Differences In Resting-state Functional Connectivity Research Articles

Gender differences in the functional language networks at birth: a resting-state fNIRS study.

Numerous studies reported inconsistent results concerning gender influences on the functional organization of the brain for language in children and adults. However, data for the gender differences in the functional language networks at birth are sparse. Therefore, we investigated gender differences in resting-state functional connectivity in the language-related brain regions in newborns using functional near-infrared spectroscopy. The results revealed that female newborns demonstrated significantly stronger functional connectivities between the superior temporal gyri and middle temporal gyri, the superior temporal gyri and the Broca's area in the right hemisphere, as well as between the right superior temporal gyri and left Broca's area. Nevertheless, statistical analysis failed to reveal functional lateralization of the language-related brain areas in resting state in both groups. Together, these results suggest that the onset of language system might start earlier in females, because stronger functional connectivities in the right brain in female neonates were probably shaped by the processing of prosodic information, which mainly constitutes newborns' first experiences of speech in the womb. More exposure to segmental information after birth may lead to strengthened functional connectivities in the language system in both groups, resulting in a stronger leftward lateralization in males and a more balanced or leftward dominance in females.

Short communication: Lifetime musical activity and resting-state functional connectivity in cognitive networks.

Participation in multimodal leisure activities, such as playing a musical instrument, may be protective against brain aging and dementia in older adults (OA). Potential neuroprotective correlates underlying musical activity remain unclear. This cross-sectional study investigated the association between lifetime musical activity and resting-state functional connectivity (RSFC) in three higher-order brain networks: the Default Mode, Fronto-Parietal, and Salience networks. We assessed 130 cognitively unimpaired participants (≥ 60 years) from the baseline cohort of the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Lifetime musical activity was operationalized by the self-reported participation in musical instrument playing across early, middle, and late life stages using the Lifetime of Experiences Questionnaire (LEQ). Participants who reported musical activity during all life stages (n = 65) were compared to controls who were matched on demographic and reserve characteristics (including education, intelligence, socioeconomic status, self-reported physical activity, age, and sex) and never played a musical instrument (n = 65) in local (seed-to-voxel) and global (within-network and between-network) RSFC patterns using pre-specified network seeds. Older participants with lifetime musical activity showed significantly higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal as well as frontal regions, namely the right temporal pole and the right precentral gyrus extending into the superior frontal gyrus, compared to matched controls. There were no significant group differences in global RSFC within or between the three networks. We show that playing a musical instrument during life relates to higher RSFC of the medial prefrontal cortex with distant brain regions involved in higher-order cognitive and motor processes. Preserved or enhanced functional connectivity could potentially contribute to better brain health and resilience in OA with a history in musical activity. German Clinical Trials Register (DRKS00007966, 04/05/2015).

Effects of bilateral tDCS over DLPFC on response inhibition, craving, and brain functional connectivity in Internet gaming disorder: Arandomized, double-blind, sham-controlled trial with fMRI.

Impaired inhibitory control accompanied by enhanced craving is hallmark of addiction. This study investigated the effects of transcranial direct current stimulation (tDCS) on response inhibition and craving in Internet gaming disorder (IGD). We examined the brain changes after tDCS and their correlation with clinical variables. Twenty-four males with IGD were allocated randomly to an active or sham tDCS group, and data from 22 participants were included for analysis. Participants self-administered bilateral tDCS over the dorsolateral prefrontal cortex (DLPFC) for 10 sessions. Stop-signal tasks were conducted to measure response inhibition and participants were asked about their cravings for Internet gaming at baseline and post-tDCS. Functional magnetic resonance imaging data were collected at pre- and post-tDCS, and group differences in resting-state functional connectivity (rsFC) changes from the bilateral DLPFC and nucleus accumbens were examined. We explored the relationship between changes in the rsFC and behavioral variables in the active tDCS group. A significant group-by-time interaction was observed in response inhibition. After tDCS, only the active group showed a decrease in the stop-signal reaction time (SSRT). Although craving decreased, there were no significant group-by-time interactions or group main effects. The anterior cingulate cortex (ACC) showed group differences in post- versus pre-tDCS rsFC from the right DLPFC. The rsFC between the ACC and left middle frontal gyrus was negatively correlated with the SSRT. Our study provides preliminary evidence that bilateral tDCS over the DLPFC improves inhibitory control and could serve as a therapeutic approach for IGD.

Resting-state Functional Connectivity of the Motor and Cognitive Areas is Preserved in Masters Athletes

Aging is characterized by a decline in physical and cognitive functions, often resulting in decreased quality of life. Physical activity has been suggested to potentially slow down various aspects of the aging process, a theory that has been supported by studies of Masters Athletes (MA). For example, MA usually have better cognitive and physical functions than age-matched sedentary and healthy older adults (OA), making them a valuable model to gain insights into mechanisms that promote physical and cognitive function with aging. The purpose of this study was to identify differences in resting-state functional connectivity (rs-FC) of motor and cognitive regions between MA and OA and determine if these differences in the resting brain are associated with differences in cognitive and physical performance between groups. Fifteen MA (9 males) and 12 age-matched OA (six males) were included. rs-FC images were compared to identify significant between-groups differences in brain connectivity. There was higher connectivity between the cognitive and motor networks for the OA group, whereas the MA group had stronger connectivity between different regions within the same network, both for the cognitive and the motor networks. These results are in line with the literature suggesting that aging reduces the segregation between functional networks and causes regions within the same network to be less strongly connected. High-level physical activity practiced by the MA most likely contributes to attenuating aging-related changes in brain functional connectivity, preserving clearer boundaries between different functional networks, which may ultimately favor maintenance of efficient cognitive and sensorimotor processing.

Altered resting-state functional connectivity and dynamic network properties in cognitive impairment: an independent component and dominant-coactivation pattern analyses study.

Cognitive impairment (CI) due to Alzheimer's disease (AD) encompasses a decline in cognitive abilities and can significantly impact an individual's quality of life. Early detection and intervention are crucial in managing CI, both in the preclinical and prodromal stages of AD prior to dementia. In this preliminary study, we investigated differences in resting-state functional connectivity and dynamic network properties between 23 individual with CI due to AD based on clinical assessment and 15 healthy controls (HC) using Independent Component Analysis (ICA) and Dominant-Coactivation Pattern (d-CAP) analysis. The cognitive status of the two groups was also compared, and correlations between cognitive scores and d-CAP switching probability were examined. Results showed comparable numbers of d-CAPs in the Default Mode Network (DMN), Executive Control Network (ECN), and Frontoparietal Network (FPN) between HC and CI groups. However, the Visual Network (VN) exhibited fewer d-CAPs in the CI group, suggesting altered dynamic properties of this network for the CI group. Additionally, ICA revealed significant connectivity differences for all networks. Spatial maps and effect size analyses indicated increased coactivation and more synchronized activity within the DMN in HC compared to CI. Furthermore, reduced switching probabilities were observed for the CI group in DMN, VN, and FPN networks, indicating less dynamic and flexible functional interactions. The findings highlight altered connectivity patterns within the DMN, VN, ECN, and FPN, suggesting the involvement of multiple functional networks in CI. Understanding these brain processes may contribute to developing targeted diagnostic and therapeutic strategies for CI due to AD.

Data-driven connectivity profiles relate to smoking cessation outcomes.

At a group level, nicotine dependence is linked to differences in resting-state functional connectivity (rs-FC) within and between three large-scale brain networks: the salience network (SN), default mode network (DMN), and frontoparietal network (FPN). Yet, individuals may display distinct patterns of rs-FC that impact treatment outcomes. This study used a data-driven approach, Group Iterative Multiple Model Estimation (GIMME), to characterize shared and person-specific rs-FC features linked with clinically-relevant treatment outcomes. 49 nicotine-dependent adults completed a resting-state fMRI scan prior to a two-week smoking cessation attempt. We used GIMME to identify group, subgroup, and individual-level networks of SN, DMN, and FPN connectivity. Regression models assessed whether within- and between-network connectivity of individual rs-FC models was associated with baseline cue-induced craving, and craving and use of regular cigarettes (i.e., "slips") during cessation. As a group, participants displayed shared patterns of connectivity within all three networks, and connectivity between the SN-FPN and DMN-SN. However, there was substantial heterogeneity across individuals. Individuals with greater within-network SN connectivity experienced more slips during treatment, while individuals with greater DMN-FPN connectivity experienced fewer slips. Individuals with more anticorrelated DMN-SN connectivity reported lower craving during treatment, while SN-FPN connectivity was linked to higher craving. In conclusion, in nicotine-dependent adults, GIMME identified substantial heterogeneity within and between the large-scale brain networks. Individuals with greater SN connectivity may be at increased risk for relapse during treatment, while a greater positive DMN-FPN and negative DMN-SN connectivity may be protective for individuals during smoking cessation treatment.

Resting state functional connectivity differences following working memory training with massed exposure in individuals with public speaking anxiety

Exposure-based cognitive behavioral therapy (CBT) is a gold standard treatment for Social Anxiety Disorder (SAD), but many patients do not gain complete symptom relief. Since fear extinction is central to the effectiveness of exposure within CBT, adjunctive treatments that target neurocognitive systems underlying fear extinction could increase the effectiveness of CBT. Successful fear extinction and cognitive tasks like working memory share neurocognitive substrates. The present study evaluates the neural impact of working memory training (WMT) as an adjunctive CBT treatment by exploring changes in intrinsic network connectivity associated with combining WMT with exposure exercises. The sample included twenty-four adults (Mean Age = 27.42(9.75), 62.5% female) with elevated social anxiety symptoms. Participants completed either a WMT or sham training (ST) condition, followed by a speech-based massed exposure session (WMT+Exp versus ST+Exp). Compared to ST+Exp, WMT+Exp participants exhibited lower connectivity between the default and visual networks and visual and dorsal networks. Lower connectivity between these networks was associated with lower subjective distress at the end of the massed exposure across the whole sample. WMT+Exp completers exhibited unique functional connectivity between the frontoparietal and dorsal attention networks. WM+Exp was associated with a neural connectivity profile involving networks critical to working memory, fear learning, and emotion regulation, as well as emotional and sensory processing functions. Data provisionally point to combined working memory training and exposure facilitating improvement in neural connections useful for benefitting from CBT for SAD.

Network-based statistics distinguish anomic and Broca's aphasia.

Aphasia is a speech-language impairment commonly caused by damage to the left hemisphere. The neural mechanisms that underpin different types of aphasia and their symptoms are still not fully understood. This study aims to identify differences in resting-state functional connectivity between anomic and Broca's aphasia measured through resting-state functional magnetic resonance imaging (rs-fMRI). We used the network-based statistic (NBS) method, as well as voxel- and connectome-based lesion symptom mapping (V-, CLSM), to identify distinct neural correlates of the anomic and Broca's groups. To control for lesion effect, we included lesion volume as a covariate in both the NBS method and LSM. NBS identified a subnetwork located in the dorsal language stream bilaterally, including supramarginal gyrus, primary sensory, motor, and auditory cortices, and insula. The connections in the subnetwork were weaker in the Broca's group than the anomic group. The properties of the subnetwork were examined through complex network measures, which indicated that regions in right inferior frontal sulcus, right paracentral lobule, and bilateral superior temporal gyrus exhibit intensive interaction. Left superior temporal gyrus, right postcentral gyrus, and left supramarginal gyrus play an important role in information flow and overall communication efficiency. Disruption of this network underlies the constellation of symptoms associated with Broca's aphasia. Whole-brain CLSM did not detect any significant connections, suggesting an advantage of NBS when thousands of connections are considered. However, CLSM identified connections that differentiated Broca's from anomic aphasia when analysis was restricted to a hypothesized network of interest. We identified novel signatures of resting-state brain network differences between groups of individuals with anomic and Broca's aphasia. We identified a subnetwork of connections that statistically differentiated the resting-state brain networks of the two groups, in comparison with standard CLSM results that yielded isolated connections. Network-level analyses are useful tools for the investigation of the neural correlates of language deficits post-stroke.

Uncovering individual variations in bystander intervention of injustice through intrinsic brain connectivity patterns

When confronted with injustice, individuals often intervene as third parties to restore justice by either punishing the perpetrator or helping the victim, even at their own expense. However, little is known about how individual differences in third-party intervention propensity are related to inter-individual variability in intrinsic brain connectivity patterns and how these associations vary between help and punishment intervention. To address these questions, we employed a novel behavioral paradigm in combination with resting-state fMRI and inter-subject representational similarity analysis (IS-RSA). Participants acted as third-party bystanders and needed to decide whether to maintain the status quo or intervene by either helping the disadvantaged recipient (Help condition) or punishing the proposer (Punish condition) at a specific cost. Our analyses focused on three brain networks proposed in the third-party punishment (TPP) model: the salience (e.g., dorsal anterior cingulate cortex, dACC), central executive (e.g., dorsolateral prefrontal cortex, dlPFC), and default mode (e.g., dorsomedial prefrontal cortex, dmPFC; temporoparietal junction, TPJ) networks. IS-RSA showed that individual differences in resting-state functional connectivity (rs-FC) patterns within these networks were associated with the general third-party intervention propensity. Moreover, rs-FC patterns of the right dlPFC and right TPJ were more strongly associated with individual differences in the helping propensity rather than the punishment propensity, whereas the opposite pattern was observed for the dmPFC. Post-hoc predictive modeling confirmed the predictive power of rs-FC in these regions for intervention propensity across individuals. Collectively, these findings shed light on the shared and distinct roles of key regions in TPP brain networks at rest in accounting for individual variations in justice-restoring intervention behaviors.

Associations Between Lifetime Musical Activity and Resting‐State Functional Connectivity in Higher‐Order Brain Networks

AbstractBackgroundEngagement in complex leisure activities, such as playing a musical instrument, may help preserve cognitive and brain health in older age (e.g. Böttcher et al., 2022). In this study, we investigated the associations between leisure‐time musical activity and resting‐state functional connectivity (RSFC) in three higher‐order networks, the Default Mode. Fronto‐Parietal and Salience Networks, in older adults.MethodIn total, 130 cognitively unimpaired older (aged 60 years and older) participants of the DZNE ‐ DELCODE (Jessen et al., 2018) were assessed. Two groups matched for their reserve proxies were identified (with musical activity during life: n = 65 and controls: n = 65) based on self‐reported musical instrument playing during life, as measured by the Lifetime of Experiences Questionnaire. The two groups were compared in global and local (seed‐to‐voxel) RSFC patterns using pre‐specified seeds of the three brain networks. A mediation analysis explored the interrelations between lifetime musical activity, RSFC, and cognitive composites (Wolfsgruber et al., 2020).ResultOlder participants with musical activity showed higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal regions, namely the bilateral temporal poles as well as the right inferior and middle temporal gyrus, compared to controls (see Figure 1). There were no group differences in global RSFC of the three networks and no mediation effects of musical activity‐related RSFC on global and domain‐specific cognition.ConclusionWe show that self‐reported lifetime musical activity relates to higher RSFC between frontal and temporal core regions of the Default Mode Network in older adults. The finding implies that playing a musical instrument during life may help preserve neural functioning in a key network that is vulnerable to aging and AD.

Sex-related differences in upper limb motor function in healthy subjects and multiple sclerosis patients: a multiparametric MRI study.

We investigated sex-related differences in upper limb motor performance tested with the 9-Hole Peg Test (9HPT) in healthy controls (HC) and multiple sclerosis (MS) patients and their MRI substrates. We enrolled 94 HC and 133 MS patients, who underwent neurological examination, 9HPT and brain 3T MRI, with sequences for regional grey matter volume (GMV), white matter (WM) fractional anisotropy (FA) and resting state (RS) functional connectivity (FC) analysis. Associations between MRI variables and 9HPT performance were analyzed with general linear models. 9HPT performance was better in HC vs MS patients, and in female vs male HC. Regional GMV analysis showed: associations between better 9HPT performance and higher GMV in motor and cognitive cortical areas in HC, with stronger positive correlations in females vs males. In MS, worse 9HPT performance correlated with lower volume in motor and cognitive areas. Sex-related differences were minimal and mostly found in cerebellar areas. WM FA analysis disclosed neither associations with 9HPT performance in HC, nor sex-related differences in MS. RS FC analysis showed: in the sensorimotor network, stronger associations of RS FC with 9HPT performance in female vs male HC and no sex-related differences in MS; in the cerebellar network, no sex-related differences in HC but stronger negative correlation in left cerebellum in male vs female MS patients. Sex influences 9HPT performance in HC, mainly through differences in volume and RS FC of motor and cognitive areas. Sex-related effects on motor performance become secondary but still present in MS.

Influence of natalizumab on resting-state connectivity in patients with multiple sclerosis.

Changes in brain connectivity occur in patients with multiple sclerosis (MS), even in patients under disease-modifying therapies. Using magnetic resonance imaging (MRI) to asses patients treated with disease-modifying therapies, such as natalizumab, can elucidate the mechanisms involved in clinical deterioration in MS. To evaluate differences in resting-state functional connectivity among MS patients treated with natalizumab, MS patients not treated with natalizumab, and controls. Single-center retrospective cross-sectional study. Twenty-three MS patients being treated with natalizumab were retrospectively compared with 23 MS patients who were naïve for natalizumab, and were using first-line medications (interferon-β and/or glatiramer acetate), and 17 gender- and age-matched control subjects. The MS patient groups were also matched for time since diagnosis and hyperintense lesion volume on FLAIR. All participants underwent brain MRI using a 3Tesla scanner. Independent component analysis and dual regression were used to identify resting-state functional connectivity using the FMRIB Software Library. In comparison to controls, the MS patients treated with natalizumab presented decreased connectivity in the left orbitofrontal cortex, in the anterior cingulate and orbitofrontal cortex network. The patients not treated with natalizumab presented increased connectivity in the secondary visual, sensorimotor, and ventral attention networks in comparison to controls.Compared to patients treated with natalizumab, the patients not using natalizumab presented increased connectivity in the left Heschl's gyrus and in the right superior frontal gyrus in the ventral attention network. Differences in brain connectivity between MS patients not treated with natalizumab, healthy controls, and patients treated with natalizumab may be secondary to suboptimal neuronal compensation due to prior less efficient treatments, or due to a compensation in response to maladaptive plasticity.

Age differences in functional brain networks associated with loneliness and empathy.

Loneliness is associated with differences in resting-state functional connectivity (RSFC) within and between large-scale networks in early- and middle-aged adult cohorts. However, age-related changes in associations between sociality and brain function into late adulthood are not well understood. Here, we examined age differences in the association between two dimensions of sociality-loneliness and empathic responding-and RSFC of the cerebral cortex. Self-report measures of loneliness and empathy were inversely related across the entire sample of younger (mean age = 22.6y, n = 128) and older (mean age = 69.0y, n = 92) adults. Using multivariate analyses of multi-echo fMRI RSFC, we identified distinct functional connectivity patterns for individual and age group differences associated with loneliness and empathic responding. Loneliness in young and empathy in both age groups was related to greater visual network integration with association networks (e.g., default, fronto-parietal control). In contrast, loneliness was positively related to within- and between-network integration of association networks for older adults. These results extend our previous findings in early- and middle-aged cohorts, demonstrating that brain systems associated with loneliness, as well as empathy, differ in older age. Further, the findings suggest that these two aspects of social experience engage different neurocognitive processes across human life-span development.

Time-of-day influences resting-state functional cortical connectivity.

Time-of-day is rarely considered during experimental protocols investigating motor behavior and neural activity. The goal of this work was to investigate differences in functional cortical connectivity at rest linked to the time of the day using functional Near-Infrared Spectroscopy (fNIRS). Since resting-state brain is shown to be a succession of cognitive, emotional, perceptual, and motor processes that can be both conscious and nonconscious, we studied self-generated thought with the goal to help in understanding brain dynamics. We used the New-York Cognition Questionnaire (NYC-Q) for retrospective introspection to explore a possible relationship between the ongoing experience and the brain at resting-state to gather information about the overall ongoing experience of subjects. We found differences in resting-state functional connectivity in the inter-hemispheric parietal cortices, which was significantly greater in the morning than in the afternoon, whilst the intra-hemispheric fronto-parietal functional connectivity was significantly greater in the afternoon than in the morning. When we administered the NYC-Q we found that the score of the question 27 ("during RS acquisition my thoughts were like a television program or film") was significantly greater in the afternoon with respect to the morning. High scores in question 27 point to a form of thought based on imagery. It is conceivable to think that the unique relationship found between NYC-Q question 27 and the fronto-parietal functional connectivity might be related to a mental imagery process during resting-state in the afternoon.

Comparison of Resting State Functional Connectivity in Persons With and Without HIV: A Cross-sectional Study.

This study examined the effects of HIV on resting state functional connectivity (RSFC) in a large cohort of people living with HIV (PWH) and healthy controls without HIV (PWoH). Within PWH analyses focused on the effects of viral suppression and cognitive impairment on RSFC. A total of 316 PWH on stable combination antiretroviral therapy and 209 demographically matched PWoH were scanned at a single institution. Effects of the virus were examined by grouping PWH by detectable (viral load > 20 copies/ml; VLD) and undetectable (VLU) viral loads and as being cognitively impaired (CI) (Global Deficit Score ≥ 0.5) or cognitively normal (CN). Regression analysis, Object Oriented Data Analysis, and spring embedded graph models were applied to RSFC measures from 298 established brain ROIs comprising 13 brain networks to examine group differences. No significant RSFC differences were observed between PWH and PWoH. Within PWH, there were no significant differences in RSFC between VLD and VLU subgroups and CI and CN subgroups. There were no significant effects of HIV on RSFC in our relatively large cohort of PWH and PWoH. Future studies could increase the sample size and combine with other imaging modalities.

Neural Circuit Markers of Familial Risk for Depression Among Healthy Youths in the Adolescent Brain Cognitive Development Study

BackgroundFamily history of depression is a robust predictor of early-onset depression, which may confer risk through alterations in neural circuits that have been implicated in reward and emotional processing. These alterations may be evident in youths who are at familial risk for depression but who do not currently have depression. However, the identification of robust and replicable findings has been hindered by few studies and small sample sizes. In the current study, we sought to identify functional connectivity (FC) patterns associated with familial risk for depression. MethodsParticipants included healthy (i.e., no lifetime psychiatric diagnoses) youths at high familial risk for depression (HR) (n = 754; at least one parent with a history of depression) and healthy youths at low familial risk for psychiatric problems (LR) (n = 1745; no parental history of psychopathology) who were 9 to 10 years of age and from the Adolescent Brain Cognitive Development (ABCD) Study sample. We conducted whole-brain seed-to-voxel analyses to examine group differences in resting-state FC with the amygdala, caudate, nucleus accumbens, and putamen. We hypothesized that HR youths would exhibit global amygdala hyperconnectivity and striatal hypoconnectivity patterns primarily driven by maternal risk. ResultsHR youths exhibited weaker caudate–angular gyrus FC than LR youths (α = 0.04, Cohen’s d = 0.17). HR youths with a history of maternal depression specifically exhibited weaker caudate–angular gyrus FC (α = 0.03, Cohen’s d = 0.19) as well as weaker caudate–dorsolateral prefrontal cortex FC (α = 0.04, Cohen’s d = 0.21) than LR youths. ConclusionsWeaker striatal connectivity may be related to heightened familial risk for depression, primarily driven by maternal history. Identifying brain-based markers of depression risk in youths can inform approaches to improving early detection, diagnosis, and treatment.

The functional connectome in obsessive-compulsive disorder: resting-state mega-analysis and machine learning classification for the ENIGMA-OCD consortium.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Disruptions of default mode network and precuneus connectivity associated with cognitive dysfunctions in tinnitus

Tinnitus is the perception of a ringing, buzzing or hissing sound “in the ear” without external stimulation. Previous research has demonstrated changes in resting-state functional connectivity in tinnitus, but findings do not overlap and are even contradictory. Furthermore, how altered functional connectivity in tinnitus is related to cognitive abilities is currently unknown. Here we investigated resting-state functional connectivity differences between 20 patients with chronic tinnitus and 20 control participants matched in age, sex and hearing loss. All participants underwent functional magnetic resonance imaging, audiometric and cognitive assessments, and filled in questionnaires targeting anxiety and depression. Significant differences in functional connectivity between tinnitus patients and control participants were not obtained. However, we did find significant associations between cognitive scores and functional coupling of the default mode network and the precuneus with the superior parietal lobule, supramarginal gyrus, and orbitofrontal cortex. Further, tinnitus distress correlated with connectivity between the precuneus and the lateral occipital complex. This is the first study providing evidence for disruptions of default mode network and precuneus coupling that are related to cognitive dysfunctions in tinnitus. The constant attempt to decrease the tinnitus sensation might occupy certain brain resources otherwise available for concurrent cognitive operations.

Glutamate levels in the ventromedial prefrontal cortex and resting-state functional connectivity within reward circuits in alcohol-dependent patients.

Great progress has been made in understanding the neural mechanisms associated with alcohol-dependent (AD) patients. However, the interactions within the reward circuits of the patients need further exploration. Glutamatergic projections from the prefrontal cortex to some brain regions are present in the reward circuit. However, little is known about the potential implications of glutamate levels in the prefrontal cortex on abnormal interactions within reward circuits in AD patients. To determine the potential roles of reward circuits in drinking, we investigated differences in resting-state functional connectivity (RSFC) and multivariate Granger causality analysis between 20 AD patients and 20 healthy controls (HC). The neuroimaging findings were then correlated with clinical variables (alcohol use disorder identification test). The ventromedial prefrontal cortex (VmPFC) is believed to play a critical role in addiction disorders, and glutamatergic projections from the prefrontal cortex to several regions of the brain are present in reward circuits. Proton magnetic resonance spectroscopy was also performed to assess the difference in glutamate levels in VmPFC between AD patients and HC. The results showed that the strength of functional connectivity in the reward circuit was generally attenuated in AD patients, and the reciprocal enhancement of activity between the right insula, left thalamus and VmPFC was found to be significantly greater in AD patients. It is worth noting that although glutamate levels in the VmPFC did not show significant differences between the two groups, the level of glutamate in the VmPFC was significantly correlated with RSFC. We hope that the current findings will help us to develop new intervention models based on the important role of the VmPFC in AD.

Neuroplasticity of pain processing and motor control in CAI patients: A UK Biobank study with clinical validation.

Pain plays an important role in chronic ankle instability (CAI), and prolonged pain may be associated with ankle dysfunction and abnormal neuroplasticity. To investigate the differences in resting-state functional connectivity among the pain-related brain regions and the ankle motor-related brain regions between healthy controls and patients with CAI, and explore the relationship between patients' motor function and pain. A cross-database, cross-sectional study. This study included a UK Biobank dataset of 28 patients with ankle pain and 109 healthy controls and a validation dataset of 15 patients with CAI and 15 healthy controls. All participants underwent resting-state functional magnetic resonance imaging scanning, and the functional connectivity (FC) among the pain-related brain regions and the ankle motor-related brain regions were calculated and compared between groups. The correlations between the potentially different functional connectivity and the clinical questionnaires were also explored in patients with CAI. The functional connection between the cingulate motor area and insula significantly differed between groups in both the UK Biobank (p = 0.005) and clinical validation dataset (p = 0.049), which was also significantly correlated with Tegner scores (r = 0.532, p = 0.041) in patients with CAI. A reduced functional connection between the cingulate motor area and the insula was present in patients with CAI, which was also directly correlated with reduction in the level of patient physical activity.