Positive Functional Connectivity Research Articles

The functional connectivity of the right superior temporal gyrus is associated with psychological risk and resilience factors for suicidality

IntroductionSuicide attempters show increased activation in the right superior temporal gyrus (rSTG). Here, we investigated the rSTG functional connectivity (FC) to identify a functional network involved in suicidality and its associations with psychological suicidality risk and resilience factors. MethodsThe resting state functional magnetic resonance imaging data of 151 healthy individuals from the Human Connectome Project Young Adult database were used to explore the FC of the rSTG with itself and with the rest of the brain. The correlation between the rSTG FC and loneliness and purpose in life scores was assessed with the NIH Toolbox. The effect of sex was also investigated. ResultsThe rSTG had a positive FC with bilateral cortical and subcortical regions, including frontal, temporal, parietal, occipital, limbic, and cerebellar regions, and a negative FC with the medulla oblongata. The FC of the rSTG with itself and with the left central operculum were associated with loneliness scores. The within rSTG FC was also negatively correlated with purpose in life scores, although at a trend level. We did not find any effect of sex on FC and its associations with psychological factors. LimitationsThe cross-sectional design, the limited age range, and the lack of measures of suicidality limit the generalizability of our findings. ConclusionsThe rSTG functional network is associated with loneliness and purpose in life. Together with the existing literature on suicide, this supports the idea that the neural activity of rSTG may contribute to suicidality by modulating risk and resilience factors associated with suicidality.

Dynamic graph transformer network via dual-view connectivity for autism spectrum disorder identification

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that requires objective and accurate identification methods for effective early intervention. Previous population-based methods via functional connectivity (FC) analysis ignore the differences between positive and negative FCs, which provide the potential information complementarity. And they also require additional information to construct a pre-defined graph. Meanwhile, two challenging demand attentions are the imbalance of performance caused by the class distribution and the inherent heterogeneity of multi-site data. In this paper, we propose a novel dynamic graph Transformer network based on dual-view connectivity for ASD Identification. It is based on the Autoencoders, which regard the input feature as individual feature and without any inductive bias. First, a dual-view feature extractor is designed to extract individual and complementary information from positive and negative connectivity. Then Graph Transformer network is innovated with a hot plugging K-Nearest Neighbor (KNN) algorithm module which constructs a dynamic population graph without any additional information. Additionally, we introduce the PolyLoss function and the Vrex method to address the class imbalance and improve the model's generalizability. The evaluation experiment on 1102 subjects from the ABIDE I dataset demonstrates our method can achieve superior performance over several state-of-the-art methods and satisfying generalizability for ASD identification.

Perceiving humanness across ages: neural correlates and behavioral patterns.

Humanness perception, which attributes fundamental and unique human characteristics to other objects or people, has significant consequences for people's interactions. Notably, the failure to perceive humanness in older adults can lead to prejudice. This study investigates the effect of a target's age on humanness perception in terms of two dimensions: agency (the ability to act and do) and experience (the ability to feel and sense). We also examined brain activity using a magnetic resonance imaging (MRI) scanner in order to understand the underlying neural mechanisms. Healthy university students viewed the facial images of older and younger individuals and judged the humanness of each individual in terms of agency and experience while inside the MRI scanner. The results indicated that older adults were rated higher on experience, and no difference was found in ratings for agency between younger and older face images. Analysis of brain imaging data indicated that positive functional connectivity between the ventral and dorsal regions of the medial prefrontal cortex (mPFC) was greater when judging the humanness of younger faces than older faces. We also found that the negative functional connectivity between the left inferior frontal gyrus and postcentral gyrus was greater when judging the humanness of older faces as compared to that of younger faces. Although the current study did not show distinct brain activities related to humanness perception, it suggests the possibility that different brain connectivities are related to humanness perception regarding targets belonging to different age groups.

Differential functional organization of amygdala-medial prefrontal cortex networks in macaque and human

Over the course of evolution, the amygdala (AMG) and medial frontal cortex (mPFC) network, involved in behavioral adaptation, underwent structural changes in the old-world monkey and human lineages. Yet, whether and how the functional organization of this network differs remains poorly understood. Using resting-state functional magnetic resonance imagery, we show that the functional connectivity (FC) between AMG nuclei and mPFC regions differs between humans and awake macaques. In humans, the AMG-mPFC FC displays U-shaped pattern along the corpus callosum: a positive FC with the ventromedial prefrontal (vmPFC) and anterior cingulate cortex (ACC), a negative FC with the anterior mid-cingulate cortex (MCC), and a positive FC with the posterior MCC. Conversely, in macaques, the negative FC shifted more ventrally at the junction between the vmPFC and the ACC. The functional organization divergence of AMG-mPFC network between humans and macaques might help understanding behavioral adaptation abilities differences in their respective socio-ecological niches.

Increased interhemispheric functional connectivity after right anodal tDCS in chronic non-fluent aphasia: preliminary findings.

Anodal transcranial Direct Current Stimulation (tDCS) is a non-invasive, low-cost and environment-friendly brain neuromodulation technique that increases cortical excitability. In post-stroke aphasia, the role of the right hemisphere in language recovery remains debated. In this preliminary study, we aimed to investigate the efficacy of excitatory tDCS on the right hemisphere in chronic aphasic patients. We applied anodal tDCS to the right homologous region of Broca's area in four chronic aphasic patients while performing a one-month naming rehabilitation treatment. Longitudinal data on language assessment and naming performance were collected. Resting-state fMRI images were acquired before and after treatment to measure changes in functional connectivity. Results showed enhanced positive functional connectivity of the right Broca homologous with the left middle frontal and middle temporal gyri. Every patient showed improvements in language functions, but no major changes in naming performance. These preliminary findings suggest that tDCS applied over the unaffected hemisphere may result in longitudinal inter-hemispheric functional neuroplastic changes that could specifically improve language recovery and could potentially be included in therapeutic neurorehabilitative plans.

Early life stress and body-mass-index modulate brain connectivity in alcohol use disorder

Early life stress (ELS) significantly increases susceptibility to alcohol use disorder (AUD) by affecting the interplay between the executive and the salience networks (SNs). The link between AUD and higher body-mass index (BMI) is known, but we lack understanding of how BMI impacts the relationship between ELS and brain connectivity in individuals with AUD. To bridge this gap, we investigated the main and interaction effects of ELS and BMI on brain connectivity in individuals with AUD compared to non-AUD participants (n = 77 sex-matched individuals per group). All participants underwent resting-state functional magnetic resonance imaging, revealing intriguing positive functional connectivity between SN seeds and brain regions involved in somatosensory processing, motor coordination and executive control. Examining the relationship of brain connectivity with ELS and BMI, we observed positive associations with the correlations of SN seeds, right anterior insula (RAIns) and supramarginal gyrus (SMG) with clusters in motor [occipital cortex, supplementary motor cortex]; anterior cingulate cortex (ACC) with clusters in frontal, or executive, control regions (middle frontal gyrus; MFG, precentral gyrus) that reportedly are involved in processing of emotionally salient stimuli (all |β | > 0.001, |p | < 0.05). Interestingly, a negative association of the interaction effect of ELS events and BMI measures with the functional connectivity of SN seeds ACC with decision-making (MFG, precentral gyrus), RAIns and RSMG with visuo-motor control regions (occipital cortex and supplementary motor cortex) (all |β | = −0.001, |p | < 0.05). These findings emphasize the moderating effect of BMI on ELS-associated SN seed brain connectivity in AUD. Understanding the neural mechanisms linking BMI, ELS and AUD can guide targeted interventions for this population.

Aberrant resting-state functional connectivity of the globus pallidus interna in first-episode schizophrenia.

The striatal-pallidal pathway plays an important role in cognitive control and modulation of behaviors. Globus pallidus interna (GPi), as a primary output structure, is crucial in modulating excitation and inhibition. Studies of GPi in psychiatric illnesses are lacking given the technical challenges of examining this small and functionally diverse subcortical structure. 71 medication-naïve first episode schizophrenia (FES) participants and 73 healthy controls (HC) were recruited at the Shanghai Mental Health Center. Clinical symptoms and imaging data were collected at baseline and, in a subset of patients, 8weeks after initiating treatment. Resting-state functional connectivity of sub-regions of the GP were assessed using a novel mask that combines two atlases to create 8 ROIs in the GP. Baseline imaging data from 63 FES patients and 55 HC met quality standards and were analyzed. FES patients exhibited less negative connectivity and increased positive connectivity between the right anterior GPi and several cortical and subcortical areas at baseline compared to HC (PFWE<0.05). Positive functional connectivity between the right anterior GPi and several brain areas, including the right dorsal anterior cingulate gyrus, was associated with severity of positive symptoms (PFWE<0.05) and predicted treatment response after 8weeks (n=28, adjusted R2=0.486, p<0.001). Our results implicate striatal-pallidal-thalamic pathways in antipsychotic efficacy. If replicated, these findings may reflect failure of neurodevelopmental processes in adolescence and early adulthood that decrease functional connectivity as an index of failure of the limbic/associative GPi to appropriately inhibit irrelevant signals in psychosis.

Altered functional connectivity of the hippocampus with the sensorimotor cortex induced by long-term experience of virtual hand illusion

Synchronizing the movement of a virtual hand with an unseen real hand in a virtual environment is an effective method to induce a sense of ownership of the virtual hand. Although several neuroimaging studies have revealed neural mechanisms related to the ongoing process of ownership illusion, the effect of the long-term experience of ownership illusion on brain activity remains to be investigated. Here, we developed an apparatus based on real-time image matting and virtual reality technology which allowed us to use the image of participants’ real hands as their virtual hands and synchronize the movement of the virtual hands with the unseen real hands in a virtual scene. Resting-state functional imaging data were acquired immediately after participants completed several light office tasks with the virtual hands in either the virtual environment (virtual hand condition) or real environment (real hand condition). Significant positive functional connectivity of the hippocampus with the primary somatosensory and motor cortex was only observed in the virtual hand condition. The results provided novel evidence for the involvement of hippocampal-sensorimotor connection in the long-term experience of virtual hand ownership. The functional connection reorganization of the hippocampus might promote multi-sensory information integration into memory and updated the sense of body ownership, which offered important insights into the neural network underlying the availability of long-term use of VR technology in healthcare and rehabilitation.

Urinary incontinence-related effects on functional connectivity circuits in persons with Parkinson's disease.

Urinary incontinence (UI) is a common and disruptive symptom of Parkinson's disease (PD). This study aimed to identify neural correlates associated with UI among PD patients with UI (UI-PD) compared to those PD patients without UI (nonUI-PD) with the expectation of demonstrating increased functional connectivity (FC) between areas in the striatum and limbic system and decreased FC in executive areas. rsfMRI and T1w data (n = 119) were retrieved from the Parkinson's Progression Markers Initiative (PPMI). Resting-state FC analyses assessed temporal covariance with anterior cingulate gyrus, precuneus, and putamen seed regions. The UI-PD group (n = 32, 16 females) showed significantly greater positive FC between the bilateral putamen seed and the right caudate and right thalamus (p < 0.01), relative to individuals with PD but who did not have UI (n = 87, 18 females). The UI-PD group showed greater negative FC between the anterior cingulate seed and right angular gyrus (p < 0.01) relative to nonUI-PD. Individuals with PD and UI display stronger FC within neural circuits likely affected by PD such as between the putamen and caudate, as well as within those associated with brain bladder control, compared to persons with PD and without UI. Clinical application based on this study's results can provide greater discernment of treatment strategies for UI-PD patients.

Dynamic interactions between anterior insula and anterior cingulate cortex link perceptual features and heart rate variability during movie viewing.

The dynamic integration of sensory and bodily signals is central to adaptive behaviour. Although the anterior cingulate cortex (ACC) and the anterior insular cortex (AIC) play key roles in this process, their context-dependent dynamic interactions remain unclear. Here, we studied the spectral features and interplay of these two brain regions using high-fidelity intracranial-EEG recordings from five patients (ACC: 13 contacts, AIC: 14 contacts) acquired during movie viewing with validation analyses performed on an independent resting intracranial-EEG dataset. ACC and AIC both showed a power peak and positive functional connectivity in the gamma (30-35 Hz) frequency while this power peak was absent in the resting data. We then used a neurobiologically informed computational model investigating dynamic effective connectivity asking how it linked to the movie's perceptual (visual, audio) features and the viewer's heart rate variability (HRV). Exteroceptive features related to effective connectivity of ACC highlighting its crucial role in processing ongoing sensory information. AIC connectivity was related to HRV and audio emphasising its core role in dynamically linking sensory and bodily signals. Our findings provide new evidence for complementary, yet dissociable, roles of neural dynamics between the ACC and the AIC in supporting brain-body interactions during an emotional experience.

Associations between infant amygdala functional connectivity and social engagement following a stressor: A preliminary investigation.

Functional architecture of the infant brain, especially functional connectivity (FC) within the amygdala network and between the amygdala and other networks (i.e., default-mode [DMN] and salience [SAL] networks), provides a neural basis for infant socioemotional functioning. Yet, little is known about the extent to which early within- and between-network amygdala FC are related to infant stress recovery across the first year of life. In this study, we examined associations between amygdala FC (i.e., within-network amygdala connectivity, and between-network amygdala connectivity with the DMN and SAL) at 3 months and infant recovery from a mild social stressor at 3, 6 and 9 months. At 3 months, thirty-five infants (13 girls) underwent resting-state functional magnetic resonance imaging during natural sleep. Infants and their mothers completed the still-face paradigm at 3, 6, and 9 months, and infant stress recovery was assessed at each time point as the proportion of infant social engagement during the reunion episode. Bivariate correlations indicated that greater positive within-network amygdala FC and greater positive amygdala-SAL FC, but not amygdala-DMN FC, at 3 months predicted lower levels of stress recovery at 3 and 6 months, but were nonsignificant at 9 months. These findings provide preliminary evidence that early functional synchronization within the amygdala network, as well as segregation between the amygdala and the SAL, may contribute to infant stress recovery in the context of infant-mother interaction.

Maternal education as an environmental factor related to reading in children with reading difficulties: A functional magnetic resonance imaging study.

The expanded simple view of reading (SVR) model suggests that word decoding, language comprehension and executive functions are necessary for reading comprehension. Children with reading difficulties (RDs) often have deficits in critical components of reading established in the expanded SVR model and alterations in brain function of reading-related regions. Maternal education could provide children with advantageous educational opportunities or resources that support reading acquisition. The primary goal of this study was to examine the contributions of maternal education to the behavioural and neurobiological correlates of the expanded SVR model. Seventy-two 8- to 12-year-old children with RDs and typical readers (TRs) completed reading, behavioural and an functional magnetic resonance imaging stories-listening task to determine the functional connectivity of the receptive language network to the whole brain in association with maternal education. Higher maternal education was associated with better vocabulary in children with RDs and positive functional connectivity between the receptive language network and regions related to visual processing in children with RDs versus TRs. These data suggest that maternal education supports the ability to comprehend oral language and engagement of neural networks that support imagination/visualization in children with RDs.

Alterations in Dynamic Functional Connectivity in Patients with Cerebral Small Vessel Disease

Cerebral small vessel disease (CSVD) is a common disease that seriously endangers people’s health, and is easily overlooked by both patients and clinicians due to its near-silent onset. Dynamic functional connectivity (DFC) is a new concept focusing on the dynamic features and patterns of brain networks that represents a powerful tool for gaining novel insight into neurological diseases. To assess alterations in DFC in CSVD patients, and the correlation of DFC with cognitive function. We enrolled 35 CSVD patients and 31 normal control subjects (NC). Resting-state functional MRI (rs-fMRI) with a sliding-window approach and k-means clustering based on independent component analysis (ICA) was used to evaluate DFC. The temporal properties of fractional windows and the mean dwell time in each state, as well as the number of transitions between each pair of DFC states, were calculated. Additionally, we assessed the functional connectivity (FC) strength of the dynamic states and the associations of altered neuroimaging measures with cognitive performance. A dynamic analysis of all included subjects suggested four distinct functional connectivity states. Compared with the NC group, the CSVD group had more fractional windows and longer mean dwell times in state 4 characterized by sparse FC both inter-network and intra-networks. Additionally, the CSVD group had a reduced number of windows and shorter mean dwell times compared to the NC group in state 3 characterized by highly positive FC between the somatomotor and visual networks, and negative FC in the basal ganglia and somatomotor and visual networks. The number of transitions between state 2 and state 3 and between state 3 and state 4 was significantly reduced in the CSVD group compared to the NC group. Moreover, there was a significant difference in the FC strength between the two groups, and the altered temporal properties of DFC were significantly related to cognitive performance. Our study indicated that CSVD is characterized by altered temporal properties in DFC that may be sensitive neuroimaging biomarkers for early disease identification. Further study of DFC alterations could help us to better understand the progressive dysfunction of networks in CSVD patients.

Task-based functional connectivity reveals aberrance with the salience network during emotional interference in late-life depression

Objectives Late-life depression (LLD) is a common and debilitating disorder. Previously, resting-state studies have revealed abnormal functional connectivity (FC) of brain networks in LLD. Since LLD is associated with emotional-cognitive control deficits, the aim of this study was to compare FC of large-scale brain networks in older adults with and without a history of LLD during a cognitive control task with emotional stimuli. Methods Cross-sectional case-control study. Twenty participants diagnosed with LLD and 37 never-depressed adults 60–88 years of age underwent functional magnetic resonance imaging during an emotional Stroop task. Network-region-to-region FC was assessed with seed regions in the default mode, the frontoparietal, the dorsal attention, and the salience networks. Results FC between salience and sensorimotor network regions and between salience and dorsal attention network regions were reduced in LLD patients compared to controls during the processing of incongruent emotional stimuli. The normally positive FC between these networks were negative in LLD patients and inversely correlated with vascular risk and white matter hyperintensities. Conclusions Emotional-cognitive control in LLD is associated with aberrant functional coupling between salience and other networks. This expands on the network-based LLD model and proposes the salience network as a target for future interventions.

Altered patterns of central executive, default mode and salience network activity and connectivity are associated with current and future depression risk in two independent young adult samples.

Neural markers of pathophysiological processes underlying the dimension of subsyndromal-syndromal-level depression severity can provide objective, biologically informed targets for novel interventions to help prevent the onset of depressive and other affective disorders in individuals with subsyndromal symptoms, and prevent worsening symptom severity in those with these disorders. Greater functional connectivity (FC) among the central executive network (CEN), supporting emotional regulation (ER) subcomponent processes such as working memory (WM), the default mode network (DMN), supporting self-related information processing, and the salience network (SN), is thought to interfere with cognitive functioning and predispose to depressive disorders. We examined in young adults (1) relationships among activity and FC in these networks and current depression severity, using a paradigm designed to examine WM and ER capacity in n = 90, age = 21.7 (2.0); (2) the extent to which these relationships were specific to depression versus mania/hypomania; (3) whether findings in a first, "discovery" sample could be replicated in a second, independent, "test" sample of young adults n = 96, age = 21.6 (2.1); and (4) whether such relationships also predicted depression at up to 12 months post scan and/or mania/hypomania severity in (n = 61, including participants from both samples, age = 21.6 (2.1)). We also examined the extent to which there were common depression- and anxiety-related findings, given that depression and anxiety are highly comorbid. In the discovery sample, current depression severity was robustly predicted by greater activity and greater positive functional connectivity among the CEN, DMN, and SN during working memory and emotional regulation tasks (all ps < 0.05 qFDR). These findings were specific to depression, replicated in the independent sample, and predicted future depression severity. Similar neural marker-anxiety relationships were shown, with robust DMN-SN FC relationships. These data help provide objective, neural marker targets to better guide and monitor early interventions in young adults at risk for, or those with established, depressive and other affective disorders.

Dissociation of categorical and coordinate spatial relations on dynamic network organization states.

Humans can flexibly represent both categorical and coordinate spatial relations. Previous research has mainly focused on hemisphere lateralization in representing these two types of spatial relations, but little is known about how distinct network organization states support representations of the two. Here we used dynamic resting-state functional connectivity (FC) to explore this question. To do this, we separated a meta-identified navigation network into a ventral and two other subnetworks. We revealed a Weak State and a Strong State within the ventral subnetwork and a Negative State and a Positive State between the ventral and other subnetworks. Further, we found the Weak State (i.e., weak but positive FC) within the ventral subnetwork was related to the ability of categorical relation recognition, suggesting that the representation of categorical spatial relations was related to weak integration among focal regions in the navigation network. In contrast, the Negative State (i.e., negative FC) between the ventral and other subnetworks was associated with the ability of coordinate relation processing, suggesting that the representation of coordinate spatial relations may require competitive interactions among widely distributed regions. In sum, our study provides the first empirical evidence revealing different focal and distributed organizations of the navigation network in representing different types of spatial information.

Anatomical distance affects functional connectivity at rest in medicine-free obsessive–compulsive disorder

BackgroundBrain functional abnormalities at rest have been observed in obsessive–compulsive disorder (OCD). However, whether and how anatomical distance influences functional connectivity (FC) at rest is ambiguous in OCD.MethodsUsing resting-state functional magnetic resonance imaging data, we calculated the FC of each voxel in the whole-brain and divided FC into short- and long-range FCs in 40 medicine-free patients with OCD and 40 healthy controls (HCs). A support vector machine (SVM) was used to determine whether the altered short- and long-range FCs could be utilized to distinguish OCD from HCs.ResultsPatients had lower short-range positive FC (spFC) and long-range positive FC (lpFC) in the left precentral/postcentral gyrus (t = -5.57 and -5.43; P < 0.05, GRF corrected) and higher lpFC in the right thalamus/caudate, left thalamus, left inferior parietal lobule (IPL) and left cerebellum CrusI/VI (t = 4.59, 4.61, 4.41, and 5.93; P < 0.05, GRF corrected). Furthermore, lower spFC in the left precentral/postcentral gyrus might be used to distinguish OCD from HCs with an accuracy of 80.77%, a specificity of 81.58%, and a sensitivity of 80.00%.ConclusionThese findings highlight that anatomical distance has an effect on the whole-brain FC patterns at rest in OCD. Meanwhile, lower spFC in the left precentral/postcentral gyrus might be applied in distinguishing OCD from HCs.

Abnormal long- and short-range functional connectivity in patients with first-episode drug-naïve melancholic and non-melancholic major depressive disorder

BackgroundWe attempted to explore the common and distinct long- and short-range functional connectivity (FC) patterns of melancholic and non-melancholic major depressive disorder (MDD) and their associations with clinical characteristics. MethodsFifty-nine patients with first-episode drug-naïve MDD, including 31 patients with melancholic features and 28 patients with non-melancholic features, underwent resting-state functional magnetic resonance imaging (fMRI) scanning to examine long- and short-range FC. Thirty-two healthy volunteers were recruited as controls. The support vector machines (SVM) was applied to distinguish the melancholic patients from the non-melancholic patients by using the FC of abnormal brain regions. ResultsCompared to healthy volunteers, patients with MDD showed increased long-range positive FC (lpFC) in the right insula/inferior frontal gyrus and left insula. Relative to non-melancholic patients, melancholic patients displayed decreased lpFC in the right lingual gyrus, decreased short-range positive FC (spFC) in the right middle temporal gyrus and right superior parietal lobule, increased lpFC in the left inferior parietal lobule, and increased spFC in the left middle occipital gyrus/inferior occipital gyrus, left cerebellum VII/IX, and bilateral cerebellum CrusII. Increased lpFC in the left inferior parietal lobule in melancholic patients was correlated with the TEPS abstract anticipatory scores. SVM results showed that FCs of five combinations within different brain regions could distinguish melancholic patients from non-melancholic patients. ConclusionsFC abnormalities in the default mode network and parietal-occipital brain regions may underlie the neurobiology of melancholic MDD. An increased lpFC in the left inferior parietal lobule correlated with anhedonia may be a distinctive neurobiological feature of melancholic MDD.

Neural underpinnings of expecting alcohol: Placebo alcohol administration alters nucleus accumbens resting state functional connectivity

BackgroundUsing balanced placebo designs, seminal alcohol administration research has shown individuals’ beliefs about whether they have consumed alcohol, irrespective of the actual presence of alcohol, can determine level of alcohol consumption and impact social behavior. Despite the known effect of expecting alcohol on drinking behavior, few studies have used the placebo manipulation to directly investigate the neural underpinnings of the expectancy-related effects that occur following perceived alcohol consumption in humans. The present paper examined placebo responses in the laboratory to better understand the neural basis for the psychological phenomenon of expectancies. MethodsAs part of a larger within-subjects study design, healthy young adults (N = 22, agemean+SD=23 +1) completed resting state fMRI scans and measures of subjective response before and after consuming placebo beverages. Effect of placebo beverage consumption (pre- versus post-beverage consumption) on functional connectivity within prefrontal cortical networks was examined using the CONN Toolbox. Relations between perceived subjective response to alcohol with functional connectivity response following placebo beverage consumption were examined. ResultsCompared to pre-beverage scan, placebo beverage consumption was associated with increased positive functional connectivity between right nucleus accumbens – ventromedial prefrontal cortex and subcallosal cingulate cortex (pFDR<0.05). Subjective ratings of intoxication (i.e., feeling ‘drunk’) positively correlated with placebo beverage-related increases in nucleus accumbens – subcallosal cingulate cortex functional connectivity. ConclusionResults suggest placebo response to alcohol is associated with increased functional connectivity within a key reward network (nucleus accumbens – ventromedial prefrontal cortex and subcallosal cingulate cortex) and put forth a mechanism by which alcohol expectancies may contribute to the subjective experience of intoxication.

Functional connectivity in reward circuitry and symptoms of anhedonia as therapeutic targets in depression with high inflammation: evidence from a dopamine challenge study

Increased inflammation in major depressive disorder (MDD) has been associated with low functional connectivity (FC) in corticostriatal reward circuits and symptoms of anhedonia, relationships which may involve the impact of inflammation on synthesis and release of dopamine. To test this hypothesis while establishing a platform to examine target engagement of potential therapies in patients with increased inflammation, medically stable unmedicated adult MDD outpatients enrolled to have a range of inflammation (as indexed by plasma C-reactive protein [CRP] levels) were studied at two visits involving acute challenge with the dopamine precursor levodopa (L-DOPA; 250 mg) and placebo (double-blind, randomized order ~1-week apart). The primary outcome of resting-state (rs)FC in a classic ventral striatum to ventromedial prefrontal cortex reward circuit was calculated using a targeted, a priori approach. Data available both pre- and post-challenge (n = 31/40) established stability of rsFC across visits and determined CRP > 2 mg/L as a cut-point for patients exhibiting positive FC responses (post minus pre) to L-DOPA versus placebo (p < 0.01). Higher post-L-DOPA FC in patients with CRP > 2 mg/L was confirmed in all patients (n = 40) where rsFC data were available post-challenge (B = 0.15, p = 0.006), and in those with task-based (tb)FC during reward anticipation (B = 0.15, p = 0.013). While effort-based motivation outside the scanner positively correlated with rsFC independent of treatment or CRP, change in anhedonia scores negatively correlated with rsFC after L-DOPA only in patients with CRP > 2 mg/L (r = -0.56, p = 0.012). FC in reward circuitry should be further validated in larger samples as a biomarker of target engagement for potential treatments including dopaminergic agents in MDD patients with increased inflammation.