Altered Functional Connectivity Research Articles

Stress, immune mechanisms, and mental illness: from etiology to treatment

It is now well-established that a strong relationship exists between psychiatric disorders and disturbances of immune mechanisms at different stages of life. Indeed, a derangement in the expression and function of specific immune elements may predispose and contribute to the development of different psychopathologic conditions and could also represent an important component that must be targeted by therapeutic intervention. The proposed symposium will summarize authoritatively the important recent advances on the immune mechanisms contributing to the etiology of psychiatric disorders, with a specific focus on the role of stress, and it will discuss if and how the effectiveness of therapeutic intervention may depend on the ability to regulate immune mechanisms that are altered under pathologic conditions. The symposium will unfold upon the discussion of preclinical and clinical studies addressing different aspects related to psychiatric disorders. Prof. A. Pillai (University of Texas, U.S.A.) will specifically discuss the roles of neuroinflammation and synapse loss in IFN-I signaling-mediated social deficits under chronic stress conditions. He will discuss how peripheral blockade of IFN-I signaling attenuated stress-induced neuroimmune alterations and social behavioral deficits and also the key role of complement component 3a receptor 1 (C3ar1) in these mechanisms. Along this line, Prof. M.A. Riva (University of Milan, Italy) will show how immune mechanisms and dysregulation of microglial function may contribute to the vulnerability to stress at different life stages, from adolescence to adulthood. Moreover, he will discuss how the normalization of some of these mechanisms following pharmacological intervention may contribute to therapeutic effectiveness in the treatment of different psychiatric disorders characterized, particularly in patients characterized by a higher inflammatory status. At the clinical level, Dr. G. Scaini (University of Texas, U.S.A.) will discuss the interplay between inflammation, stress, and mitochondria in bipolar disorder patients. She will highlight the significant correlation between alterations in mitochondrial proteins and inflammatory markers with a decrease in functional status and an increase in the severity of symptoms. Lastly, Prof. J. Felger (Emory Univ.) will discuss how depressed patients with increased inflammation show altered functional connectivity within the ventral striatum to ventromedial prefrontal cortex reward circuitry in relation to symptoms of anhedonia. These changes can be improved by pharmacological intervention aimed to increase dopamine levels suggesting that functional connectivity in reward circuitry may also serve as a modifiable imaging biomarker for the efficacy of pharmacological and/or behavioral interventions to reverse the impact of inflammation on the brain of depressed subjects.

Functional connectivity changes in infants with varying degrees of unilateral hearing loss.

It has been proved that unilateral hearing loss (UHL) can cause functional connectivity alterations in adults. However, the mechanism of the human brain coping with the challenge of unilateral hearing deprivation at very early developmental phases remains poorly understood. Here, we performed a resting-state functional near-infrared spectroscopy (fNIRS) study on 3- to 10-month-old infants with varying degrees of unilateral hearing loss to investigate the effect of unilateral auditory deprivation in infants. Using network-based statistics, increased functional connectivity was observed in single-sided deafness (SSD) compared with normal hearing infants, and the right middle temporal gyrus was the most involved nodes. In addition, changes in cortical function in infants were related to the degree of hearing loss, with significantly increased functional connectivity in infants with severe to profound unilateral hearing loss compared with the ones with mild to moderate. Moreover, more significant cortical functional recombination changes were found in right-SSD than in left-SSD infants. For the first time, our study provides evidence for the effects of unilateral hearing deprivation on the early cortical development of the human brain, which would also act as a reference for intervention decisions in children with unilateral hearing loss in clinical settings.

Functional and Structural Brain Abnormalities and Clinical Characteristics of Male Patients with Alcohol Dependence.

Even though many previous studies have reported structural or functional brain abnormalities in patients with alcohol dependence (ADPs), studies observing the structural and functional abnormalities associated with the clinical characteristics of ADPs utilizing a multimodal approach are still scarce. The aim of this study was to demonstrate structural and functional brain abnormalities and their association with the clinical characteristics of alcoholism in male ADPs. Fifteen healthy male controls (HCs) and 15 male ADPs who had been diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 5 criteria underwent T1-weighted imaging and resting-state functional magnetic resonance imaging (MRI) scans. The MRI data were postprocessed using statistical parametric mapping for structural analysis and CONN-fMRI functional connectivity (FC) tools for functional analysis. In comparison with male HCs, male ADPs were characterized by significantly reduced volumes of the white matter in the left globus pallidus (GP) (p-FDR < 0.05). This region affected the altered resting-state FC patterns in male ADPs. Interestingly, an abnormal FC in the precuneus and its positive correlation with the alcohol-use disorder identification test score were observed in ADPs (r = 0.546, p = 0.036). Based on the observations, it could be concluded that the GP serves as a neural marker that impacts abnormal functional networks in men with alcohol dependence. These findings have important clinical implications as they provide insights into the neural mechanism underlying the anatomical, functional, and clinical features of alcoholism.

Cognitive function in primary and secondary progressive multiple sclerosis: a multiparametric MRI study.

The differences in cognitive function between primary progressive (PP) and secondary progressive (SP) multiple sclerosis (MS) remain unclear. We compared cognitive performance between PPMS and SPMS, and explored the structural and functional MRI correlates of their cognitive functions. Seventy-five healthy controls and 183 MS patients (60 PPMS and 123 SPMS) underwent 3.0T MRI. MS patients were administered the Brief Repeatable Battery of Neuropsychological Tests; cognitive domain z-scores were calculated and then averaged to obtain a measure of global cognition. Using hierarchical linear regression analysis, the contribution of lesion volumes, normalized brain volumes, white matter fractional anisotropy (FA) and mean diffusivity abnormalities, and resting state (RS) functional connectivity (FC) alterations to global cognition in PPMS and SPMS was investigated. PPMS and SPMS had similar z-scores in all investigated cognitive domains. Poor global cognitive function resulted associated with decreased FA of the medial lemniscus (ΔR2 =0.11; p=0.011) and lower normalized gray matter volume (ΔR2 =0.29; p<0.001) in PPMS, and with decreased FA of the fornix (ΔR2 =0.35; p<0.001) and lower normalized white matter volume (ΔR2 =0.05; p=0.034) in SPMS. PPMS and SPMS had similar neuropsychological performance. Cognitive dysfunction in PPMS and SPMS was related to distinct patterns of structural MRI abnormalities and involvement of different white matter tracts, while RS FC alterations did not contribute to explain their global cognitive functioning.

Altered amygdala functional connectivity after real-time functional MRI emotion self-regulation training.

Real-time functional MRI neurofeedback (rtfMRI-NF) is a noninvasive technique that extracts concurrent brain states and provides feedback to subjects in an online method. Our study aims to investigate the effect of rtfMRI-NF on amygdala-based emotion self-regulation by analyzing resting-state functional connectivity. We conducted a task experiment to train subjects in self-regulating amygdala activity in response to emotional stimuli. Twenty subjects were divided into two groups. The up-regulate group (URG) viewed positive stimulus, while the down-regulate group (DRG) viewed negative stimulus. The rtfMRI-NF experiment paradigm consisted of three conditions. The URG's percent amplitude fluctuation (PerAF) scores are significant, indicating that positive emotions may be a partial side effect, with increased activity in the left hemisphere. Resting-state functional connectivity was analyzed via a paired-sample t-test before and after neurofeedback training. Brain network properties and functional connectivity analysis showed a significant difference between the default mode network (DMN) and the brain region associated with the limbic system. These results reveal to some extent the mechanism of neurofeedback training to improve individuals' emotional regulate regulation ability. Our study has shown that rtfMRI-neurofeedback training can effectively enhance the ability to voluntarily control brain responses. Furthermore, the results of the functional analysis have revealed distinct changes in the amygdala functional connectivity circuits following rtfMRI-neurofeedback training. These findings may suggest the potential clinical applications of rtfMRI-neurofeedback as a new therapy for emotionally related mental disorders.

Alterations in learning-related cortical activation and functional connectivity by high-definition transcranial direct current stimulation after stroke: an fNIRS study.

Motor learning is a key component of stroke neurorehabilitation. High-definition transcranial direct current stimulation (HD-tDCS) was recently developed as a tDCS technique that increases the accuracy of current delivery to the brain using arrays of small electrodes. The purpose of this study was to investigate whether HD-tDCS alters learning-related cortical activation and functional connectivity in stroke patients using functional near-infrared spectroscopy (fNIRS). Using a sham-controlled crossover study design, 16 chronic stroke patients were randomly assigned to one of two intervention conditions. Both groups performed the sequential finger tapping task (SFTT) on five consecutive days, either with (a) real HD-tDCS or (b) with sham HD-tDCS. HD-tDCS (1 mA for 20 min, 4 × 1) was administered to C3 or C4 (according to lesion side). fNIRS signals were measured during the SFTT with the affected hand before (baseline) and after each intervention using fNIRS measurement system. Cortical activation and functional connectivity of NIRS signals were analyzed using a statistical parametric mapping open-source software package (NIRS-SPM), OptoNet II®. In the real HD-tDCS condition, oxyHb concentration increased significantly in the ipsilesional primary motor cortex (M1). Connectivity between the ipsilesional M1 and the premotor cortex (PM) was noticeably strengthened after real HD-tDCS compared with baseline. Motor performance also significantly improved, as shown in response time during the SFTT. In the sham HD-tDCS condition, functional connectivity between contralesional M1 and sensory cortex was enhanced compared with baseline. There was tendency toward improvement in SFTT response time, but without significance. The results of this study indicated that HD-tDCS could modulate learning-related cortical activity and functional connectivity within motor networks to enhance motor learning performance. HD-tDCS can be used as an additional tool for enhancing motor learning during hand rehabilitation for chronic stroke patients.

ID: 208214 Comparison of Amplitude and Phase Synchronization in Detecting Functional Connectivity Alterations in Mesial Temporal Sclerosis

Temporal lobe epilepsy (TLE) is the most common form of refractory focal epilepsy1,2. Mesial temporal sclerosis (MTS) is a subtype of TLE and can cause severe complications3. Resting-state fMRI (rsfMRI) has been used to detect alterations in functional connectivity (FC) in patients with MTS4–6. Amplitude synchronization (AS) via seed-to-voxel analysis is a method used to detect FC from rsfMRI7,8. Phase synchronization (PS) is a technique used primarily with EEG to detect FC but has not been widely used in rsfMRI analysis9,10. In this study, we aimed to compare phase and amplitude synchronization in detecting temporal lobe FC alterations in MTS patients.

Resting‐State Connectivity Changes in Older Adults with Sleep Disturbance

AbstractBackgroundSleep and related disorders could lead to changes in various brain network connectivities, but little is known about the role of Aβ burden—a key Alzheimer’s disease (AD) biomarker—in the relationship between sleep disturbance and altered functional connectivity in older adults. This study examined the association between sleep disturbance, Aβ positivity, and with‐in and between resting‐state functional connectivity networks using a large‐scale dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI).MethodSample was consisted of 413 individuals (mean age 76.56±7.20; 57.5% cognitively normal, 30.3% mild cognitive impairment, and 12.1% AD) who had completed sleep measures (Neuropsychiatric Inventory), CSF‐Aβ42 data, and resting‐state fMRI scans at baseline. Functional connectivity within Salience (SN), Default Mode (DMN) and Frontal Parietal networks (FPN) were compared between participants with sleep disturbance versus without sleep disturbance. The interaction between Aβ positivity and sleep disturbance were evaluated controlling for age, diagnosis status, gender, sedatives and hypnotics use, and hypertension.ResultSleep disturbance was associated with reduced connectivity in the SN (β = 0.04, P = 0.006) but not with DMN or FPN. Additionally, sleep disturbance interacted significantly with Aβ positivity in altered with‐in connectivity of SN (β = 0.10, P = 0.003), DMN (β = 0.07, P = 0.0048), and FPN (β = 0.09, P = 0.03) networks.ConclusionSleep disturbance may lead to altered connectivity in the SN and further change various within and between functional networks in the presence of amyloid burden.

ID: 209374 Temporal Lobe Epilepsy Patients Demonstrate Altered Age-Related Segregation Patterns in Brainstem Arousal Networks

Recurrent consciousness-impairing seizures are associated with widespread brain network changes and disabling neurocognitive deficits in patients with temporal lobe epilepsy (TLE) (Englot et al, 2020). We have shown altered functional connectivity in the brainstem ascending reticular acting system (ARAS) found in TLE patients (Englot et al, 2017) that may correlate with impairments in cognitive testing and may improve after surgical treatment (González et al, 2020). Studies of the ARAS network in control subjects have shown a significant age-related decrease in a within-network connectivity metric called segregation. Furthermore, patients with TLE have been shown to have clinical and radiological accelerated age-related changes. Thus, we sought to investigate any possible age-related ARAS network changes in TLE. Understanding how the ARAS is impacted may offer insight into how neurostimulation may improve its network dynamics.

ID: 195863 Functional Connectivity Alterations in Seizure Onset and Spread Regions in Patients With Non-Lesional Epilepsy

Abnormal neural activity may facilitate seizure spread and symptom manifestation in epilepsy1. Epilepsy is defined as non-lesional (NLE) when a structural lesion cannot be localized via standard neuroimaging2. NLE is known to have worse response to surgery compared to epilepsy with detected lesions3,4. We examined whether patient resting-state fMRI (rsfMRI) can detect functional connectivity (FC) metric alterations in the onset zone (OZ) and early spread zone (ESZ) in NLE. These metrics consist of amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF), measures of intensity in fMRI-relevant frequency bands; regional homogeneity (ReHo), a measure of local synchronicity; degree of centrality (DoC), a measure of voxel connectivity; and voxel-mirrored homotopic connectivity (VMHC), a measure of synchronicity with the analogous voxel in the contralateral hemisphere5-11. We aimed to see whether noninvasive imaging techniques can uncover alterations in seizure-related regions.

Non-reversibility outperforms functional connectivity in characterisation of brain states in MEG data

Characterising brain states during tasks is common practice for many neuroscientific experiments using electrophysiological modalities such as electroencephalography (EEG) and magnetoencephalography (MEG). Brain states are often described in terms of oscillatory power and correlated brain activity, i.e. functional connectivity. It is, however, not unusual to observe weak task induced functional connectivity alterations in the presence of strong task induced power modulations using classical time-frequency representation of the data. Here, we propose that non-reversibility, or the temporal asymmetry in functional interactions, may be more sensitive to characterise task induced brain states than functional connectivity. As a second step, we explore causal mechanisms of non-reversibility in MEG data using whole brain computational models. We include working memory, motor, language tasks and resting-state data from participants of the Human Connectome Project (HCP). Non-reversibility is derived from the lagged amplitude envelope correlation (LAEC), and is based on asymmetry of the forward and reversed cross-correlations of the amplitude envelopes. Using random forests, we find that non-reversibility outperforms functional connectivity in the identification of task induced brain states. Non-reversibility shows especially better sensitivity to capture bottom-up gamma induced brain states across all tasks, but also alpha band associated brain states. Using whole brain computational models we find that asymmetry in the effective connectivity and axonal conduction delays play a major role in shaping non-reversibility across the brain. Our work paves the way for better sensitivity in characterising brain states during both bottom-up as well as top-down modulation in future neuroscientific experiments.

Disruption of locus coeruleus-related functional networks in Parkinson’s disease

Locus coeruleus (LC) is severely affected in Parkinson’s Disease (PD). However, alterations in LC-related resting-state networks (RSNs) in PD remain unclear. We used resting-state functional MRI to investigate the alterations in functional connectivity (FC) of LC-related RSNs and the associations between RSNs changes and clinical features in idiopathic rapid eye movement sleep behavior disorder (iRBD) and PD patients with (PDRBD+) and without RBD (PDRBD−). There was a similarly disrupted FC pattern of LC-related RSNs in iRBD and PDRBD+ patients, whereas LC-related RSNs were less damaged in PDRBD− patients than that in patients with iRBD and PDRBD+. The FC of LC-related RSNs correlated with cognition and duration in iRBD, depression in PDRBD−, and cognition and severity of RBD in patients with PDRBD+. Our findings demonstrate that LC-related RSNs are significantly disrupted in the prodromal stage of α-synucleinopathies and proposed body-first PD (PDRBD+), but are less affected in brain-first PD (PDRBD−).

Altered functional connectivity of the ascending reticular activating system in obstructive sleep apnea

Repeated arousals during sleep in obstructive sleep apnea (OSA) may lead to altered functional connectivity (FC) of the ascending reticular activating system (ARAS). We evaluated resting-state FC between eight ARAS nuclei and 105 cortical/subcortical regions in OSA patients and healthy controls. Fifty patients with moderate to severe OSA and 20 controls underwent overnight polysomnography and resting-state functional magnetic resonance imaging. Seed-to-voxel analysis of ARAS–cortex FC was compared between OSA patients and controls. The ARAS nuclei included the locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), and ventral tegmental area (VTA). FC values of three ARAS nuclei (the LC, LDTg, and VTA) significantly differed between the groups. FC of the LC with the precuneus, posterior cingulate gyrus, and right lateral occipital cortex (LOC) was stronger in OSA patients than controls. FC between the LDTg and right LOC was stronger in OSA patients than controls, but FC between the VTA and right LOC was weaker. Average LC–cortex FC values positively correlated with the arousal, apnea, and apnea–hypopnea index in OSA patients. Alterations in ARAS–cortex FC were observed in OSA patients. The strength of LC–cortex noradrenergic FC was related to arousal or OSA severity in patients.

Altered Functional Connectivity of the Nucleus Accumbens and Amygdala in Cyber Addiction: A Resting State Functional Magnetic Resonance Imaging Study

Cyber addiction, which is more vulnerable in adolescents, is defined as the excessive use of computers and the Internet that causes serious psychological, social, and physical problems. In this study, we investigated the resting-state functional connectivity (rsFC) in adolescents with cyber addiction. We collected and analyzed resting-state functional neuroimaging data of 20 patients with cyber addiction, aged 13-18 years, and 27 healthy controls. Based on previous studies, the seed regions included the dorsolateral prefrontal cortex, medial orbitofrontal cortex, lateral orbitofrontal cortex, dorsal anterior cingulate cortex, insula, hippocampus, amygdala, nucleus accumbens, and the ventral tegmental area. Seed-to-voxel analyses were performed to investigate the differences between patients and healthy controls. A correlation analysis between rsFC and cyber addiction severity was also performed. Patients with cyber addiction showed the following characteristics: increased positive rsFC between the left insular-right middle temporal gyrus; increased positive rsFC between the right hippocampus-right precentral gyrus; increased positive rsFC between the right amygdala-right precentral gyrus and right parietal operculum cortex; increased negative rsFC between the left nucleus accumbens-right cerebellum crus II and right cerebellum VI. Adolescents with cyber addiction show altered functional connectivity during the resting state. The findings of this study may help us better understand the neuropathology of cyber addiction in adolescents.

0510 Altered functional connectivity of the ascending reticular activating system in obstructive sleep apnea

Abstract Introduction Recurrent arousals in obstructive sleep apnea (OSA) may lead to alteration in functional connection involving in the ascending reticular activating system (ARAS). We aimed to evaluate resting-state functional connectivity (FC) between eight ARAS nuclei and 105 cortical/subcortical regions in OSA patients and matched controls. Methods Total of 50 patients with moderate to severe OSA and 20 controls without OSA underwent overnight polysomnography (PSG) and resting-state functional magnetic resonance imaging in the following morning. Seed to voxel analysis of ARAS-cortical FC was compared between the patients and controls. The ARAS nuclei included dorsal and median raphe nucleus, locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), pedunculopontine tegmental nucleus, pontine nucleus oralis, parabrachial complex, and ventral tegmental area (VTA). Correlations between average FC values of significant clusters and PSG parameters were calculated in the patients. Results FC values in the three of the ARAS nuclei (LC, LDTg, and VTA) were significantly different between the group. The FC value between the LC and the precuneus cortex, posterior cingulate gyrus, and right lateral occipital cortex (LOC) was increased in OSA patients compared to the controls. The FC value between the LDTg and right LOC was enhanced, but the FC one between the VTA and right LOC was reduced in the patients. The average LC-cortical FC values positively correlated with the arousal index(r=0.282, p=0.047), apnea index(r=0.325, p=0.021), or apnea-hypopnea index (r=0.302, p=0.033) in OSA patients. Conclusion The results of this study support alteration in ARAS-cortical FC in OSA patients. Degree of the noradrenergic LC-cortical FC may be related to arousal or OSA severity in the patients. Support (if any)

Multi-Site MRI Data Harmonization with an Adversarial Learning Approach: Implementation to the Study of Brain Connectivity in Autism Spectrum Disorders

Magnetic resonance imaging (MRI) nowadays plays an important role in the identification of brain underpinnings in a wide range of neuropsychiatric disorders, including Autism Spectrum Disorders (ASD). Characterizing the hallmarks in these pathologies is not a straightforward task and machine learning (ML) is certainly one of the most promising tools for addressing complex and non-linear problems. ML algorithms and, in particular, deep neural networks (DNNs), need large datasets in order to be properly trained and thus ensure generalization capabilities on new data. Large datasets can be obtained by collecting images from different centers, thus bringing unavoidable biases in the analysis due to differences in hardware and scanning protocols between different centers. In this work, we dealt with the issue of multicenter MRI data harmonization by comparing two different approaches: the analytical ComBat-GAM procedure, whose effectiveness is already documented in the literature, and an originally developed site-adversarial deep neural network (ad-DNN). The latter aims to perform a classification task while simultaneously searching for site-relevant patterns in order to make predictions free from site-related biases. As a case study, we implemented DNN and ad-DNN classifiers to distinguish subjects with ASD with respect to typical developing controls based on functional connectivity measures derived from data of the multicenter ABIDE collection. The classification performance of the proposed ad-DNN, measured in terms of the area under the ROC curve (AUC), achieved the value of AUC = 0.70±0.03, which is comparable to that obtained by a DNN on data harmonized according to the analytical procedure (AUC = 0.71±0.01). The relevant functional connectivity alterations identified by both procedures showed an agreement between each other and with the patterns of neuroanatomical alterations previously detected in the same cohort of subjects.

Systems-level analysis of local field potentials reveals differential effects of lysergic acid diethylamide and ketamine on neuronal activity and functional connectivity.

Psychedelic substances have in recent years attracted considerable interest as potential treatments for several psychiatric conditions, including depression, anxiety, and addiction. Imaging studies in humans point to a number of possible mechanisms underlying the acute effects of psychedelics, including changes in neuronal firing rates and excitability as well as alterations in functional connectivity between various brain nodes. In addition, animal studies using invasive recordings, have suggested synchronous high-frequency oscillations involving several brain regions as another key feature of the psychedelic brain state. To better understand how the imaging data might be related to high-resolution electrophysiological measurements, we have here analyzed the aperiodic part of the local field potential (LFP) in rodents treated with a classic psychedelic (LSD) or a dissociative anesthetic (ketamine). In addition, functional connectivity, as quantified by mutual information measures in the LFP time series, has been assessed with in and between different structures. Our data suggest that the altered brain states of LSD and ketamine are caused by different underlying mechanisms, where LFP power shifts indicate increased neuronal activity but reduced connectivity following ketamine, while LSD also leads to reduced connectivity but without an accompanying change in LFP broadband power.

Identifying reproducible resting state networks and functional connectivity alterations following chronic restraint stress in anaesthetized rats.

Resting-state functional MRI (rs-fMRI) in rodent models have the potential to bridge invasive experiments and observational human studies, increasing our understanding of functional alterations in the brains of patients with depression. A major limitation in current rodent rs-fMRI studies is that there has been no consensus on healthy baseline resting-state networks (RSNs) that are reproducible in rodents. Therefore, the present study aimed to construct reproducible RSNs in a large dataset of healthy rats and then evaluate functional connectivity changes within and between these RSNs following a chronic restraint stress (CRS) model within the same animals. A combined MRI dataset of 109 Sprague Dawley rats at baseline and after two weeks of CRS, collected during four separate experiments conducted by our lab in 2019 and 2020, was re-analysed. The mICA and gRAICAR toolbox were first applied to detect optimal and reproducible ICA components and then a hierarchical clustering algorithm (FSLNets) was applied to construct reproducible RSNs. Ridge-regularized partial correlation (FSLNets) was used to evaluate the changes in the direct connection between and within identified networks in the same animals following CRS. Four large-scale networks in anesthetised rats were identified: the DMN-like, spatial attention-limbic, corpus striatum, and autonomic network, which are homologous across species. CRS decreased the anticorrelation between DMN-like and autonomic network. CRS decreased the correlation between amygdala and a functional complex (nucleus accumbens and ventral pallidum) in the right hemisphere within the corpus striatum network. However, a high individual variability in the functional connectivity before and after CRS within RSNs was observed. The functional connectivity changes detected in rodents following CRS differ from reported functional connectivity alterations in patients with depression. A simple interpretation of this difference is that the rodent response to CRS does not reflect the complexity of depression as it is experienced by humans. Nonetheless, the high inter-subject variability of functional connectivity within networks suggests that rats demonstrate different neural phenotypes, like humans. Therefore, future efforts in classifying neural phenotypes in rodents might improve the sensitivity and translational impact of models used to address aetiology and treatment of psychiatric conditions including depression.

Functional connectivity alterations in reward-related circuits associated with non-suicidal self-injury behaviors in drug-naïve adolescents with depression

Non-suicidal self-injury (NSSI) behaviors are a major public health concern among adolescents with depression. Such behaviors may be associated with the reward system. However, the underlying mechanism in patients with depression and NSSI still remains unclear. A total of 56 drug-naïve adolescents with depression, including 23 patients with NSSI (the NSSI group) and 33 patients without NSSI (the nNSSI group), and 25 healthy controls (HCs) were recruited in this study. Seed-based functional connectivity (FC) was used to explore the NSSI-related FC alterations in the reward circuit. Correlation analysis was conducted between the altered FCs and clinical data. Compared with the nNSSI group, the NSSI group showed greater FC between left nucleus accumbens (NAcc) and right lingual gyrus and between right putamen accumbens and right angular gyrus (ANG). The NSSI group also had declined FC between right NAcc and left inferior cerebellum, between left cingulate gyrus (CG) and right ANG, between left CG and left middle temporal gyrus (MTG), and between right CG and bilateral MTG (voxel-wise p < 0.01, cluster-wise p < 0.05, Gaussian random field correction). The FC between right NAcc and left inferior cerebellum was found positively correlated with the score of addictive features of NSSI (r = 0.427, p = 0.042). Our findings indicated that the regions in the reward circuit with NSSI-related FC alterations included bilateral NAcc, right putamen and bilateral CG, which may provide new evidence on the neural mechanisms of NSSI behaviors in adolescents with depression.

Neural correlates of decreased impulsivity during delay discounting task after laparoscopic sleeve gastrectomy.

The goal of this study was to investigate laparoscopic sleeve gastrectomy (LSG)-induced changes in choice impulsivity and the neural correlates in individuals with obesity (OB). The study employed functional magnetic resonance imaging with a delay discounting task in 29 OB tested before and 1 month after LSG. Thirty participants with normal weight matched to OB with gender and age were recruited as the control group and underwent an identical functional magnetic resonance imaging scan. Alterations in activation and functional connectivity between pre- and post-LSG were investigated and compared with participants with normal weight. OB exhibited significantly reduced discounting rate after LSG. During the delay discounting task, hyperactivation in dorsolateral prefrontal cortex, right caudate, and dorsomedial prefrontal cortex decreased in OB after LSG. LSG additionally engaged compensatory effects through increased activation in bilateral posterior insula and functional connectivity between caudate and dorsomedial prefrontal cortex. Those changes were associated with decreased discounting rate and BMI as well as improved eating behaviors. These findings indicate that decreased choice impulsivity following LSG was associated with the changes in regions involved in executive control, reward evaluation, interoception, and prospection. This study may provide neurophysiological support for the development of nonoperative treatments such as brain stimulation for individuals with obesity and overweight.