Abnormal hippocampal substructure volume in insomnia disorder.

To date, our understanding of the role of abnormal hippocampal volume in imaging studies of insomnia disorders (ID) has remained in apparent contradiction. Given that hippocampal function can be mapped to anatomically defined substructures, the hippocampal substructure volume can be examined in detail at present. In this study, we examined the volumes of hippocampal substructures between IDs and healthy controls (HC) to accurately find hippocampal markers of ID. First, we used the automated hippocampal substructure module in FreeSurfer6.0 to inspect T1-weighted magnetic resonance images between 22 IDs and 30 HC. Then, 12 hippocampal substructures were computed. Volumetric assessment was performed at the hippocampal substructure level between groups. Our study revealed significant reduced volume of the bilateral fimbria in IDs compared with HC (p < 0.05/12, Bonferroni corrected), although there was no difference in the total volume of hippocampus. In addition, the correlation analysis showed that the total hippocampal volume of the left hemisphere was negatively correlated with Pittsburgh Sleep Quality Index (PSQI) scores. With regard to hippocampal substructure results, negative correlations were detected between bilateral fimbria volume and clinical variables (i.e., PSQI, SDS, and SAS) in all subjects. Taken together, we revealed marked differences in the volume of the hippocampal substructure between IDs and HC, which provided a more accurate structural imaging marker for the pathological of ID.

Reduced midbrain functional connectivity and recovery in abstinent heroin users.

Dopaminergic pathways from the midbrain to striatum as well as cortex are involved in addiction. However, the alternations of these pathways and whether the recoveries of aberrant circuits would be detected after prolonged abstinence in heroin users are rarely known. The resting-state functional connectivity (RSFC) patterns of midbrain (i.e., the ventral tegmental area (VTA) and substantia nigra (SN)) were compared between 40 abstinent heroin users with opioid use disorder (HUs) and 35 healthy controls (HCs). Then, we tested the functional recovery hypothesis by both cross-sectional and longitudinal design. For cross-sectional design, HUs were separated into short-term abstainers (STs) (3-15 days) and long-term abstainers (LTs) (>15 days). With regard to longitudinal design, 22 subjects among HUs were followed up for 10 months. A sandwich estimator method was used to analyze the differences between baseline HUs and follow-up HUs. HUs showed lower RSFC between midbrain and several cortical areas (medial orbitofrontal cortex (mOFC) and anterior cingulate cortex) compared with HCs. Besides, lower RSFC of VTA-right nucleus accumbens circuit as well as right SN- caudate circuit was also found in HUs. The enhanced RSFC value of VTA-left mOFC circuit was observed in LTs, compared with STs. Additionally, longitudinal design also revealed the increased RSFC values of the midbrain with frontal cortex after 10 months prolonged abstinence. We revealed abnormal functional organizations of midbrain-striato and midbrain-cortical circuits in HUs. More importantly, partially recovery of these dysfunctions can be found after long-term abstinence.

Brain responses to drug cues predict craving changes in abstinent heroin users: A preliminary study.

BACKGROUND: Loss of control over drug intake occurring in drug addiction is believed to result from disruption of reward circuits, including reduced responsiveness to natural rewards (e.g., monetary, sex) and heightened responsiveness to drug reward. Yet few studies have assessed reward deficiency and related brain responses in abstinent heroin users with opioid use disorder, and less is known whether the brain responses can predict cue-induced craving changes following by prolonged abstinence. METHOD: 31 heroin users (age: 44.13±7.68 years, male: 18 (58%), duration of abstinence: 85.2 ± 52.5 days) were enrolled at a mandatory detoxification center. By employing a cue-reactivity paradigm including three types of cues (drug, sexual, neutral), brain regional activations and circuit-level functional coupling were extracted. Among the 31 heroin users, 15 were followed up longitudinally to assess cue induced craving changes in the ensuing 6 months. RESULTS: One way analysis of variance results showed that heroin users have differential brain activations to the three cues (neutral, drug and sexual) in the left dorsolateral prefrontal cortex (DLPFC), insula, orbiotofrontal cortex (OFC) and the bilateral thalamus. Drug cue induced greater activations in left DLPFC, insula and OFC compared to sexual cue. The psychophysiological interactions (PPI) analysis revealed negative couplings of the left DLPFC and the left OFC, bilateral thalamus, putamen in heroin users during drug cue exposure. In the 6-month follow-up study, both drug cue induced activation of the left DLPFC and the functional coupling of the left DLPFC-bilateral thalamus at baseline was correlated with craving reductions, which were not found for sexual cues. CONCLUSION: Our preliminary study provided novel evidence for the reward deficiency theory of opioid use disorder. Our findings also have clinical implications, as drug cue induced activation of the left DLPFC and functional coupling of left DLPFC-bilateral thalamus may be potential neuroimaging markers for craving changes during prolonged abstinence. Evidently, the findings in the current preliminary study should be confirmed by large sample size in the future.

Disrupted frontostriatal connectivity in primary insomnia: a DTI study.

Dysfunction of the sleep-wake transition is considered to be associated with the pathology of patients with primary insomnia (PI). Previous animal study had reported that brain circuits between the striatum and cortex can regulate sleep-wake transitions. So far, few studies have systematically explored the structural connectivity of the striatum-centered circuits and their potential roles in patients with PI. In this study, we chosen the striatum as the seed and 10 priori target regions as masks to assess the structural connectivity by using seed-based classification with a diffusion tensor imaging (DTI) probabilistic tractography method. Track strengths of the striatum-centered circuits were compared between 22 patients with PI (41.27 ± 9.21 years) and 30 healthy controls (HC) (35.2 ± 8.14 years). Pittsburgh Sleep Quality Index (PSQI) was used to measure the sleep quality in all participants. Lower track strengths (left striatum- anterior cingulate cortex (ACC), left striatum- dorsal anterior cingulate cortex (dACC), left striatum-Hippocampus, and right striatum-Hippocampus) were observed in patients with PI compared to HC. Additionally, the lower track strengths of brain circuits mentioned above were negatively correlated with PSQI. Taken together, our findings revealed the lower tract strength of frontostriatal circuits in patients with PI and HC, which provided the implications of the system-level structural connections of frontostriatal circuits in the pathology of PI. We suggested that the track strengths of the frontostriatal circuits calculated from DTI can be the potential neuroimaging biomarkers of the sleep quality in patients with PI.

Impulsivity in heroin-dependent individuals: structural and functional abnormalities within frontostriatal circuits.

High levels of impulsivity are a risk factor for the initiation of heroin use and a core behavioral characteristic of heroin dependence. Impulsivity also contributes to the maintenance of drug use and hinders effective therapy. Here we sought to identify neuroimaging markers of impulsivity in heroin-dependent individuals (HDI), with a focus on the nucleus accumbens (NAc), a key region implicated in impulsivity and drug addiction generally. Volume and resting-state functional connectivity (RSFC) differences of the bilateral NAc were investigated between 21 HDI and 21 age-, gender-, nicotine-, alcohol-matched healthy controls (HC). The neuroimaging results were then correlated with the Barratt Impulsivity Scales (BIS-11). Higher motor impulsivity (t = 2.347, p = 0.0253) and larger right NAc volume (F (1,38) = 4.719, p = 0.036) was observed in HDI. The right NAc volume was positively correlated with BIS total (r = 0.6196, p = 0.0239) /motor (r = 0.5921, p = 0.0330) scores in HC and BIS motor (r = 0.5145, p = 0.0170) score in HDI. A negative correlation was found between RSFC of the right NAc-bilateral superior frontal gyrus (SFG) and motor impulsivity in HDI (left: r=-0.6537, p = 0.0013; right: r=-0.6167, p = 0.0029) and HC (left: r=-0.6490,p = 0.0164; right: r=-0.6993, p = 0.0078). We aimed to reveal novel multimodality neuroimaging biomarkers of the higher impulsivity in HDI by focusing on the NAc and corresponding functional circuits. Higher motor impulsivity was observed in HDI. Furthermore, the volume of the right NAc and the RSFC strength of right NAc-SFG could be neuroimaging biomarkers for the severity of impulsivity in HDI. These potential biomarkers could be a target for novel treatments in HDI.

Reduced thalamic resting-state functional connectivity and impaired cognition in acute abstinent heroin users.

As a critical component of cortico-striato-thalamo-cortical loop in addiction, our understanding of the thalamus in impaired cognition of heroin users (HU) has been limited. Due to the complex thalamic connection with cortical and subcortical regions, thalamus was divided into prefrontal (PFC), occipital (OC), premotor, primary motor, sensory, temporal, and posterior parietal association subregions according to white matter tractography. We adopted seven subregions of bilateral thalamus as regions of interest to systematically study the implications of distinct thalamic nuclei in acute abstinent HU. The volume and resting-state functional connectivity (RSFC) differences of the thalamus were investigated between age-, gender-, and alcohol-matched 37 HU and 33 healthy controls (HCs). Trail making test-A (TMT-A) was adopted to assess cognitive function deficits, which were then correlated with neuroimaging findings. Although no significant different volumes were found, HU group showed decreased RSFC between left PFC_thalamus and middle temporal gyrus as well as between left OC_thalamus and inferior frontal gyrus and supplementary motor area relative to HCs. Meanwhile, the higher TMT-A scores in HU were negatively correlated with PFC_thalamic RSFC with inferior temporal gyrus, fusiform, and precuneus. Craving scores were negatively correlated with OC_thalamic RSFC with accumbens, hippocampus, and insula. Opiate Withdrawal Scale scores were negatively correlated with left PFC/OC_thalamic RSFC with orbitofrontal cortex and medial PFC. We indicated two thalamus subregions separately involvement in cognitive control and craving to reveal the implications of thalamic subnucleus in pathology of acute abstinent HU.

Dysfunction of the NAc-mPFC circuit in insomnia disorder.

BACKGROUND: Insomnia disorder (ID) is a prevalent sleep disorder, which seriously affects people's daily life and was found to be associated with increased frequency of sleep stage shifts. Previous findings had revealed the critical role of the nucleus accumbens (NAc) in sleep-wake transition. However, the neuroimaging studies of the NAc in patients with ID have been rare. We hypothesized that structural and functional abnormalities of the NAc would be implicated in ID. METHODS: Twenty-six ID patients and 36 matched healthy controls (HC) were included in the current study. The volumes and corresponding resting-state functional connectivity (RSFC) of the bilateral NAc were compared between the two groups. The abnormal RSFC in ID were then correlated with Pittsburgh Sleep Quality Index (PSQI). RESULTS: Compared with HC, ID patients showed significantly increased volume of right NAc. Several brain regions showed increased RSFC with the NAc in ID patients, such as medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), caudate and putamen. Meanwhile, the occipital gyrus and temporal gyrus showed decreased RSFC with the NAc. Additionally, the increased RSFC strength between bilateral NAc and left mPFC was significant correlated with PSQI scores in ID patients. CONCLUSION: Dysfunctions of the NAc-mPFC circuit were found in ID patients, which were associated with sleep quality measured by PSQI. The two patterns of increase and decrease of RSFC in ID patients observed in our study may reflect the state of hyperarousal and potential impairment of cognitive function in the patients, respectively. It is hoped that our study focusing on NAc-mPFC circuits could provide new insights for the neural mechanisms of ID and potential novel therapeutic targets for treatment of ID patients.