocol consisted of a two-minute resting state scan, followed by a one-minute task (Months Backwards Test), and then another two-minute resting scan. Images were collected at time of enrollment and then after resolution of delirium. Seed-based correlation analysis (SCA) with the left dorsolateral prefrontal cortex (DLPFC) set as the seed region was conducted as well.

Results:

25 delirious subjects and 25 non-delirious subjects were recruited (n=50). In all regions, the total hemoglobin values were statistically significantly decreased in the delirium group, even after resolution of delirium (p=0.015; 95% CI [0.5, 0.92] and p=0.023; 95% CI [1.2, 2.05]. The time to peak hemoglobin value and return to resting state was also delayed (p=0.027). DRS-R-98 scores correlated with hemoglobin values in all regions. SCA revealed that left DLPFC activity was more strongly associated with right DLPFC and dorsomedial prefrontal cortex (DMPFC) activity post-resolution and in non-delirious subjects relative to during an episode of delirium.

Conclusion:

To date, this is the largest delirium functional neuroimaging study with a matched control group that reveals marked prefrontal functional dysconnectivity during and even after an episode of delirium. These findings demonstrate the feasibility of a portable DOT imaging system for biomarker studies in delirium. Future studies will focus on post-delirium neurocognitive impairment and the relationship between delirium and subsequent Alzheimer’s disease and related dementias.

References:

Jiang, H. (2010). Diffuse Optical Tomography: Principles and Applications (1st ed.). CRC Press.

Nitchingham A, Kumar V, Shenkin S, Ferguson KJ, Caplan GA. A systematic review of neuroimaging in delirium: predictors, correlates and consequences. Int J Geriatr Psychiatry. 2018;33(11):1458-1478.