Differences In rsFC Research Articles

Robustness of sex-differences in functional connectivity over time in middle-aged marmosets

Nonhuman primates (NHPs) are an essential research model for gaining a comprehensive understanding of the neural mechanisms of neurocognitive aging in our own species. In the present study, we used resting state functional connectivity (rsFC) to investigate the relationship between prefrontal cortical and striatal neural interactions, and cognitive flexibility, in unanaesthetized common marmosets (Callithrix jacchus) at two time points during late middle age (8 months apart, similar to a span of 5–6 years in humans). Based on our previous findings, we also determine the reproducibility of connectivity measures over the course of 8 months, particularly previously observed sex differences in rsFC. Male marmosets exhibited remarkably similar patterns of stronger functional connectivity relative to females and greater cognitive flexibility between the two imaging time points. Network analysis revealed that the consistent sex differences in connectivity and related cognitive associations were characterized by greater node strength and/or degree values in several prefrontal, premotor and temporal regions, as well as stronger intra PFC connectivity, in males compared to females. The current study supports the existence of robust sex differences in prefrontal and striatal resting state networks that may contribute to differences in cognitive function and offers insight on the neural systems that may be compromised in cognitive aging and age-related conditions such as mild cognitive impairment and Alzheimer’s disease.

Violence exposure, affective style, and stress-induced changes in resting state functional connectivity.

Chronic childhood stress is linked to greater susceptibility to internalizing disorders in adulthood. Specifically, chronic stress leads to changes in brain connectivity patterns, and, in turn, affects psychological functioning. Violence exposure, a chronic stressor, increases stress reactivity and disrupts emotion regulation processes. However, it is unclear to what extent violence exposure affects the neural circuitry underlying emotion regulation. Individual differences in affective style also moderate the impact of stress on psychological function and can thus alter the relationship between violence exposure and brain function. Resting-state functional connectivity (rsFC) is an index of intrinsic brain activity. Stress-induced changes in rsFC between the amygdala, hippocampus, and prefrontal cortex (PFC) are associated with emotion dysregulation and may elucidate how affective style modulates the relationship between violence exposure and brain connectivity. Therefore, the present study examined the impact of violence exposure and affective style on stress-induced changes in rsFC. Participants (n = 233) completed two 6-minute resting-state functional magnetic resonance imaging scans, one before (pre-stress) and one after (post-stress) a psychosocial stress task. The bilateral amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) were used as seed regions for rsFC analyses. Significant stress-induced changes in the prefrontal, fronto-limbic, and parieto-limbic rsFC were observed. Further, pre-stress to post-stress differences in rsFC varied with violence exposure and affective style. These findings suggest that prefrontal, fronto-limbic, and parieto-limbic connectivity is associated with the emotional response to stress and provide new insight into the neural mechanisms through which affective style moderates the impact violence exposure has on the brain.

Cannabidiol normalizes resting-state functional connectivity in treatment-resistant epilepsy

ObjectiveResting-state (rs) network dysfunction is a contributing factor to treatment resistance in epilepsy. In treatment-resistant epilepsy (TRE), pharmacological and nonpharmacological therapies have been shown to improve such dysfunction. In this study, our goal was to prospectively evaluate the effect of highly purified plant-derived cannabidiol (CBD; Epidiolex®) on rs functional magnetic resonance imaging (fMRI) functional connectivity (rs-FC). We hypothesized that CBD would change and potentially normalize the rs-FC in TRE. MethodsTwenty-two of 27 participants with TRE completed all study procedures including longitudinal pre-/on-CBD rs-fMRI (8M/14F, mean age = 36.2 ± 15.9 years, TRE duration = 18.3 ± 12.6 years); there were no differences in age (p = 0.99) or sex (p = 0.15) between groups. Assessments collected included seizure frequency (SF), Chalfont Seizure Severity Scale (CSSS), Columbia Suicide Severity Rating Scale (C-SSRS), Adverse Events Profile (AEP), and Profile of Mood States (POMS). Twenty-three healthy controls (HCs) received rs-fMRI and POMS once. ResultsParticipants with TRE showed average decrease of 71.7% in SF (p < 0.0001) and improved CSSS, AEP, and POMS confusion, depression, and fatigue subscores (all p < 0.05) on-CBD with POMS scores becoming similar to those of HCs. Paired t-tests showed significant pre-/on-CBD changes in rs-FC in cerebellum, frontal areas, temporal areas, hippocampus, and amygdala with some of them correlating with improvement in behavioral measures. Significant differences in rs-FC between pre-CBD and HCs were found in cerebellum, frontal, and occipital regions. After controlling for changes in SF with CBD, these differences were no longer present when comparing on-CBD to HCs. SignificanceThis study indicates that highly purified CBD modulates and potentially normalizes rs-FC in the epileptic brain. This effect may underlie its efficacy. This study provides Class III evidence for CBD's normalizing effect on rs-FC in TRE.

Sex Differences in Internalizing Symptoms and Amygdala Functional Connectivity in Neurotypical Youth

Amygdala resting-state functional connectivity (rsFC) is altered in adolescents with internalizing disorders, though the relationship between rsFC and subclinical symptomatology in neurotypical youth remains unclear. Here we examined whether amygdala rsFC varied across a continuum of internalizing symptoms in 110 typically-developing (TD) youths 8 to 17 years old using functional magnetic resonance imaging (fMRI). We assessed overall internalizing symptoms, as well as anxious-depressed, withdrawn-depressed, and somatic complaints. Given known sex differences in the prevalence of internalizing disorders, we compared connectivity between males and females. As compared to males, females with greater internalizing, anxious-depressed, and somatic symptoms displayed greater connectivity with the cingulate gyrus, insula, and somatosensory cortices. In contrast, males with greater anxious-depressed symptoms demonstrated weaker connectivity with the subcallosal prefrontal cortex. Sex differences in rsFC in relation to symptom severity were evident for the whole amygdala and for two of its subnuclei (centromedial and superficial amygdala). Overall, results suggest that, for females, higher internalizing symptoms are associated with greater rsFC between the amygdala and regions implicated in emotional and somatosensory processing, salience detection, and action selection. Future longitudinal investigations are needed to determine whether this hyperconnectivity may confer resilience to, or pose risk for, the development of internalizing disorders.

Beneath the surface: hyper-connectivity between caudate and salience regions in ADHD fMRI at rest.

Attention-Deficit/Hyperactivity Disorder (ADHD) comprises disturbances in attention, emotional regulation, and reward-related processes. In spite of the active efforts in researching neurofunctional correlates of these symptoms, how the activity of subcortical regions-such as basal ganglia-is related to ADHD has yet to be clarified. More specifically, how age may influence the critical changes observed in functional dynamics from childhood to adulthood remains relatively unexplored. We hence selected five core subcortical regions (amygdala, caudate, putamen, pallidum and hippocampus) as regions of interest from the previous literature, measuring their whole-brain voxel-wise rsFC in a sample of 95 ADHD and 90 neurotypical children and adolescents aged from 7 to 18. The only subcortical structure showing significant differences in rsFC was the caudate nucleus. Specifically, we measured increased rsFC with anterior cingulate and right insula, two mesolimbic regions pertaining to the Salience Network. The degree of hyper-rsFC positively correlated with ADHD symptomatology, and showed different patterns of evolution in ADHD vs neurotypical subjects. Finally, the rsFC scores allowed a fair discrimination of the ADHD group (Area Under the Curve ≥ 0.7). These findings shed further light on the fundamental role covered by subcortical structures in ADHD pathogenesis and neurodevelopment, providing new evidence to fill the gap between neurofunctional and clinical expressions of ADHD.

Correlates of Normal and Abnormal General Movements in Infancy and Long-Term Neurodevelopment of Preterm Infants: Insights from Functional Connectivity Studies at Term Equivalence.

Preterm infants born before 32 weeks gestation have increased risks for neurodevelopmental impairment at two years of age. How brain function differs between preterm infants with normal or impaired development is unknown. However, abnormal spontaneous motor behavior at 12–15 weeks post-term age is associated with neurodevelopmental impairment. We imaged brain blood oxygen level-dependent signals at term-equivalent age in 62 infants born at <32 weeks gestation and explored whether resting state functional connectivity (rsFC) differed with performances on the General Movement Assessment (GMA) at 12–15 weeks, and Bayley III scores at two years of corrected age. Infants with aberrant general movements exhibited decreased rsFC between the basal ganglia and regions in parietal and frontotemporal lobes. Infants with normal Bayley III cognitive scores exhibited increased rsFC between the basal ganglia and association cortices in parietal and occipital lobes compared with cognitively impaired children. Infants with normal motor scores exhibited increased rsFC between the basal ganglia and visual cortices, compared with children with motor impairment. Thus, the presence of abnormal general movements is associated with region-specific differences in rsFC at term. The association of abnormal long-term neurodevelopmental outcomes with decreased rsFC between basal ganglia and sub-score specific cortical regions may provide biomarkers of neurodevelopmental trajectory and outcome.

Aberrant functional connectivity of the cingulate subregions in right-sided temporal lobe epilepsy.

Patients with temporal lobe epilepsy (TLE) have been indicated to exhibit abnormal resting-state functional connectivity (rsFC) of the cingulate cortex. However, it has remained elusive whether cingulate subregions show different connectivity patterns in TLE. The present study aimed to investigate the differences in rsFC of each cingulate subregion between patients with right-sided TLE (rTLE) and healthy controls (HCs), as well as their association with executive control performance in rTLE. A total of 27 patients with rTLE and 20 age-, sex- and education-matched healthy controls were recruited and all participants underwent resting-state functional MRI and an attention network test for the assessment executive control function. In each hemisphere, the cingulate gyrus (CG) was divided into CG-1 (dorsal area 23; A23d), CG-2 (rostroventral area 24; A24rv), CG-3 (pregenual area 32; A32p), CG-4 (ventral area 23; A23v), CG-5 (caudodorsal area 24; A24cd), CG-6 (caudal area 24; A23c) and CG-7 (subgenual area 32; A32sg). Pearson's correlation analysis was performed to assess the correlation between the altered FCs of the cingulate subregions and clinical variables. In patients with rTLE, the majority of the cingulate subregions exhibited decreased rsFC; this was primarily restricted to the right CG-2, the bilateral CG-6 and the bilateral CG-7. Increased rsFC was only detected in rTLE restricted to the left CG-1. Impairments in executive control efficiency were identified in patients with rTLE in comparison with the HCs. Significant alterations in rsFC between the cingulate subregion and the brain regions were mostly decreased (and some slightly increased), suggesting that FC may potentially have a left-side advantage in patients with rTLE. FC variations of the cingulate subregions were indicated to be specific to rTLE. In addition, increased connectivity in the left CG-1 and left superior frontal gyrus were negatively correlated with executive control performance, suggesting a compensatory mechanism on executive control deficits in pathological conditions. This information on differentially altered FC patterns of the cingulate subregions may provide a deeper understanding of the complex neurological mechanisms and executive control dysfunctions underlying rTLE.

The relationship between sleep efficiency and clinical symptoms is mediated by brain function in major depressive disorder

BackgroundSleep disturbance is a common and key symptom that affects most of patients with major depressive disorder (MDD). However, neural substrates underlying sleep disturbance and their clinical relevance in depression remain unclear. MethodsNinety-six MDD patients underwent resting-state functional MRI. Fractional amplitude of low-frequency fluctuation (fALFF) and resting-state functional connectivity (rsFC) were used to measure brain function. Overnight polysomnography was performed to objectively measure sleep efficiency (SE), which was used to classify patients into normal sleep efficiency (NSE) and low sleep efficiency (LSE) groups. Between-group differences in fALFF and rsFC were examined using two-sample t-tests. Moreover, correlation and mediation analyses were conducted to test for potential associations between SE, brain functional changes, and clinical variables. ResultsLSE group showed decreased fALFF in right cuneus, thalamus, and middle temporal gyrus compared to NSE group. MDD patients with low SE also exhibited lower rsFC of right cuneus to right lateral temporal cortex, which was associated with more severe depression and anxiety symptoms. More importantly, mediation analyses revealed that the relationships between SE and severity of depression and anxiety symptoms were significantly mediated by the altered rsFC. In addition, these low SE-related brain functional alterations were not affected by antidepressant medication and were independent of structural changes. LimitationsThe lack of healthy controls because of “first-night effect”. ConclusionThese findings not only may expand existing knowledge about neuropathology of sleep disturbance in depression, but also may inform real-world clinical practice by improving depression and anxiety symptoms through sleep regulation.

Effect of single dose N-acetylcysteine administration on resting state functional connectivity in schizophrenia

RationaleThere is interest in employing N-acetylcysteine (NAC) in the treatment of schizophrenia, but investigations of the functional signatures of its pharmacological action are scarce.ObjectivesThe aim of this study was to identify the changes in resting-state functional connectivity (rs-FC) that occur following administration of a single dose of NAC in patients with schizophrenia. A secondary aim was to examine whether differences in rs-FC between conditions were mediated by glutamate metabolites in the anterior cingulate cortex (ACC).MethodsIn a double-blind, placebo-controlled crossover design, 20 patients with schizophrenia had two MRI scans administered 7 days apart, following oral administration of either 2400 mg NAC or placebo. Resting state functional fMRI (rsfMRI) assessed the effect of NAC on rs-FC within the default mode network (DMN) and the salience network (SN). Proton magnetic resonance spectroscopy was used to measure Glx/Cr (glutamate plus glutamine, in ratio to creatine) levels in the ACC during the same scanning sessions.ResultsCompared to the placebo condition, the NAC condition was associated with reduced within the DMN and SN, specifically between the medial pre-frontal cortex to mid frontal gyrus, and ACC to frontal pole (all p < 0.04). There were no significant correlations between ACC Glx/Cr and rs-FC in either condition (p > 0.6).ConclusionsThese findings provide preliminary evidence that NAC can reduce medial frontal rs-FC in schizophrenia. Future studies assessing the effects of NAC on rs-FC in early psychosis and on repeated administration in relation to efficacy would be of interest.

Functional connectivity of music-induced analgesia in fibromyalgia

Listening to self-chosen, pleasant and relaxing music reduces pain in fibromyalgia (FM), a chronic centralized pain condition. However, the neural correlates of this effect are fairly unknown. In our study, we wished to investigate the neural correlates of music-induced analgesia (MIA) in FM patients. To do this, we studied 20 FM patients and 20 matched healthy controls (HC) acquiring rs-fMRI with a 3T MRI scanner, and pain data before and after two 5-min auditory conditions: music and noise. We performed resting state functional connectivity (rs-FC) seed-based correlation analyses (SCA) using pain and analgesia-related ROIs to determine the effects before and after the music intervention in FM and HC, and its correlation with pain reports. We found significant differences in baseline rs-FC between FM and HC. Both groups showed changes in rs-FC after the music condition. FM patients reported MIA that was significantly correlated with rs-FC decrease between the angular gyrus, posterior cingulate cortex and precuneus, and rs-FC increase between amygdala and middle frontal gyrus. These areas are related to autobiographical and limbic processes, and auditory attention, suggesting MIA may arise as a consequence of top-down modulation, probably originated by distraction, relaxation, positive emotion, or a combination of these mechanisms.

A resting-state network comparison of combat-related PTSD with combat-exposed and civilian controls.

Resting-state functional connectivity (rsFC) is an emerging means of understanding the neurobiology of combat-related post-traumatic stress disorder (PTSD). However, most rsFC studies to date have limited focus to cognitively related intrinsic connectivity networks (ICNs), have not applied data-driven methodologies or have disregarded the effect of combat exposure. In this study, we predicted that group independent component analysis (GICA) would reveal group-wise differences in rsFC across 50 active duty service members with PTSD, 28 combat-exposed controls (CEC), and 25 civilian controls without trauma exposure (CC). Intranetwork connectivity differences were identified across 11 ICNs, yet combat-exposed groups were indistinguishable in PTSD vs CEC contrasts. Both PTSD and CEC demonstrated anatomically diffuse differences in the Auditory Vigilance and Sensorimotor networks compared to CC. However, intranetwork connectivity in a subset of three regions was associated with PTSD symptom severity among executive (left insula; ventral anterior cingulate) and right Fronto-Parietal (perigenual cingulate) networks. Furthermore, we found that increased temporal synchronization among visuospatial and sensorimotor networks was associated with worse avoidance symptoms in PTSD. Longitudinal neuroimaging studies in combat-exposed cohorts can further parse PTSD-related, combat stress-related or adaptive rsFC changes ensuing from combat.

Changes in Resting-State Functional Connectivity Related to Freezing of Gait in Parkinson's Disease

Freezing of gait (FOG) is a common motor symptom in Parkinson's disease (PD) thought to arise from the dysfunctional cortico-basal ganglia-thalamic circuity. The purpose of this study was to assess the changes in brain resting-state functional connectivity (rs-FC) of subcortical structures comprising the cortico-basal ganglia-thalamic circuity in individuals with PD with and without FOG. Resting-state functional magnetic resonance imaging was acquired in 27 individuals with idiopathic PD (14 with FOG and 13 without FOG). A seed-to-voxel analysis was performed with the seeds in the bilateral basal ganglia nuclei, thalamus, and pedunculopontine nucleus. Between-group differences in rs-FC revealed that the bilateral thalamus and globus pallidus external were significantly more connected with visual areas in PD with FOG compared to PD without FOG. In addition, PD with FOG had increased connectivity between the left putamen and retrosplenial cortex as well as with the cerebellum. Our findings suggest an increased connectivity at rest of subcortical and cortical regions involved in sensory and visuospatial processing that may be compensating for sensorimotor deficits in FOG. This increased connectivity may contribute to the hypothesized overload in the cortico-basal ganglia-thalamic circuity processing capacity, which may ultimately result in FOG occurrence.

Functional network connectivity impairments and core cognitive deficits in schizophrenia.

Cognitive deficits contribute to functional disability in patients with schizophrenia and may be related to altered functional networks that serve cognition. We evaluated the integrity of major functional networks and assessed their role in supporting two cognitive functions affected in schizophrenia: processing speed (PS) and working memory (WM). Resting-state functional magnetic resonance imaging (rsfMRI) data, N = 261 patients and 327 controls, were aggregated from three independent cohorts and evaluated using Enhancing NeuroImaging Genetics through Meta Analysis rsfMRI analysis pipeline. Meta- and mega-analyses were used to evaluate patient-control differences in functional connectivity (FC) measures. Canonical correlation analysis was used to study the association between cognitive deficits and FC measures. Patients showed consistent patterns of cognitive and resting-state FC (rsFC) deficits across three cohorts. Patient-control differences in rsFC calculated using seed-based and dual-regression approaches were consistent (Cohen's d: 0.31 ± 0.09 and 0.29 ± 0.08, p < 10-4 ). RsFC measures explained 12-17% of the individual variations in PS and WM in the full sample and in patients and controls separately, with the strongest correlations found in salience, auditory, somatosensory, and default-mode networks. The pattern of association between rsFC (within-network) and PS (r = .45, p = .07) and WM (r = .36, p = .16), and rsFC (between-network) and PS (r = .52, p = 8.4 × 10-3 ) and WM (r = .47, p = .02), derived from multiple networks was related to effect size of patient-control differences in the functional networks. No association was detected between rsFC and current medication dose or psychosis ratings. Patients demonstrated significant reduction in several FC networks that may partially underlie some of the core neurocognitive deficits in schizophrenia. The strength of connectivity-cognition relationships in different networks was strongly associated with network's vulnerability to schizophrenia.

Abnormal resting-state functional connectivity of amygdala subregions in patients with obstructive sleep apnea.

Background: The amygdala is one of the core areas of the emotional circuits. Previous neuroimaging studies have revealed that patients with obstructive sleep apnea (OSA) have aberrant structure and function in several brain areas (including the amygdala). However, the resting-state functional connectivity (rs-FC) of amgydala subregions remains uncertain.Objective: To determine whether aberrant rs-FC exists between the amygdala subregions and other brain areas and whether such abnormalities are related to emotional disorders and cognitive impairment in OSA.Methods: The resting-state functional magnetic resonance imaging (rs-fMRI) data of 40 male severe OSA patients and 40 matched healthy controls (HCs) were collected. The rs-FC between the amygdala subregions and other brain areas was compared between the two groups. The correlations between aberrant rs-FC and clinical variables and neuropsychological assessments were evaluated.Results: Compared with the HCs, the OSA patients showed significantly increased rs-FC between the left dorsal amygdala (DA) and the anterior lobe of the cerebellum, among the left ventrolateral amygdala (VA), the left inferior frontal gyrus (IFG) and the left superior temporal gyrus (STG), and between the right VA and the left IFG. However, significantly decreased rs-FC was observed between the right DA and the right prefrontal cortex (PFC) in OSA patients. No regional differences in rs-FC were found between the OSA patients and HCs in the bilateral medial amygdala (MA).Conclusion: In this study, male severe OSA patients showed complex rs-FC patterns in the amygdala subregions, which may be the result of OSA-related selective damage to the amygdala, and abnormal rs-FC between the amygdala subregions and brain regions associated with emotional, cognitive and executive functions may partly explain the affective deficits and cognitive impairment observed in male severe OSA patients.

Electrophysiological correlates of cognitive symptoms in multiple sclerosis through neuromagnetic resting-state functional connectivity

Electrophysiological correlates of cognitive symptoms in multiple sclerosis through neuromagnetic resting-state functional connectivity

Intrinsic functional connectivity correlates of person-level risk for bipolar disorder in offspring of affected parents.

Offspring of parents with bipolar disorder (OBP) are at increased risk to develop bipolar disorder (BD). Alterations in resting-state functional connectivity (rsFC) have been identified in OBP; however, replication has been limited and correlation with person-level risk is unknown. A recent study found reduced rsFC between left inferior frontal gyrus (IFG) and clusters in the left insula (LINS), lentiform nucleus (LENT), and midcingulate cortex (MCING) in OBP (Roberts et al. 2017); here, we aim to extend these findings to at-risk youth. We scanned a subset of the Pittsburgh Bipolar Offspring Study, a longitudinal study of OBP and community controls. Twenty-four OBP, 20 offspring of control parents with non-bipolar psychopathology (OCP), and 27 healthy controls (HC) had acceptable rsFC data. After preprocessing steps, we assessed group differences in seed-based rsFC between the IFG and target clusters (LINS, LENT, MCING) using multivariate regression. Next, we tested whether rsFC correlated with person-level risk score and with other dimensional measures. We did not find group differences in rsFC between IFG and target regions. Within OBP, risk score negatively correlated with IFG-LINS rsFC (p = 0.002). Across groups, mood lability correlated negatively with rsFC between IFG and target regions (p = 0.0002), due to negative correlation with IFG-LINS (p = 0.0003) and IFG-MCING (p = 0.001) rsFC. While group-level differences were not replicated, IFG-LINS rsFC was negatively correlated with a person-level risk score in OBP and with mood lability (a predictor of BD) across the sample. Thus, IFG-LINS rsFC might constitute a risk marker, within OBP, for the development of BD.

Regional Prefrontal Resting-State Functional Connectivity in Posttraumatic Stress Disorder

BackgroundPrefrontal subregions, including the ventromedial prefrontal cortex (PFC), dorsomedial PFC, and dorsolateral PFC (DLPFC), are differentially implicated in the pathophysiology of posttraumatic stress disorder (PTSD), though few existing studies have examined subregional differences in resting-state functional connectivity (rsFC). We hypothesized that PTSD would involve weaker positive rsFC between ventromedial PFC, dorsomedial PFC, and other default mode network regions and increased negative rsFC between DLPFC and posterior default mode network regions. Additionally, we hypothesized that prefrontal regions exhibiting group differences in rsFC would be characterized by alterations in cortical thickness. MethodsParticipants included 36 healthy control subjects, 30 trauma-exposed control subjects, and 21 individuals with current DSM-IV PTSD resulting from community-acquired trauma. Participants completed the Clinician Administered PTSD Scale, questionnaires (Childhood Trauma Questionnaire, Adverse Childhood Events, Life Events Checklist, Beck Depression Inventory), structural neuroimaging, and resting-state functional magnetic resonance imaging. rsFC of DLPFC, ventromedial PFC, and dorsomedial PFC seeds was evaluated in SPM12 and CONN. Cortical thickness for regions with significant rsFC findings was assessed using FreeSurfer. ResultsRelative to both healthy control and trauma-exposed control subjects, individuals with PTSD showed increased negative rsFC between the DLPFC and a region of precuneus. This finding was associated with increased overall symptom severity but not with trauma load or childhood trauma exposure. Greater negative DLPFC-precuneus connectivity was associated with greater bilateral precuneus thickness. ConclusionsGiven participation of precuneus subregions in the central executive network, increased anticorrelation between right DLPFC and precuneus in this sample may reflect increased opposition between anterior and posterior central executive network hubs in PTSD.

Exploring Age-Related Changes in Resting State Functional Connectivity of the Amygdala: From Young to Middle Adulthood.

Functional connectivities of the amygdala support emotional and cognitive processing. Life-span development of resting-state functional connectivities (rsFC) of the amygdala may underlie age-related differences in emotion regulatory mechanisms. To date, age-related changes in amygdala rsFC have been reported through adolescence but not as thoroughly for adulthood. This study investigated age-related differences in amygdala rsFC in 132 young and middle-aged adults (19–55 years). Data processing followed published routines. Overall, amygdala showed positive rsFC with the temporal, sensorimotor and ventromedial prefrontal cortex (vmPFC), insula and lentiform nucleus, and negative rsFC with visual, frontoparietal, and posterior cingulate cortex and caudate head. Amygdala rsFC with the cerebellum was positively correlated with age, and rsFCs with the dorsal medial prefrontal cortex (dmPFC) and somatomotor cortex were negatively correlated with age, at voxel p < 0.001 in combination with cluster p < 0.05 FWE. These age-dependent changes in connectivity appeared to manifest to a greater extent in men than in women, although the sex difference was only evident for the cerebellum in a slope test of age regressions (p = 0.0053). Previous studies showed amygdala interaction with the anterior cingulate cortex (ACC) and vmPFC during emotion regulation. In region of interest analysis, amygdala rsFC with the ACC and vmPFC did not show age-related changes. These findings suggest that intrinsic connectivity of the amygdala evolved from young to middle adulthood in selective brain regions, and may inform future studies of age-related emotion regulation and maladaptive development of the amygdala circuits as an etiological marker of emotional disorders.

Ventral striatal dysfunction in cocaine dependence \u2013 difference mapping for subregional resting state functional connectivity

Research of dopaminergic deficits has focused on the ventral striatum (VS) with many studies elucidating altered resting state functional connectivity (rsFC) in individuals with cocaine dependence (CD). The VS comprises functional subregions and delineation of subregional changes in rsFC requires careful consideration of the differences between addicted and healthy populations. In the current study, we parcellated the VS using whole-brain rsFC differences between CD and non-drug-using controls (HC). Voxels with similar rsFC changes formed functional clusters. The results showed that the VS was divided into 3 subclusters, in the area of the dorsal-anterior VS (daVS), dorsal posterior VS (dpVS), and ventral VS (vVS), each in association with different patterns of rsFC. The three subregions shared reduced rsFC with bilateral hippocampal/parahippocampal gyri (HG/PHG) but also showed distinct changes, including reduced vVS rsFC with ventromedial prefrontal cortex (vmPFC) and increased daVS rsFC with visual cortex in CD as compared to HC. Across CD, daVS visual cortical connectivity was positively correlated with amount of prior-month cocaine use and cocaine craving, and vVS vmPFC connectivity was negatively correlated with the extent of depression and anxiety. These findings suggest a distinct pattern of altered VS subregional rsFC in cocaine dependence, and some of the changes have eluded analyses using the whole VS as a seed region. The findings may provide new insight to delineating VS circuit deficits in cocaine dependence and provide an alternative analytical framework to address functional dysconnectivity in other mental illnesses.

Effect of smoking on resting-state functional connectivity in smokers: An fMRI study.

Smoking is a leading cause of death in the world. Aberrant brain function has been repeatedly linked to tobacco smoking. However, little is known about insula-based resting-state functional connectivity (rsFC) in non-deprived tobacco-dependent smokers. This study characterized the correlation between insula-based rsFC and tobacco dependence severity in non-deprived smokers. A total of 37 male smokers and 37 age-matched male non-smokers completed resting-state functional MRI (fMRI) scans. The insula-based rsFC differences between smokers and controls were investigated and the correlation between insula-based rsFC and FTND (Fagerström Test for Nicotine Dependence) scores were then assessed. Compared with controls, smokers showed significantly lower rsFC between orbitofrontal cortex, superior frontal gyrus, temporal lobe and insula. The rsFC between orbitofrontal cortex, temporal lobe, inferior parietal cortex, occipital lobe and insula was positively correlated with FTND. However, the rsFC between anterior cingulate cortex and insula was negatively correlated with FTND. Our findings suggest differences in brain functional connectivity between smokers and non-smokers. This study sheds new insights into the neural mechanisms of tobacco dependence.