Abnormal resting-state functional connectivity in the orbitofrontal cortex of heroin users and its relationship with anxiety: a pilot fNIRS study

Drug addiction is widely linked to the orbitofrontal cortex (OFC), which is essential for regulating reward-related behaviors, emotional responses, and anxiety. Over the past two decades, neuroimaging has provided significant contributions revealing functional and structural alternations in the brains of drug addicts. However, the underlying neural mechanism in the OFC and its correlates with drug addiction and anxiety still require further elucidation. We first presented a pilot investigation to examine local networks in OFC regions through resting-state functional connectivity (rsFC) using functional near-infrared spectroscopy (fNIRS) from eight abstinent addicts in a heroin-dependent group (HD) and seven subjects in a control group (CG). We discovered that the HDs manifested enhanced interhemispheric correlation and rsFC. Moreover, small-worldness was explored in the brain networks. In addition to the altered rsFC in the OFC networks, our examinations demonstrated associations in the functional connectivity between the left inferior frontal gyrus and other OFC regions related to anxiety in the HDs. The study provides important preliminary evidence of the complex OFC networks in heroin addiction and suggests neural correlates of anxiety. It opens a window in application of fNIRS to predict psychiatric trajectories and may create new insights into neural adaptations resulting from chronic opiate intake.

Experimental representation for the fNIRS-based rsFC analysis. A, The restingstate fNIRS recording session is followed by a gambling task recording session. During the task session (G, gambling), a subject was told that a number was hidden behind a card located in the center of a screen. The card would be displayed for three seconds, and the subject's task was to predict whether the number behind the card was bigger or smaller than five. At the end, the subject was told the number of corrections. The purpose of the gambling task was to simulate real-life anticipating and decision making of a subject who was asked to make the prediction. The HbO and Hb signals from the three-second fNIRS recordings data were extracted and analyzed to determine the stimuli-induced activation seed channel(s) for the rsFC analysis. The gambling task, adopted from The Human Connectome Project 1 , was presented by E-Prime software (E-Prime 2.0, Psychology Software Tools, Inc., Pittsburgh, PA, USA). B, The fNIRS data was analyzed accordingly from the corresponding recording session from the top in A. 3/9 Summary of the four-ROIs and their associated seed channels and the MNI coordinates. Channel coordinates were generated using the AtlasViewerGUI 2 program in Homer 2. Automated anatomical labeling (AAL) is applied.

ROIs
Channel    a NCG = 6, the channel was excluded due to a poor contact between the optodes. Similarity, C-D (second column), present the normalized values of γH , λH , γEH , and λEH of the HD network respectively. Almost all the values of γH and γEH > 1, and λH and λEH are = ~1, suggesting that the HD network is also small-world. The asterisk (*) represents a significant (p < 0.05/2 = 0.025; 2 statistical tests) difference between the small-world measures of the HDs and CGs at Sparsity = 0.14.
Scatter plot of small-worldness network measures. The mean Sigma values are plotted as a function of sparsity in the range between 0 and 1. The blue displays the small-world characteristics of the HD brain network with respect to the random network.
The red displays the characteristics of the CG brain network with respect to the random network. The green displays the HD brain network with respect to the CG brain network.
The error bars show the standard deviations.
Medication and substance-use status of subjects at the time of the study. Two HD subjects were undergoing the methadone (40 mg per day) maintenance treatment. One HD subject was taking simvastatin (20 mg). One CG subject reported to take trazodona (50 mg) in life time but reported not taking it during the period of the study. The urine screening reports of all the participants showed negative results (the absence) of amphetamine, oxycodone, heroin, morphine, codeine, tetrahydrocannabinol, cocaine, benzodiazepine, diazepam, and their metabolites. All the participants were chronic and heavy smokers. Our result showed that the year of smoking was significantly correlated with the STAI scores on a population level of the sample (R 2 = 0.550, p = 0.021, N = 15).