Seed-based Resting-state Functional Connectivity Research Articles

Aberrant Functional Connectivity of Basal Forebrain Subregions with Cholinergic System in Short-term and Chronic Insomnia Disorder

BackgroundTo systematically investigate structural and functional abnormalities in subregions of the basal forebrain (BF) using structural and resting-state fMRI, and to examine their clinical relevance in short-term and chronic insomnia disorder (ID). MethodsThirty-four patients with short-term ID, 41 patients with chronic ID, and 46 healthy controls (HCs) were recruited. Grey matter volume and seed-based resting-state functional connectivity (RSFC) in each BF subregion (Ch1,2,3 and 4) were computed and compared among the three groups. Spearman correlation was used to estimate the relationships between MRI-based alterations and clinical variables. ResultsThe short-term group exhibited lower RSFC with the bilateral striatum and bilateral Ch_4 than HCs and the chronic group. In the left Ch_4, subjects in the chronic group exhibited lower RSFC with the left middle cingulate cortex than HCs and the short-term group. The short-term group exhibited lower RSFC with the left parahippocampal gyrus (PHG) than HCs and the chronic group. The chronic group exhibited the highest RSFC with the left middle frontal gyrus (MFG), followed by HCs and the short-term group. In the right Ch_4, the chronic group exhibited the lowest RSFC with the right superior temporal gyrus, followed by HCs and the short-term group. Moreover, in the short-term group, negative correlations were found between the left Ch_4 and left MFG RSFC and Epworth Sleepiness Scale scores. ConclusionsThese findings suggest that the Ch_4 may be a key node for establishing diagnostic and categorical biomarkers of ID, which could be useful in developing more effective treatment strategies for insomnia.

Long-lasting connectivity changes induced by intensive first-person shooter gaming.

Action videogames have been shown to induce modifications in perceptual and cognitive systems, as well as in brain structure and function. Nevertheless, whether such changes are correlated with brain functional connectivity modifications outlasting the training period is not known. Functional magnetic resonance imaging (fMRI) was used in order to quantify acute and long-lasting connectivity changes following a sustained gaming experience on a first-person shooter (FPS) game. Thirty-five healthy participants were assigned to either a gaming or a control group prior to the acquisition of resting state fMRI data and a comprehensive cognitive assessment at baseline (T0), post-gaming (T1) and at a 3months' follow-up (T2). Seed-based resting-state functional connectivity (rs-FC) analysis revealed a significant greater connectivity between left thalamus and left parahippocampal gyrus in the gamer group, both at T1 and at T2. Furthermore, a positive increase in the rs-FC between the cerebellum, Heschl's gyrus and the middle frontal gyrus paralleled improvements of in-gaming performance. In addition, baseline rs-FC of left supramarginal gyrus, left middle frontal gyrus and right cerebellum were associated with individual changes in videogame performance. Finally, enhancement of perceptual and attentional measures was observed at both T1 and T2, which correlated with a pattern of rs-FC changes in bilateral occipito-temporal regions belonging to the visual and attention fMRInetworks. The present findings increase knowledge on functional connectivity changes induced by action videogames, pointing to a greater and long-lasting synchronization between brain regions associated with spatial orientation, visual discrimination and motor learning even after a relatively short multi-day gaming exposure.

Hippocampal Functional Connectivity Mediates the Impact of Acceptance on Posttraumatic Stress Symptom Severity.

Investigation in posttraumatic stress disorder (PTSD) shows a negative association between patients’ degrees of acceptance (the willingness to face unwanted private experiences while pursuing one’s values and goals) and those of clinical symptom severity, suggesting that experiential acceptance is a protective factor of symptoms or an early indicator of resilience after trauma. However, neural mechanisms involved in the relationship between these two variables have yet to be elucidated. Thus, we here investigate whether there are neural mechanisms mediating such relationship using whole-brain voxel-level mediation analysis with seed-based resting-state functional connectivity (RSFC) maps generated by hippocampal subregion seeds in accident survivors (n = 33). We found that the correlation between patients’ acceptance and symptom severity was mediated by the RSFC strength between left hippocampal body and left lateral occipital cortex adjacent to superior parietal cortex, the areas related to flashbacks. Our result provides novel evidence that hippocampal RSFC mediates the effect of experiential acceptance on posttraumatic stress symptom severity. If further refined and validated, the finding may aid to the identification of biomarkers to intervention and prevention programs for patients with PTSD.

Altered structural and functional connectivity in CSF1R-related leukoencephalopathy.

CSF1R-related leukoencephalopathy is a rare white-matter encephalopathy characterized by motor and neuropsychiatric symptoms due to colony-stimulating factor 1 receptor (CSF1R) gene mutation. Few studies have investigated the intrinsic brain alternations of patients with CSF1R-related leukoencephalopathy. We aim to evaluate the structural and functional changes in those patients. Seven patients with CSF1R-related leukoencephalopathy and 15 age-matched healthy controls (HCs) underwent multimodal magnetic resonance imaging (MRI), including high-resolution T1-weighted imaging, T2-weighted fluid attenuated inversion recovery imaging, diffusion-weighted imaging, diffusion kurtosis imaging (DKI) and resting-state functional MRI. First, to detect structural alterations, the gray matter volumes were compared using voxel-based morphometry analyses. Second, DKI parametric maps were used to evaluate the white matter (WM) connectivity changes. Finally, we constructed a seed-based resting-state functional connectivity matrix based on 90 regions of interest and examined the functional network changes of CSF1R-related leukoencephalopathy. Unlike the HCs, patients with CSF1R-related leukoencephalopathy predominantly had morphological atrophy in the bilateral thalamus and left hippocampus. In addition, the abnormal diffusivity was mainly distributed in the splenium of the corpus callosum, periventricular regions, centrum semiovale, subcortical U-fibers and midline cortex structures. Moreover, the patients had significantly reduced functional connectivity between the bilateral caudate nucleus and their contralateral hippocampus. Therefore, in addition to hyperintensity on the T2-weighted images, CSF1R-related leukoencephalopathy also showed abnormal structural and functional alterations, including subcortical atrophy and reduced functional connectivity, as well as altered diffuse parameters in the WM and subcortical regions. These findings expand our understanding of the potential pathophysiologic mechanism behind this hereditary disease.

Cerebellar transcranial alternating current stimulation in the gamma range applied during the acquisition of a novel motor skill

The development of novel strategies to augment motor training success is of great interest for healthy persons and neurological patients. A promising approach is the combination of training with transcranial electric stimulation. However, limited reproducibility and varying effect sizes make further protocol optimization necessary. We tested the effects of a novel cerebellar transcranial alternating current stimulation protocol (tACS) on motor skill learning. Furthermore, we studied underlying mechanisms by means of transcranial magnetic stimulation and analysis of fMRI-based resting-state connectivity. N = 15 young, healthy participants were recruited. 50 Hz tACS was applied to the left cerebellum in a double-blind, sham-controlled, cross-over design concurrently to the acquisition of a novel motor skill. Potential underlying mechanisms were assessed by studying short intracortical inhibition at rest (SICIrest) and in the premovement phase (SICImove), intracortical facilitation at rest (ICFrest), and seed-based resting-state fMRI-based functional connectivity (FC) in a hypothesis-driven motor learning network. Active stimulation did not enhance skill acquisition or retention. Minor effects on striato-parietal FC were present. Linear mixed effects modelling identified SICImove modulation and baseline task performance as the most influential determining factors for predicting training success. Accounting for the identified factors may allow to stratify participants for future training-based interventions.

Altered intrinsic connectivity distribution in internet gaming disorder and its associations with psychotherapy treatment outcomes.

Alterations in brain connectivity have been implicated in internet gaming disorder (IGD). However, little is known about alterations in whole-brain connectivity and their associations with long-term treatment outcomes. Here, we used a relatively new analytic approach, intrinsic connectivity distribution (ICD) analysis, to examine brain connectivity in 74 IGD participants and 41 matched healthy controls (HCs) and conducted post hoc seed-based resting-state functional connectivity (rsFC) analyses based on the ICD findings. We also examined how these findings related to outcomes involving a craving behavioral intervention (CBI) for IGD. IGD participants showed less whole-brain connectivity in the left angular gyrus and ventromedial prefrontal cortex (vmPFC) compared with HC participants. Seed-based rsFC analyses revealed that the left angular gyrus in the IGD group showed less connectivity with areas involved in the default-mode network and greater connectivity with areas in the salience and executive control networks. CBI was associated with improved connectivity within regions in the default-mode network and regions across the default-mode and salience networks. ICD-identified connectivity differences in the left angular gyrus and vmPFC were related to changes in craving and severity of addiction 6 months after the intervention. The findings suggest that IGD is associated with alterations in brain connectivity that may be sensitive to interventions. Thus, the findings have implications for understanding mechanisms underlying CBI effects and for further treatment development.

Enhanced cerebro-cerebellar functional connectivity reverses cognitive impairment following electroconvulsive therapy in major depressive disorder.

Electroconvulsive therapy (ECT), a rapidly acting and effective treatment for major depressive disorder (MDD), is frequently accompanied by cognitive impairment. Recent studies have documented that ECT reorganizes dysregulated inter/intra- connected cerebral networks, including the affective network, the cognitive control network(CCN) and default mode network (DMN).Moreover, cerebellum is thought to play an important role in emotion regulation and cognitive processing. However, little is known about the relationship between cerebro-cerebellar connectivity alterations following ECT and antidepressant effects or cognitive impairment. We performed seed-based resting-state functional connectivity (RSFC) analyses in 28 MDD patients receiving ECT and 20 healthy controls to identify cerebro-cerebellar connectivity differences related to MDD and changes induced by ECT. Six seed regions (three per hemisphere) in the cerebrum were selected for RSFC, corresponding to the affective network, CCN and DMN, to establish cerebro-cerebellar functional connectivity with cerebellum. MDD patients showed increased RSFC between left sgACC and left cerebellar lobule VI after ECT. Ggranger causality analyses (GCA) identified the causal interaction is from left cerebellar lobule VI to left sgACC. Furthermore, increased effective connectivity from left cerebellar lobule VI to left sgACC exhibited positively correlated with the change in verbal fluency test (VFT) score following ECT (r = 0.433, p = 0.039). Our findings indicate that the enhanced cerebro-cerebellar functional connectivity from left lobule VI to left sgACC may ameliorate cognitive impairment induced by ECT. This study identifies a potential neural pathway for mitigation of cognitive impairment following ECT.

Clinical predictivity of thalamic sub-regional connectivity in clinically isolated syndrome: a 7-year study.

Here, we explored trajectories of sub-regional thalamic resting state (RS) functional connectivity (FC) modifications occurring in clinically isolated syndrome (CIS) patients early after their first clinical episode, and assessed their relationship with disability over 7 years. RS fMRI and clinical data were prospectively acquired from 59 CIS patients and 13 healthy controls (HC) over 2 years. A clinical re-assessment was performed in 53 (89%) patients after 7 years. Using a structural connectivity-based atlas, five thalamic sub-regions (frontal, motor, postcentral, occipital, and temporal) were used for seed-based RS FC. Thalamic RS FC abnormalities and their longitudinal changes were correlated with disability. Thirty-nine (66.1%) patients suffered a second clinical relapse, but the median EDSS remained stable over time. At baseline, CIS patients vs HC showed reduced RS FC (p < 0.001, uncorrected) with: (1) frontal cortices, for the whole thalamus, occipital, postcentral, and temporal thalamic sub-regions, (2) occipital cortices, for the occipital thalamic sub-region. In CIS, the longitudinal analysis revealed at year 2 vs baseline: (1) no significant whole-thalamic RS FC changes; (2) reduction of motor, postcentral, and temporal sub-regional RS FC with occipital cortices (p < 0.05, corrected); (3) an increase (p < 0.001, uncorrected) of postcentral and occipital sub-regional thalamic RS FC with frontal cortices, left putamen, and ipsi- and contralateral thalamus, this latter correlating with less severe clinical disability at year 7. Thalamo-cortical disconnections were present in CIS mainly in thalamic sub-regions closer to the third ventricle early after the demyelinating event, evolved in the subsequent 2 years, and were associated with long-term clinical disability.

Large-scale network dysfunction in the acute state compared to the remitted state of bipolar disorder: A meta-analysis of resting-state functional connectivity.

BackgroundBipolar disorder (BD) is a mental disorder characterized by mood fluctuations between an acute episodic state of either mania or depression and a clinically remitted state. Dysfunction of large-scale intrinsic brain networks has been demonstrated in this disorder, but it remains unknown whether those network alterations are related to different states.MethodsIn the present study, we performed a meta-analysis of whole-brain seed-based resting-state functional connectivity (rsFC) studies in BD patients to compare the intrinsic function of brain networks between episodic and remitted states. Thirty-nine seed-based voxel-wise rsFC datasets from thirty publications (1047 BD patients vs 1081 controls) were included in the meta-analysis. Seeds were categorized into networks by their locations within a priori functional networks. Seed-based d mapping analysis of between-state effects identified brain systems in which different states were associated with increased connectivity or decreased connectivity within and between each seed network.FindingsWe found that BD patients presented decreased connectivity within the affective network (AN) in acute episodes but not in the remitted state of the illness. Similar decreased connectivity within the default-mode network (DMN) was also found in the acute state, but it was replaced by increased connectivity in the remitted state. In addition, different patterns of between-network dysconnectivity were observed between the acute and remitted states.InterpretationThis study is the first to identify different patterns of intrinsic function in large-scale brain networks between the acute and remitted states of BD through meta-analysis. The findings suggest that a shift in network function between the acute and remitted states may be related to distinct emotional and cognitive dysfunctions in BD, which may have important implications for identifying clinically relevant biomarkers to guide alternative treatment strategies for BD patients during active episodes or remission.FundingThis study was supported by grants from the National Natural Science Foundation of China (81171488, 81671669 and 81820108018) and by a Sichuan Provincial Youth Grant (2017JQ0001).

Distinct neural networks associated with obsession and delusion: a connectome-wide association study.

Obsession and delusion are theoretically distinct from each other in terms of reality testing. Despite such phenomenological distinction, no extant studies have examined the identification of common and distinct neural correlates of obsession and delusion by employing biologically grounded methods. Here, we investigated dimensional effects of obsession and delusion spanning across the traditional diagnostic boundaries reflected upon the resting-state functional connectivity (RSFC) using connectome-wide association studies (CWAS). Our study sample comprised of 96 patients with obsessive-compulsive disorder, 75 patients with schizophrenia, and 65 healthy controls. A connectome-wide analysis was conducted to examine the relationship between obsession and delusion severity and RFSC using multivariate distance-based matrix regression. Obsession was associated with the supplementary motor area, precentral gyrus, and superior parietal lobule, while delusion was associated with the precuneus. Follow-up seed-based RSFC and modularity analyses revealed that obsession was related to aberrant inter-network connectivity strength. Additional inter-network analyses demonstrated the association between obsession severity and inter-network connectivity between the frontoparietal control network and the dorsal attention network. Our CWAS study based on the Research Domain Criteria (RDoC) provides novel evidence for the circuit-level functional dysconnectivity associated with obsession and delusion severity across diagnostic boundaries. Further refinement and accumulation of biomarkers from studies embedded within the RDoC framework would provide useful information in treating individuals who have some obsession or delusion symptoms but cannot be identified by the category of clinical symptoms alone.

Alterations of grey matter volumes and network-level functions in patients with stable chronic obstructive pulmonary disease

ObjectiveThe purpose of this study was to investigate structural and functional alterations of the brain in the patients with stable chronic obstructive pulmonary disorder (COPD) and further investigate how these alterations correlated to parameters of pulmonary function test, cognitive function and disease duration in patients with COPD. MethodForty-five patients with stable COPD and forty age- and gender-matched healthy controls were enrolled into this study. Both resting-state fMRI and structural MRI were acquired for each participant. Voxel-based morphology was utilized to analyze alterations of the grey matter volume (GMV), and the seed-based resting-state functional connectivity (FC) was used to evaluate the network-level functional alterations. ResultsCompared to healthy controls, patients with stable COPD showed decreased GMV in the left supramarginal gyrus/precentral gyrus (SMG/PreCG), bilateral posterior midcingulate cortex (pMCC), right middle occipital gyrus (MOG) and right SMG. Furthermore, COPD patients mainly showed decreased FC within the visual network, frontoparietal network and other brain regions. Subsequent correlational analyses revealed that the decreased FC within visual network, frontoparietal network were positively correlated with the Montreal Cognitive Assessment score, language-domain score, attention-domain score and disease duration in patients with COPD. ConclusionOur findings provided evidence that COPD patients showed decreased GMV and regional and network-level functional alterations within the visual network, frontoparietal network and other networks. We speculated that atrophic GMV and FC of visual network and frontoparietal network are involved in the neural mechanism of mild cognitive impairment in stable COPD patients.

Dorsal striatal functional connectivity changes in Internet gaming disorder: A longitudinal magnetic resonance imaging study.

Internet gaming disorder (IGD) is a behavioral addiction involving excessive online game use despite negative psychosocial consequences. Unrestricted online gaming may lead to changes in striatal activity and the relationship between the striatum and other cortical regions. This study investigated structural and functional abnormalities involving the striatum through longitudinal follow-up magnetic resonance imaging (MRI) assessments. Eighteen young males with IGD (mean age: 23.8 ± 2.0 years) and 18 controls (mean age: 23.9 ± 2.7 years) were evaluated. Subjects were reassessed ≥1 year after the first visit (mean follow-up duration: 22.8 ± 6.7 months), using voxel-based morphometry and seed-based resting-state functional connectivity (FC) analyses in seed regions of the dorsal and ventral striatum. Subjects with IGD had smaller gray matter volume (GMV) in the anterior/middle cingulate cortex compared with controls during initial and follow-up assessments. They exhibited decreased FC between the left dorsal putamen and left medial prefrontal cortex (mPFC) compared with controls. They exhibited increased FC strength between the right dorsal putamen and right middle occipital gyrus (MOG) during follow-up. Subjects with IGD showed a significant correlation between changes in the dorsal putamen-MOG FC and gaming time per day. Young males with IGD showed an altered FC pattern in the dorsal striatum during follow-up. FC of the dorsal striatum in IGD increased in the mPFC and decreased in the MOG. These findings showed that IGD was accompanied by weakening of prefrontal control and strengthening of the sensorimotor network, suggesting that uncontrolled gaming may be related with functional neural changes in the dorsal striatum.

Altered functional connectivity of the nucleus accumbens subdivisions in amphetamine-type stimulant abusers: a resting-state fMRI study

BackgroundThe growing abuse of amphetamine-type stimulants leads to new challenges to human health. A possible addiction mechanism has been proposed by altered functional architecture of the nucleus accumbens (NAc) during resting state. NAc contains different subdivisions and they may play different roles in addiction. The aim of the present study was to examine whether there are common or distinct patterns of functional connectivity of the NAc subdivisions in amphetamine-type stimulant abusers (ATSAs).MethodsThe present study recruited 17 male ATSAs and 22 healthy male controls. All the subjects underwent resting-state functional magnetic resonance imaging (fMRI) with their eyes closed. The NAc was divided into core-like and shell-like subdivisions. We used seed-based resting-state functional connectivity (RSFC) analyses to identify differences in brain functional architecture between ATSAs and healthy controls (HCs).ResultsATSAs had lower positive RSFCs with all of the NAc subdivisions over the left orbital part of superior frontal gyrus and higher positive RSFCs with the NAc subdivisions over the left opercular part of inferior frontal gyrus than HCs, which indicates common abnormalities across the NAc subdivisions in ATSAs. In addition, the RSFCs between the NAc subdivisions and the left orbital part of superior frontal gyrus were negatively correlated with the addiction severity in ATSAs.ConclusionThese results provide evidence that there are common RSFC patterns of the NAc subdivisions in ATSAs. The abnormality indicated by disrupted functional connectivity between the NAc subdivisions and prefrontal cortex suggests abnormal interaction between the rewarding process and cognitive control in ATSAs. Our results shed insight on the neurobiological mechanisms of ATSA and suggest potential novel therapeutic targets for treatment and intervention of ATSAs.

S.13.04 Interplay between inflammation and neuroplasticity in promoting antidepressant treatment

Alcohol consumption during adolescence might impede normal brain development, while more excessive drinking during this period poses a risk for developing alcohol use disorder. Here it was tested whether nucleus accumbens (NAcc) resting-state functional connectivity could be associated with lifetime drinking behavior in young adults, and whether it could predict their alcohol consumption during a one-year follow-up period. The current investigation was part of the bicentric Learning and Alcohol Dependence (LeAD) population-based prospective cohort study. One hundred and eighty-four 18-year-old male social drinking volunteers without a lifetime diagnosis of psychotic, bipolar, or alcohol use disorder were recruited from the general population. Seed-based resting-state functional connectivity was calculated for the bilateral NAcc in each participant. Across the group, the association between NAcc functional connectivity and lifetime alcohol consumption was assessed (p < .05, whole-brain FWE-corrected). Individual connectivity values were then extracted from regions that demonstrated a significant association to predict drinking behavior during a one-year follow-up period (n = 143), correcting for lifetime alcohol consumption. Weaker connectivity between the left NAcc and bilateral dorsolateral prefrontal cortex, inferior frontal gyrus, left caudate nucleus, left putamen, and left insula was associated with greater lifetime alcohol consumption, as well as with greater alcohol consumption during the one-year follow-up period. Our findings underscore the relevance of fronto-striatal connectivity to the field of alcohol research. Impaired prefrontal cognitive control might mediate excessive drinking behavior and may prove a promising biomarker for risk of future alcohol (ab)use.

Nucleus accumbens connectivity at rest is associated with alcohol consumption in young male adults

Alcohol consumption during adolescence might impede normal brain development, while more excessive drinking during this period poses a risk for developing alcohol use disorder. Here it was tested whether nucleus accumbens (NAcc) resting-state functional connectivity could be associated with lifetime drinking behavior in young adults, and whether it could predict their alcohol consumption during a one-year follow-up period. The current investigation was part of the bicentric Learning and Alcohol Dependence (LeAD) population-based prospective cohort study. One hundred and eighty-four 18-year-old male social drinking volunteers without a lifetime diagnosis of psychotic, bipolar, or alcohol use disorder were recruited from the general population. Seed-based resting-state functional connectivity was calculated for the bilateral NAcc in each participant. Across the group, the association between NAcc functional connectivity and lifetime alcohol consumption was assessed (p < .05, whole-brain FWE-corrected). Individual connectivity values were then extracted from regions that demonstrated a significant association to predict drinking behavior during a one-year follow-up period (n = 143), correcting for lifetime alcohol consumption. Weaker connectivity between the left NAcc and bilateral dorsolateral prefrontal cortex, inferior frontal gyrus, left caudate nucleus, left putamen, and left insula was associated with greater lifetime alcohol consumption, as well as with greater alcohol consumption during the one-year follow-up period. Our findings underscore the relevance of fronto-striatal connectivity to the field of alcohol research. Impaired prefrontal cognitive control might mediate excessive drinking behavior and may prove a promising biomarker for risk of future alcohol (ab)use.

MODELLING POLYGENIC AND ENVIRONMENTAL PREDICTORS: A SYSTEMATIC APPROACH TO GENE-ENVIRONMENT INTERACTIONS ACROSS COMPLEX TRAITS

Alcohol consumption during adolescence might impede normal brain development, while more excessive drinking during this period poses a risk for developing alcohol use disorder. Here it was tested whether nucleus accumbens (NAcc) resting-state functional connectivity could be associated with lifetime drinking behavior in young adults, and whether it could predict their alcohol consumption during a one-year follow-up period. The current investigation was part of the bicentric Learning and Alcohol Dependence (LeAD) population-based prospective cohort study. One hundred and eighty-four 18-year-old male social drinking volunteers without a lifetime diagnosis of psychotic, bipolar, or alcohol use disorder were recruited from the general population. Seed-based resting-state functional connectivity was calculated for the bilateral NAcc in each participant. Across the group, the association between NAcc functional connectivity and lifetime alcohol consumption was assessed (p < .05, whole-brain FWE-corrected). Individual connectivity values were then extracted from regions that demonstrated a significant association to predict drinking behavior during a one-year follow-up period (n = 143), correcting for lifetime alcohol consumption. Weaker connectivity between the left NAcc and bilateral dorsolateral prefrontal cortex, inferior frontal gyrus, left caudate nucleus, left putamen, and left insula was associated with greater lifetime alcohol consumption, as well as with greater alcohol consumption during the one-year follow-up period. Our findings underscore the relevance of fronto-striatal connectivity to the field of alcohol research. Impaired prefrontal cognitive control might mediate excessive drinking behavior and may prove a promising biomarker for risk of future alcohol (ab)use.

Structural and Functional Connectivity of the Anterior Cingulate Cortex in Patients With Borderline Personality Disorder.

BackgroundEmerging evidences supported the hypothesis that emotional dysregulation results from aberrant connectivity within the fronto-limbic neural networks in patients with borderline personality disorder (BPD). Considering its important role in emotional regulation, the anterior cingulate cortex (ACC) has not yet been fully explored in BPD patients. Therefore, using the seed-based resting state functional connectivity (rsFC) and probabilistic fiber tracking, we aimed to explore the alterations of functional and structural connectivity (SC) of the ACC in patients with BPD.MethodsA cohort of 50 unmedicated, young BPD patients and 54 sex-, age-, and education-matched healthy controls (HCs) completed psychological tests and underwent rs-fMRI and diffuse tensor imaging (DTI) scanning. Rs-FC analysis and probabilistic fiber tracking were used to plot SC and FC of the ACC.ResultsWith the left ACC selected as a seed, BPD patients exhibited increased rsFC and abnormal SC with the right middle frontal gyrus (MFG), and decreased rsFC with the left middle temporal gyrus (MTG), compared with HCs. Additionally, negative cognitive emotion regulation and depressive symptoms both correlated negatively with the rsFC of the left ACC in BPD patients.ConclusionAbnormal SC and FC of the ACC underlie the deficient emotional regulation circuitry in BPD patients. Such alterations may be important biomarkers of BPD and thus could point to potential BPD treatment targets.

PTSD and its dissociative subtype through the lens of the insula: Anterior and posterior insula resting-state functional connectivity and its predictive validity using machine learning.

Individuals with post-traumatic stress disorder (PTSD) typically experience states of reliving and hypervigilance; however, the dissociative subtype of PTSD (PTSD+DS) presents with additional symptoms of depersonalization and derealization. Although the insula is critical to emotion processing, its association with these contrasting symptom profiles is yet to be fully delineated. Accordingly, we investigated insula subregion resting-state functional connectivity patterns among individuals with PTSD, PTSD+DS, and healthy controls. Using SPM12 and PRONTO software, we implemented a seed-based resting-state functional connectivity approach, along with multiclass Gaussian process classification machine learning, respectively, in order to evaluate unique patterns and the predictive validity of insula subregion connectivity among individuals with PTSD (n=84), PTSD+DS (n=49), and age-matched healthy controls (n=51). Ascompared to PTSD and PTSD+DS, healthy controls showed increased right anterior and posterior insula connectivity with frontal lobe structures. By contrast, PTSD showed increased bilateral posterior insula connectivity with subcortical structures, including the periaqueductal gray. Strikingly, ascompared to PTSD and controls, PTSD+DS showed increased bilateral anterior and posterior insula connectivity with posterior cortices, including the left lingual gyrus and the left precuneus. Moreover, machine learning analyses were able to classify PTSD, PTSD+DS, and controls using insula subregion connectivity patterns with 80.4% balanced accuracy (p < .01). These findings suggest a neurobiological distinction between PTSD and its dissociative subtype with regard to insula subregion functional connectivity patterns. Furthermore, machine learning algorithms were able to utilize insula resting-state connectivity patterns to discriminate between participant groups with high predictive accuracy.

Frontostriatal Resting State Functional Connectivity in Resilient and Non-Resilient Adolescents with a Family History of Alcohol Use Disorder.

Objectives: Youth with parental substance use disorder (family-history positive [FH+]) are at an elevated risk for substance use problems, but not all FH+ youth experience this outcome. Frontostriatal brain networks involved in inhibitory control and reward responsivity underlie risk-taking behaviors, but the role of these networks in substance use heterogeneity among FH+ youth has not been examined. The present study examined resting state functional connectivity (RSFC) in frontostriatal networks in FH+ youth with and without risky substance use. Methods: Participants were 36 FH+ adolescents (mean age 14.96 years at the scan date; 36% female) from a longitudinal, community-based functional magnetic resonance imaging study enriched for parental alcohol use disorder. Groups were based on the absence (resilient) or presence (high-risk) of at least one occasion of any substance use by age 14 and also use of at least two different types of substances by the most recent substance use assessment (mean age 16.89 years). Bilateral masks of the dorsolateral prefrontal cortex (DLPFC) and the nucleus accumbens were used for seed-based RSFC due to the importance of these regions in executive control and salience networks, respectively. Results: Compared with FH+/high-risk youth, FH+/resilient youth displayed greater connectivity between the left DLPFC seed and the left posterior cingulate cortex. No other brain regions showed significantly different RSFC between resilient and high-risk groups. Conclusion: FH+/resilient youth showed stronger synchrony between brain regions associated with cognitive control, particularly those associated with flexible adaptation of thoughts and behaviors. Although preliminary, the results of this study set the stage for a continued focus on risk-group heterogeneity to better identify neural markers of resilience against substance use problems in vulnerable populations.

In Trauma-Exposed Individuals, Self-reported Hyperarousal and Sleep Architecture Predict Resting-State Functional Connectivity in Frontocortical and Paralimbic Regions

BackgroundSymptoms of posttraumatic stress disorder (PTSD) reflect abnormalities in large-scale brain networks. In individuals with recent trauma exposure, we examined associations of seed-based resting-state functional connectivity (rs-FC) with posttraumatic symptoms and sleep. We hypothesized that more severe PTSD symptoms and poorer sleep quality would predict 1) greater rs-FC between fear-related seeds and other fear-related regions and 2) lesser rs-FC between fear-related seeds and emotion-regulatory regions. MethodsSeventy-four participants who had experienced a DSM-5 criterion A stressor within the past 2 years and ranged from asymptomatic to fully meeting criteria for PTSD diagnosis underwent 14 days of actigraphy and sleep diaries, a night of ambulatory polysomnography, and a functional magnetic resonance imaging resting-state scan at 3T. rs-FC measures of 5 fear-related seeds and 1 emotion regulatory seed with regions of the anterior cerebrum were correlated with PTSD symptoms, objective and subjective habitual sleep quality, and sleep architecture. ResultsLonger objective habitual sleep onset latency was associated with greater connectivity between fear-related seeds and other regions of the salience network. Greater PTSD symptoms were associated with less connectivity between fear-related seeds and anterior emotion regulatory regions, whereas greater percent slow wave sleep was associated with more connectivity between these regions. However, other objective and subjective measures reflecting better habitual sleep quality were associated with less rs-FC between these regions. ConclusionsLonger sleep onset latency predicted greater rs-FC among fear-related areas. More severe PTSD symptoms predicted less rs-FC between fear and fear regulatory regions reflecting putatively reduced top-down fear regulation. Some (e.g., percent slow wave sleep), but not all sleep indices predicted greater top-down fear regulation.