Dependence to opiates, including illicit heroin and prescription pain killers, and treatment of the opioid use disorder (OUD) have been longstanding problems over the world. Despite intense efforts to scientific investigation and public health care, treatment outcomes have not significantly improved for the past 50 years. One reason behind the continuing use of heroin worldwide despite such efforts is its highly addictive nature. Brain imaging studies over the past two decades have made significant contribution to the understanding of the addictive properties as to be due in part to biological processes, specifically those in the brain structure and function. Moreover, traditional clinical neuropsychology studies also contribute to the account in part for the treatment-refractory nature of the drug abuse. However, there is a gap between those studies, and the rates of relapse are still high. Thus, a multidisciplinary approach is needed to understand the fundamental neural mechanism of OUD. How does the brain of an OUD patient functionally and cognitively differ from others? This brief review is to compare and contrast the current literature on non-invasive resting state neuroimaging and clinical neuropsychological studies with the focus on the abstinence stage in OUD. The results show as follow: Brain connectivity strength in the reward system, dysregulation of circuits associated with emotion and stress, enhanced beta and alpha power activity, and high impulsivity are induced by OUD.Some recovery signs in cognition are demonstrated in OUD subjects after prolonged abstinence, but not in the subjects undergoing methadone treatment.Normalization in the composition of brain oscillations especially in the temporal region is induced and restored by methadone treatment in roughly 6 months in mean duration for OUDs having a mean opioid-use history of 10 years.We hope that the review provides valuable implications for clinical research and practice and paves a new insight into the future path to the identification of potential biomarkers and clinical outcome predictors in OUD in the domains of brain regions, functions, and behaviors.

In humans, intradermal administration of β-alanine (ALA) and bovine adrenal medulla peptide 8–22 (BAM8-22) evokes the sensation of itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express the receptors of these pruritogens, MRGPRD and MRGPRX1, respectively, and which cutaneous afferents these pruritogens activate in primate. In situ hybridization studies revealed that MRGPRD and MRGPRX1 are co-expressed in a subpopulation of TRPV1+ human DRG neurons. In electrophysiological recordings in nonhuman primates (Macaca nemestrina), subtypes of polymodal C-fiber nociceptors are preferentially activated by ALA and BAM8-22, with significant overlap. When pruritogens ALA, BAM8-22, and histamine, which activate different subclasses of C-fiber afferents, are administered in combination, human volunteers report itch and nociceptive sensations similar to those induced by a single pruritogen. Our results provide evidence for differences in pruriceptive processing between primates and rodents, and do not support the spatial contrast theory of coding of itch and pain.

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.

Chronic and recurrent opiate use injuries brain tissue and cause serious pathophysiological changes in hemodynamic and subsequent inflammatory responses. Prefrontal cortex (PFC) has been implicated in drug addiction. However, the mechanism underlying systems-level neuroadaptations in PFC during abstinence has not been fully characterized. The objective of our study was to determine what neural oscillatory activity contributes to the chronic effect of opiate exposure and whether the activity could be coupled to neurovascular information in the PFC. We employed resting-state functional connectivity to explore alterations in 8 patients with heroin dependency who stayed abstinent (>3 months; HD) compared with 11 control subjects. A non-invasive neuroimaging strategy was applied to combine electrophysiological signals through electroencephalography (EEG) with hemodynamic signals through functional near-infrared spectroscopy (fNIRS). The electrophysiological signals indicate neural synchrony and the oscillatory activity, and the hemodynamic signals indicate blood oxygenation in small vessels in the PFC. A supervised machine learning method was used to obtain associations between EEG and fNIRS modalities to improve precision and localization. HD patients demonstrated desynchronized lower alpha rhythms and decreased connectivity in PFC networks. Asymmetric excitability and cerebrovascular injury were also observed. This pilot study suggests that cerebrovascular injury in PFC may result from chronic opiate intake.

Many patients with substance use disorders (SUDs) live in a stressful environment, and comorbidity is not uncommon. Understanding the neural mechanisms underlying heroin and nicotine dependences and their relationships to social cognition could facilitate behavioral therapy efficacy. We aimed to provide a translational approach that leads to identifying potential biomarkers for opioid use disorder (OUD) susceptibility during recovery. We examined the clinical characters and the relationships between theory of mind (ToM) and executive functions in three groups: heroin plus nicotine-dependent (HND) patients who had remained heroin abstinent ( months), nicotine-dependent (ND) subjects, and healthy controls (C). The domains included emotion recognition, inhibition, shifting, updating, access, and processing speed. Resting-state functional connectivity (rsFC), ToM task-induced functional connectivity, and brain networks were then explored among 21 matched subjects using functional near-infrared spectroscopy. HND enhanced the severities of anxiety, depression, and hyperactivity. Inhibition domain was impaired in both HND and ND. No impairment in domains of emotion recognition, access, and update was observed. HND demonstrated enhanced rsFC in the medial prefrontal cortex and orbitofrontal cortex (OFC) and decreased ToM-induced connectivity across the PFC. The right superior frontal gyrus in the OFC (oSFG; , , and ) was associated with working memory and emotion recognition in HND. Using a neuroimaging tool, these results supported the prominent reward-deficit-and-stress-surfeit hypothesis in SUDs, especially OUD, after protracted withdrawal. This may provide an insight in identifying potential biomarkers related to a dynamic environment.

In human, intradermal administration of β-alanine (ALA) and bovine adrenal medulla peptide 8-22 (BAM8-22) evokes the sensation of itch. Currently, it is unknown which human dorsal root ganglion (DRG) neurons express the receptors of these pruritogens, MRGPRD and MRGPRX1 respectively, and which cutaneous afferents these pruritogens activate in primate. In situ hybridization studies revealed that MRGPRD and MRGPRX1 are co-expressed in a subpopulation of TRPV1+ human DRG neurons. In electrophysiological recordings in nonhuman primates (Macaca nemestrina), subtypes of polymodal C-fiber nociceptors are preferentially activated by ALA and BAM8-22, with significant overlap. When pruritogens ALA, BAM8-22 and histamine, that activate different subclasses of C-fiber afferents, are administered in combination, human volunteers report itch and nociceptive sensations similar to those induced by a single pruritogen. Our results provide evidence for differences in pruriceptive processing between primates and rodents, and do not support the spatial contrast theory of coding of itch and pain.

Background Ficin, a cysteine protease derived from fig‐tree latex, has been reported to elicit itch and nociceptive sensations, though quantitative sensory studies are lacking. Cowhage containing the pruritic cysteine Mucunain, on the contrary, has been widely studied as activating polymodal nociceptors and eliciting a histamine‐independent itch. Objectives We tested whether ficin in heat‐inactivated cowhage spicules would elicit itch and nociceptive sensations in humans, and analogous behaviours in mice, which are similar to those evoked by native cowhage, and whether these behaviours in mice were dose‐dependent when ficin was injected intradermally. Methods Human volunteers rated the magnitude of itch and nociceptive sensations evoked by either native cowhage spicules or heat‐inactivated spicules soaked in 1, 10 or 100 mg/mL ficin (0.03, 0.3 and 3 ng of ficin in spicule tip), applied to forearm. In mice, itch‐like scratching and nociceptive‐like wiping were recorded in response to either native cowhage, to heat‐inactivated spicules that were either inactive or contained 100 mg/mL ficin, or to intradermal injections of 1.25, 2.5 or 5 μg/ 5 μL, each treatment applied to the cheek. Results The dose of 100 mg/mL ficin in spicules evoked comparable magnitudes of itch, nociceptive sensations and areas of cutaneous dysesthesia as native cowhage in humans and comparable itch‐like scratching and pain‐like wiping behaviours in mice. But to elicit similar behaviours when injected intradermally in mice a greater amount of ficin (1.25 μg) was required. Conclusion Spicule delivery or intradermal injection of ficin elicits behaviours in mice that model itch and nociceptive sensations in humans, suggesting that ficin may be useful in translating mechanistic research on the neural mechanisms of pruritic and nociceptive effects of cysteine proteases between the two species.

Functional near-infrared spectroscopy (fNIRS) has emerged as a highly promising brain mapping technique that enables continuously and noninvasively monitoring the hemodynamic responses in the human brain. In this study, fNIRS was utilized to identify the different brain activation patterns between pathological gamblers (PGs) and healthy controls (HCs). Specifically, we examined the hemodynamic changes in the prefrontal cortex using fNIRS recordings during the completion of executive function and decision-making tasks for both PGs and HCs. Our mapping results revealed that PGs and HCs exhibited notable differences in the hemodynamic responses and brain activation patterns across the prefrontal region.