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Background: Charles Bonnet syndrome (CBS) is a condition in which people with vision loss experience complex visual hallucinations. These complex visual hallucinations may be caused by increased excitability in the visual cortex that are present in some people with vision loss but not others. Objectives: We aimed to evaluate the association between γ-aminobutyric acid (GABA) in the visual cortex and CBS. We also tested the relationship among visually evoked responses, functional connectivity, and CBS. Design: This is a prospective, case-controlled, cross-sectional observational study. Methods: We applied 3-Tesla magnetic resonance spectroscopy, as well as task-based and resting state (RS) connectivity functional magnetic resonance imaging in six participants with CBS and six controls without CBS. GABA+ was measured in the early visual cortex (EVC) and in the lateral occipital cortex (LOC). Participants also completed visual acuity and cognitive tests, and the North-East Visual Hallucinations Interview. Results: The two groups were well-matched for age, gender, visual acuity and cognitive scores. There was no difference in GABA+ levels between groups in the visual cortex. Most participants showed the expected blood oxygenation level dependent (BOLD) activation to images of objects and the phase-scrambled control. Using a fixed effects analysis, we found that BOLD activation was greater in participants with CBS compared to controls. Analysis of RS connectivity with LOC and EVC showed little difference between groups. A fixed effects analysis showed a correlation between the extent of functional connectivity with LOC and hallucination strength. Conclusion: Overall, our results provide no strong evidence for an association between GABAergic inhibition in the visual cortex and CBS. We only found subtle differences in visual function and connectivity between groups. These findings suggest that the neurochemistry and visual connectivity for people with Charles Bonnet hallucinations are comparable to a sight loss population. Differences between groups may emerge when investigating subtle and transient changes that occur at the time of visual hallucinations. Plain language summary: Brain imaging in Charles Bonnet syndrome In Charles Bonnet Syndrome (CBS), people with sight loss start to see hallucinations that they know are not real but can be disturbing. In this study we used MRI scanning to measure how the chemistry in the visual brain differs in people with CBS and those who have sight loss but no hallucinations. Surprisingly we did not find any differences in chemistry between these groups, suggesting that their brains do not differ greatly. Any differences in how their visual brain works may be too small to measure, or only present when people hallucinate. [ABSTRACT FROM AUTHOR]

Introduction: Suicide is a current leading cause of death in adolescents and young adults. The neurobiological underpinnings of suicide risk in youth, however, remain unclear and a brain-based model is lacking. In adult samples, current models highlight deficient serotonin release as a potential suicide biomarker, and in particular, involvement of serotonergic dysfunction in relation to the putamen and suicidal behavior. Less is known about associations among striatal regions and relative suicidal risk across development. The current study examined putamen connectivity in depressed adolescents with (AT) and without history of a suicide attempt (NAT), specifically using resting-state functional magnetic resonance imaging (fMRI) to evaluate patterns in resting-state functional connectivity (RSFC). We hypothesized the AT group would exhibit lower striatal RSFC compared to the NAT group, and lower striatal RSFC would associate with greater suicidal ideation severity and/or lethality of attempt. Methods: We examined whole-brain RSFC of six putamen regions in 17 adolescents with depression and NAT (MAge [SD] = 16.4[0.3], 41% male) and 13 with AT (MAge [SD] = 16.2[0.3], 31% male). Results: Only the dorsal rostral striatum showed a statistically significant bilateral between-group difference in RSFC with the superior frontal gyrus and supplementary motor area, with higher RSFC in the group without a suicide attempt compared to those with attempt history (voxel-wise p<.001, clusterwise p<.01). No significant associations were found between any putamen RSFC patterns and suicidal ideation severity or lethality of attempts among those who had attempted. Discussion: The results align with recent adult literature and have interesting theoretical and clinical implications. A possible interpretation of the results is a mismatch of the serotonin transport to putamen and to the supplementary motor area and the resulting reduced functional connectivity between the two areas in adolescents with attempt history. The obtained results can be used to enhance the diathesis-stress model and the Emotional paiN and social Disconnect (END) model of adolescent suicidality by adding the putamen. We also speculate that connectivity between putamen and the supplementary motor area may in the future be used as a valuable biomarker of treatment efficacy and possibly prediction of treatment outcome. [ABSTRACT FROM AUTHOR]

IntroductionSuicide is a current leading cause of death in adolescents and young adults. The neurobiological underpinnings of suicide risk in youth, however, remain unclear and a brain-based model is lacking. In adult samples, current models highlight deficient serotonin release as a potential suicide biomarker, and in particular, involvement of serotonergic dysfunction in relation to the putamen and suicidal behavior. Less is known about associations among striatal regions and relative suicidal risk across development. The current study examined putamen connectivity in depressed adolescents with (AT) and without history of a suicide attempt (NAT), specifically using resting-state functional magnetic resonance imaging (fMRI) to evaluate patterns in resting-state functional connectivity (RSFC). We hypothesized the AT group would exhibit lower striatal RSFC compared to the NAT group, and lower striatal RSFC would associate with greater suicidal ideation severity and/or lethality of attempt.MethodsWe examined whole-brain RSFC of six putamen regions in 17 adolescents with depression and NAT (MAge [SD] = 16.4[0.3], 41% male) and 13 with AT (MAge [SD] = 16.2[0.3], 31% male).ResultsOnly the dorsal rostral striatum showed a statistically significant bilateral between-group difference in RSFC with the superior frontal gyrus and supplementary motor area, with higher RSFC in the group without a suicide attempt compared to those with attempt history (voxel-wise p

Relatively little is known about associations between peripheral inflammation and neural function in humans. Neuroimaging studies in adults have suggested that elevated peripheral inflammatory markers are associated with altered resting state functional connectivity (rsFC) in several brain networks associated with mood and cognition. Few studies have examined these associations in adolescents, yet scarce data from adolescents point to different networks than adult studies. The current study examined the associations between peripheral inflammation and rsFC in a community sample of adolescents (n = 70; age, 12-15 years; 32 female, 36 male, 2 nonbinary). After blood sampling, an fMRI scan was performed to assess rsFC. Assay for serum inflammatory markers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP), was performed. Results indicated that higher TNF-α was associated with altered rsFC between the right amygdala and left striatum and between the right inferior frontal gyrus and left parietal cortex (p

Objective: Predicting memory morbidity after temporal lobectomy in patients with temporal lobe epilepsy (TLE) relies on indices of preoperative temporal lobe structural and functional integrity. However, epilepsy is increasingly considered a network disorder, and memory a network phenomenon. We assessed the utility of functional network measures to predict postoperative memory changes. Methods: Seventy‐two adults with TLE (37 left/35 right) underwent preoperative resting‐state functional magnetic resonance imaging and pre‐ and postoperative neuropsychological assessment. We compared functional connectivity throughout the memory network of each patient to a healthy control template (n = 19) to identify differences in global organization. A second metric indicated the degree of integration of the to‐be‐resected temporal lobe with the rest of the memory network. We included these measures in a linear regression model alongside standard clinical variables as predictors of memory change after surgery. Results: Left TLE patients with more atypical memory networks, and with greater functional integration of the to‐be‐resected region with the rest of the memory network preoperatively, experienced the greatest decline in verbal memory after surgery. Together, these two measures explained 44% of variance in verbal memory change, outperforming standard clinical and demographic variables. None of the variables examined was associated with visuospatial memory change in patients with right TLE. Significance: Resting‐state connectivity provides valuable information concerning both the integrity of to‐be‐resected tissue and functional reserve across memory‐relevant regions outside of the to‐be‐resected tissue. Intrinsic functional connectivity has the potential to be useful for clinical decision‐making regarding memory outcomes in left TLE, and more work is needed to identify the factors responsible for differences seen in right TLE. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is a prevalent mental health condition affecting millions worldwide, leading to disability and reduced quality of life. MDD poses a global health priority due to its early onset and association with other disabling conditions. Available treatments for MDD exhibit varying effectiveness, and a substantial portion of individuals remain resistant to treatment. Repetitive transcranial magnetic stimulation (rTMS), applied to the left and/or right dorsolateral prefrontal cortex (DLPFC), is an alternative treatment strategy for those experiencing treatment-resistant MDD. The objective of this study is to investigate whether this newer form of rTMS, namely theta burst stimulation (TBS), when performed unilaterally or bilaterally, is efficacious in treatment-resistant MDD. Methods: In this naturalistic, randomized double-blinded non-inferiority trial, participants with a major depressive episode will be randomized to receive either unilateral (i.e., continuous TBS [cTBS] to the right and sham TBS to the left DLPFC) or bilateral sequential TBS (i.e., cTBS to the right and intermittent TBS [iTBS] to the left DLPFC) delivered 5 days a week for 4–6 weeks. Responders will move onto a 6-month flexible maintenance phase where TBS treatment will be delivered at a decreasing frequency depending on degree of symptom mitigation. Several clinical assessments and neuroimaging and neurophysiological biomarkers will be collected to investigate treatment response and potential associated biomarkers. A non-inferiority analysis will investigate whether bilateral sequential TBS is non-inferior to unilateral TBS and regression analyses will investigate biomarkers of treatment response. We expect to recruit a maximal of 256 participants. This trial is approved by the Research Ethics Board of The Royal's Institute of Mental Health Research (REB# 2,019,071) and will follow the Declaration of Helsinki. Findings will be published in peer-reviewed journals. Discussion: Comprehensive assessment of symptoms and neurophysiological biomarkers will contribute to understanding the differential efficacy of the tested treatment protocols, identifying biomarkers for treatment response, and shedding light into underlying mechanisms of TBS. Our findings will inform future clinical trials and aid in personalizing treatment selection and scheduling for individuals with MDD. Trial registration: The trial is registered on https://clinicaltrials.gov/ct2/home (#NCT04142996). [ABSTRACT FROM AUTHOR]

Background: Resting state connectivity studies link ketamine's antidepressant effects with normalisation of the brain connectivity changes that are observed in depression. These changes, however, usually co-occur with improvement in depressive symptoms, making it difficult to attribute these changes to ketamine's effects per se. Aims: Our aim is to examine the effects of ketamine in brain connectivity, 2 h after its administration in a cohort of volunteers with remitted depression. Any significant changes observed in this study could provide insight of ketamine's antidepressant mechanism as they are not accompanied by symptom changes. Methods: In total, 35 participants with remitted depression (21 females, mean age = 28.5 years) participated in a double-blind, placebo-controlled study of ketamine (0.5 mg/kg) or saline. Resting state scans were acquired approximately 2 h after the ketamine infusion. Brain connectivity was examined using a seed-based approach (ventral striatum, amygdala, hippocampus, posterior cingulate cortex and subgenual anterior cingulate cortex (sgACC)) and a brain network analysis (independent component analysis). Results: Decreased connectivity between the sgACC and the amygdala was observed approximately 2 h after the ketamine infusion, compared to placebo (p FWE < 0.05). The executive network presented with altered connectivity with different cortical and subcortical regions. Within the network, the left hippocampus and right amygdala had decreased connectivity (p FWE < 0.05). Conclusions: Our findings support a model whereby ketamine would change the connectivity of brain areas and networks that are important for cognitive processing and emotional regulation. These changes could also be an indirect indicator of the plasticity changes induced by the drug. [ABSTRACT FROM AUTHOR]

Traumatic brain injury damages white matter pathways that connect brain regions, disrupting transmission of electrochemical signals and causing cognitive and emotional dysfunction. Connectome-level mechanisms for how the brain compensates for injury have not been fully characterized. Here, we collected serial MRI-based structural and functional connectome metrics and neuropsychological scores in 26 mild traumatic brain injury subjects (29.4 ± 8.0 years, 20 males) at 1 and 6 months postinjury. We quantified the relationship between functional and structural connectomes using network diffusion (ND) model propagation time, a measure that can be interpreted as how much of the structural connectome is being utilized for the spread of functional activation, as captured via the functional connectome. Overall cognition showed significant improvement from 1 to 6 months (t25 = -2.15, p = .04). None of the structural or functional global connectome metrics was significantly different between 1 and 6 months, or when compared to 34 age- and gender-matched controls (28.6 ± 8.8 years, 25 males). We predicted longitudinal changes in overall cognition from changes in global connectome measures using a partial least squares regression model (cross-validated R2 = .27). We observe that increased ND model propagation time, increased structural connectome segregation, and increased functional connectome integration were related to better cognitive recovery. We interpret these findings as suggesting two connectome-based postinjury recovery mechanisms: one of neuroplasticity that increases functional connectome integration and one of remote white matter degeneration that increases structural connectome segregation. We hypothesize that our inherently multimodal measure of ND model propagation time captures the interplay between these two mechanisms.

IntroductionA short-term immobilization of one hand affects musculoskeletal functions, and the associated brain network adapts to the alterations happening to the body due to injuries. It was hypothesized that the injury-associated temporary disuse of the upper limb would alter the functional interactions of the motor cortical processes and will produce long-term changes throughout the immobilization and post-immobilization period.MethodsThe case participant (male, 12 years old, right arm immobilized for clavicle fracture) was scanned using optical imaging technology of fNIRS over immobilization and post-immobilization. Pre-task data was collected for 3 min for RSFC analysis, processed, and analyzed using the Brain AnalyzIR toolbox. Connectivity was measured using Pearson correlation coefficients (R) from NIRS Toolbox's connectivity module.ResultsThe non-affected hand task presented an increased ipsilateral response during the immobilization period, which then decreased over the follow-up visits. The right-hand task showed a bilateral activation pattern following immobilization, but the contralateral activation pattern was restored during the 1-year follow-up visit. Significant differences in the average connection strength over the study period were observed. The average Connection strength decreased from the third week of immobilization and continued to be lower than the baseline value. Global network efficiency decreased in weeks two and three, while the network settled into a higher efficient state during the follow-up periods after post-immobilization.DiscussionShort-term immobilization of the upper limb is shown to have cortical changes in terms of activations of brain regions as well as connectivity. The short-term dis-use of the upper limb has shifted the unilateral activation pattern to the bilateral coactivation of the motor cortex from both hemispheres. Resting-state data reveals a disruption in the motor cortical network during the immobilization phase, and the network is reorganized into an efficient network over 1 year after the injury. Understanding such cortical reorganization could be informative for studying the recovery from neurological disorders affecting motor control in the future.

Summary: Background: Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2–4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms. Methods: In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve). MRI Imaging was carried out between the 15th July and 17th November 2020 at the Queen Square House Clinical Scanning Facility, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole brain grey matter (GM) cerebral blood flow (CBF) and GM density. Findings: Individuals with anosmia showed increased FC between the left orbitofrontal cortex (OFC), visual association cortex and cerebellum and FC reductions between the right OFC and dorsal anterior cingulate cortex compared to those with no prior COVID-19 infection (p

Patients with Alzheimer's disease vary in their ability to sustain cognitive abilities in the presence of brain pathology. A major open question is which brain mechanisms may support higher reserve capacity, i.e. relatively high cognitive performance at a given level of Alzheimer's pathology. Higher functional MRI-assessed functional connectivity of a hub in the left frontal cortex is a core candidate brain mechanism underlying reserve as it is associated with education (i.e. a protective factor often associated with higher reserve) and attenuated cognitive impairment in prodromal Alzheimer's disease. However, no study has yet assessed whether such hub connectivity of the left frontal cortex supports reserve throughout the evolution of pathological brain changes in Alzheimer's disease, including the presymptomatic stage when cognitive decline is subtle. To address this research gap, we obtained cross-sectional resting state functional MRI in 74 participants with autosomal dominant Alzheimer's disease, 55 controls from the Dominantly Inherited Alzheimer's Network and 75 amyloid-positive elderly participants, as well as 41 amyloid-negative cognitively normal elderly subjects from the German Center of Neurodegenerative Diseases multicentre study on biomarkers in sporadic Alzheimer's disease. For each participant, global left frontal cortex connectivity was computed as the average resting state functional connectivity between the left frontal cortex (seed) and each voxel in the grey matter. As a marker of disease stage, we applied estimated years from symptom onset in autosomal dominantly inherited Alzheimer's disease and cerebrospinal fluid tau levels in sporadic Alzheimer's disease cases. In both autosomal dominant and sporadic Alzheimer's disease patients, higher levels of left frontal cortex connectivity were correlated with greater education. For autosomal dominant Alzheimer's disease, a significant left frontal cortex connectivity × estimated years of onset interaction was found, indicating slower decline of memory and global cognition at higher levels of connectivity. Similarly, in sporadic amyloid-positive elderly subjects, the effect of tau on cognition was attenuated at higher levels of left frontal cortex connectivity. Polynomial regression analysis showed that the trajectory of cognitive decline was shifted towards a later stage of Alzheimer's disease in patients with higher levels of left frontal cortex connectivity. Together, our findings suggest that higher resilience against the development of cognitive impairment throughout the early stages of Alzheimer's disease is at least partially attributable to higher left frontal cortex-hub connectivity.

The transition from adolescent to adult cognition and emotional control requires neurodevelopmental maturation likely involving intrinsic functional networks (IFNs). Normal neurodevelopment may be vulnerable to disruption from environmental insult such as alcohol consumption commonly initiated during adolescence. To test potential disruption to IFN maturation, we used resting-state functional magnetic resonance imaging (rs-fMRI) in 581 no-to-low alcohol-consuming and 117 moderate-to-high-drinking youth. Functional seed-to-voxel connectivity analysis assessed age, sex, and moderate alcohol drinking on default-mode, executive-control, salience, reward, and emotion networks and tested cognitive and motor coordination correlates of network connectivity. Among no-to-low alcohol-consuming adolescents, executive-control frontolimbicstriatal connectivity was stronger in older than younger adolescents, particularly boys, and predicted better ability in balance, memory, and impulse control. Connectivity patterns in moderate-to-high-drinking youth were tested mainly in late adolescence when drinking was initiated. Implicated was the emotion network with attenuated connectivity to default-mode network regions. Our cross-sectional rs-fMRI findings from this large cohort of adolescents show sexual dimorphism in connectivity and suggest neurodevelopmental rewiring toward stronger and spatially more distributed executive-control networking in older than younger adolescents. Functional network rewiring in moderate-to-high-drinking adolescents may impede maturation of affective and self-reflection systems and obscure maturation of complex social and emotional behaviors.

Experiencing stress before an event can influence how that event is later remembered. In the current study, we examine how individual differences in one's physiological response to a stressor are related to changes to underlying brain states and memory performance. Specifically, we examined how changes in intrinsic amygdala connectivity relate to positive and negative memory performance as a function of stress response, defined as a change in cortisol. Twenty‐five participants underwent a social stressor before an incidental emotional memory encoding task. Cortisol samples were obtained before and after the stressor to measure individual differences in stress response. Three resting state scans (pre‐stressor, post‐stressor/pre‐encoding and post‐encoding) were conducted to evaluate pre‐ to post‐stressor and pre‐ to post‐encoding changes to intrinsic amygdala connectivity. Analyses examined relations between greater cortisol changes and connectivity changes. Greater cortisol increases were associated with a greater decrease in prefrontal‐amygdala connectivity following the stressor and a reversal in the relation between prefrontal‐amygdala connectivity and negative vs. positive memory performance. Greater cortisol increases were also associated with a greater increase in amygdala connectivity with a number of posterior sensory regions following encoding. Consistent with prior findings in non‐stressed individuals, pre‐ to post‐encoding increases in amygdala‐posterior connectivity were associated with greater negative relative to positive memory performance, although this was specific to lateral rather than medial posterior regions and to participants with the greatest cortisol changes. These findings suggest that stress response is associated with changes in intrinsic connectivity that have downstream effects on the valence of remembered emotional content. [ABSTRACT FROM AUTHOR]

ObjectivePeripheral inflammation has been associated with adverse effects on cognition and brain structure in late life, a process called 'inflammaging.' Identifying biomarkers of preclinical cognitive decline is critical in the development of preventative therapies, and peripheral inflammation may be able to serve as an indicator of cognitive decline. However, little is known regarding the relationship between peripheral inflammation and brain structure and function among older adults.MethodsTwenty-four older adults (mean age = 78) underwent a functional magnetic resonance imaging (fMRI) resting state functional connectivity scan, and a subset (n = 14) completed the n-Back working memory task in the scanner. All participants completed a blood draw, and inflammation was measured with interleukin 6 (IL-6) and C-Reactive Protein (CRP).ResultsSurprisingly, age was unrelated to measures of inflammation (IL-6, CRP) or brain function (default mode network (DMN) connectivity; working memory performance; blood oxygenation level dependent (BOLD) activation with higher working memory load). However, lower functional connectivity between the left parietal seed and all other DMN regions was associated with higher levels of IL-6 and CRP. Additionally, greater plasma concentration of IL-6 was associated with lower BOLD activation in the left middle frontal gyrus in response to increased working memory load.ConclusionsThese preliminary findings support the importance of IL-6 and CRP in brain function among older adults. Frontal and parietal regions may be particularly sensitive to the effects of inflammation. Additionally, these findings provide preliminary evidence of inflammatory contributions to level of neural activity, even after accounting for vascular risk factors.

Background: The neural mechanisms associated with anhedonia treatment response are poorly understood. Additionally, no study has investigated changes in resting-state functional connectivity (rsFC) accompanying psychosocial treatment for anhedonia.Methods: We evaluated a novel psychotherapy, Behavioral Activation Therapy for Anhedonia (BATA, n = 38) relative to Mindfulness-Based Cognitive Therapy (MBCT, n = 35) in a medication-free, transdiagnostic, anhedonic sample in a parallel randomized controlled trial. Participants completed up to 15 sessions of therapy and up to four 7T MRI scans before, during, and after treatment (n = 185 scans). Growth curve models estimated change over time in anhedonia and in rsFC using average region-of-interest (ROI)-to-ROI connectivity within the default mode network (DMN), frontoparietal network (FPN), salience network, and reward network. Changes in rsFC from pre- to post-treatment were further evaluated using whole-network seed-to-voxel and ROI-to-ROI edgewise analyses.Results: Growth curve models showed significant reductions in anhedonia symptoms and in average rsFC within the DMN and FPN over time, across BATA and MBCT. There were no differences in anhedonia reductions between treatments. Within-person, changes in average rsFC were unrelated to changes in anhedonia. Between-person, higher than average FPN rsFC was related to less anhedonia across timepoints. Seed-to-voxel and edgewise rsFC analyses corroborated reductions within the DMN and between the DMN and FPN over time, across the sample.Conclusions: Reductions in rsFC within the DMN, FPN, and between these networks co-occurred with anhedonia improvement across two psychosocial treatments for anhedonia. Future anhedonia clinical trials with a waitlist control group should disambiguate treatment versus time-related effects on rsFC. [ABSTRACT FROM AUTHOR]

• Resting state functional brain connectivity was measured before and after motor practice. • Expectancy-enhancing feedback during practice is thought to engage dopaminergic pathways. • Positive feedback during motor practice increased dopaminergic neural pathway connectivity. • The positive social comparative feedback was not sufficient to drive the expected behavioral effects. Positive social comparative feedback is hypothesized to generate a dopamine response in the brain, similar to reward, by enhancing expectancies to support motor skill learning. However, no studies have utilized neuroimaging to examine this hypothesized dopaminergic mechanism. Therefore, the aim of this preliminary study was to investigate the effect of positive social comparative feedback on dopaminergic neural pathways measured by resting state connectivity. Thirty individuals practiced an implicit, motor sequence learning task and were assigned to groups that differed in feedback type. One group received feedback about their actual response time to complete the task (RT ONLY), while the other group received feedback about their response time with positive social comparison (RT + POS). Magnetic resonance imaging was acquired at the beginning and end of repetitive motor practice with feedback to measure practice-dependent changes in resting state brain connectivity. While both groups showed improvements in task performance and increases in performance expectancies, ventral tegmental area and the left nucleus accumbens (mesolimbic dopamine pathway) resting state connectivity increased in the RT + POS group but not in the RT ONLY group. Instead, the RT ONLY group showed increased connectivity between ventral tegmental area and primary motor cortex. Positive social comparative feedback during practice of a motor sequence task may induce a dopaminergic response in the brain along the mesolimbic pathway. However, given that absence of effects on expectancies and motor learning, more robust and individualized approaches may be needed to provide beneficial psychological and behavioral effects. [ABSTRACT FROM AUTHOR]

Distinctive cortico-striatal circuits that serve motor and cognitive functions have been recently mapped based on resting state connectivity. It has been reported that age differences in cortico-striatal connectivity relate to cognitive declines in aging. Moreover, children in their early teens (i.e., youth) already show mature motor network patterns while their cognitive networks are still developing. In the current study, we examined age differences in the frontal-striatal "cognitive" and "motor" circuits in children and adolescence, young adults (YAs), and older adults (OAs). We predicted that the strength of the "cognitive" frontal-striatal circuits would follow an inverted "U" pattern across age; children and OAs would have weaker connectivity than YAs. However, we predicted that the "motor" circuits would show less variation in connectivity strength across the lifespan. We found that most areas in both the "cognitive" and "motor" circuits showed higher connectivity in YAs than children and OAs, suggesting general inverted "U"-shaped changes across the lifespan for both the cognitive and motor frontal-striatal networks.

• We examined associations between inflammation and brain connectivity in adolescents. • TNF-α was associated with increased amygdala-striatum connectivity. • TNF-α was associated with decreased prefrontal-parietal connectivity. • Results indicate mechanisms through which inflammation may influence mental health. Relatively little is known about associations between peripheral inflammation and neural function in humans. Neuroimaging studies in adults have suggested that elevated peripheral inflammatory markers are associated with altered resting state functional connectivity (rsFC) in several brain networks associated with mood and cognition. Few studies have examined these associations in adolescents, yet scarce data from adolescents point to different networks than adult studies. The current study examined the associations between peripheral inflammation and rsFC in a community sample of adolescents (n = 70; age, 12–15 years; 32 female, 36 male, 2 nonbinary). After blood sampling, an fMRI scan was performed to assess rsFC. Assay for serum inflammatory markers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP), was performed. Results indicated that higher TNF-α was associated with altered rsFC between the right amygdala and left striatum and between the right inferior frontal gyrus and left parietal cortex (p < 0.05 whole-brain corrected). Associations with IL-6 and CRP were not significant. In contrast with findings in adults, inflammation may have unique links with the connectivity of the developing adolescent brain. Results have implications for understanding how peripheral inflammation may influence connectivity during adolescence, when neural networks are undergoing major developmental changes. [ABSTRACT FROM AUTHOR]

Cerebellar contributions to behavior in advanced age are of interest and importance, given its role in motor and cognitive performance. There are differences and declines in cerebellar structure in advanced age and cerebellar resting state connectivity is lower. However, the work on this area to date has focused on the cerebellar cortex. The deep cerebellar nuclei provide the primary cerebellar inputs and outputs to the cortex, as well as the spinal and vestibular systems. Dentate networks can be dissociated such that the dorsal region is associated with the motor cortex, whereas the ventral aspect is associated with the prefrontal cortex. However, whether dentato-thalamo-cortical networks differ across adulthood remains unknown. Here, using a large adult sample (n = 590) from the Cambridge Center for Ageing and Neuroscience, we investigated dentate connectivity across adulthood. We replicated past work showing dissociable resting state networks in the dorsal and ventral aspects of the dentate. In both seeds, we demonstrated that connectivity is lower with advanced age, indicating that connectivity differences extend beyond the cerebellar cortex. Finally, we demonstrated sex differences in dentate connectivity. This expands our understanding of cerebellar circuitry in advanced age and underscores the potential importance of this structure in age-related performance differences. [ABSTRACT FROM AUTHOR]

Cocaine-dependent (CD) individuals demonstrate significant anxiety and dysphoria during withdrawal, a negative emotional state that may perpetuate drug seeking and consumption. An extensive body of work has focused on characterizing reward circuit dysfunction, but relatively little is known about the pain circuit during cocaine withdrawal. In an earlier study, we highlighted how cue-elicited functional connectivity between the periaqueductal gray (PAG), a subcortical hub of the pain circuit, and ventromedial prefrontal cortex supports tonic craving in recently abstinent CD. The functional organization of the brain can be characterized by intrinsic connectivities, and it is highly likely that the resting state functional connectivity (rsFC) of the PAG may also be altered in association with cocaine use variables. Here, we examined this issue in 52 CD and 52 healthy control (HC) participants. Imaging data were processed with published routines, and the findings were evaluated with a corrected threshold. In a covariance analysis, CD as compared with HC showed higher PAG rsFC with the hypothalamus, dorsomedial prefrontal, and inferior parietal cortices. Further, these connectivities were correlated negatively with tonic cocaine craving and recent cocaine use, respectively. Higher hypothalamic and frontoparietal rsFC with the PAG may reflect a compensatory process to regulate craving and compulsive drug use. The findings provide additional evidence in humans implicating the PAG circuit and may help research of the role of negative reinforcement in sustaining habitual drug use in cocaine addiction. [ABSTRACT FROM AUTHOR]

Misophonia is a common disorder characterized by the experience of strong negative emotions of anger and anxiety in response to certain everyday sounds, such as those generated by other people eating, drinking, and breathing. The commonplace nature of these “trigger” sounds makes misophonia a devastating disorder for sufferers and their families. How such innocuous sounds trigger this response is unknown. Since most trigger sounds are generated by orofacial movements (e.g., chewing) in others, we hypothesized that the mirror neuron system related to orofacial movements could underlie misophonia. We analyzed resting state fMRI (rs-fMRI) connectivity (N = 33, 16 females) and sound-evoked fMRI responses (N = 42, 29 females) in misophonia sufferers and controls. We demonstrate that, compared with controls, the misophonia group show no difference in auditory cortex responses to trigger sounds, but do show: (1) stronger rs-fMRI connectivity between both auditory and visual cortex and the ventral premotor cortex responsible for orofacial movements; (2) stronger functional connectivity between the auditory cortex and orofacial motor area during sound perception in general; and (3) stronger activation of the orofacial motor area, specifically, in response to trigger sounds. Our results support a model of misophonia based on “hyper-mirroring” of the orofacial actions of others with sounds being the “medium” via which action of others is excessively mirrored. Misophonia is therefore not an abreaction to sounds, per se, but a manifestation of activity in parts of the motor system involved in producing those sounds. This new framework to understand misophonia can explain behavioral and emotional responses and has important consequences for devising effective therapies. [ABSTRACT FROM AUTHOR]

Chronic low back pain (LBP) is a very common health problem worldwide and a major cause of disability. Yet, the lack of quantifiable metrics on which to base clinical decisions leads to imprecise treatments, unnecessary surgery and reduced patient outcomes. Although, the focus of LBP has largely focused on the spine, the literature demonstrates a robust reorganization of the human brain in the setting of LBP. Brain neuroimaging holds promise for the discovery of biomarkers that will improve the treatment of chronic LBP. In this study, we report on morphological changes in cerebral cortical thickness (CT) and resting-state functional connectivity (rsFC) measures as potential brain biomarkers for LBP. Structural MRI scans, resting state functional MRI scans and self-reported clinical scores were collected from 24 LBP patients and 27 age-matched healthy controls (HC). The results suggest widespread differences in CT in LBP patients relative to HC. These differences in CT are correlated with self-reported clinical summary scores, the Physical Component Summary and Mental Component Summary scores. The primary visual, secondary visual and default mode networks showed significant age-corrected increases in connectivity with multiple networks in LBP patients. Cortical regions classified as hubs based on their eigenvector centrality (EC) showed differences in their topology within motor and visual processing regions. Finally, a support vector machine trained using CT to classify LBP subjects from HC achieved an average classification accuracy of 74.51%, AUC = 0.787 (95% CI: 0.66–0.91). The findings from this study suggest widespread changes in CT and rsFC in patients with LBP while a machine learning algorithm trained using CT can predict patient group. Taken together, these findings suggest that CT and rsFC may act as potential biomarkers for LBP to guide therapy.

Abstract Background Posttraumatic stress disorder (PTSD) is associated with abnormal hippocampal activity; however, the functional connectivity (FC) of the hippocampus with other brain regions in PTSD and its relations with symptoms warrants further attention. We investigated subregional hippocampal FC in PTSD during a resting state compared with a trauma-exposed control (TEC) group. Based on extant research, we targeted the FCs of the anterior and posterior hippocampal subregions with the amygdala, medial prefrontal cortex (mPFC), and the posterior cingulate (PCC). Methods Resting-state functional magnetic resonance images were acquired from 11 individuals with PTSD and 13 trauma-exposed controls. Anterior and posterior hippocampal FC was compared between groups. Within the PTSD and TEC groups, subregional hippocampal FC was correlated with scores on the Clinician-Administered PTSD Scale (CAPS) at time of scan and 4 months post-scan. Results Those with PTSD had significantly greater FC compared with the TEC group between the left posterior hippocampus and the bilateral PCC (g’s > .96). Direct contrasts of the Fisher z-transformed coefficients indicated that the correlations between CAPS scores 4 months post scan and the FC between the left hippocampal head and the right PCC (z = − 2.07, p = .039) as well as the FC between the right hippocampal tail and the right mPFC (z = − 2.19, p = .029) were significantly greater in the PTSD group compared to the TEC group. Conclusions These results support between-group differences in posterior hippocampal FC and different relations with PTSD future symptoms, underscoring associations with the anterior and posterior hippocampus. These findings enrich our understanding of PTSD pathophysiology and provide support for future investigations of imaging biomarkers predictive of disease progression.

In Alzheimer's disease, the tauopathy is known as a major mechanism responsible for the development of cognitive deficits. Early biomarkers of such affectations for diagnosis/stratification are crucial in Alzheimer's disease research, and brain connectome studies increasingly show their potential establishing pathology fingerprints at the network level. In this context, we conducted an in vivo multimodal MRI study on young Thy-Tau22 transgenic mice expressing tauopathy, performing resting state functional MRI and structural brain imaging to identify early connectome signatures of the pathology, relating with histological and behavioural investigations. In the prodromal phase of tauopathy, before the emergence of cognitive impairments, Thy-Tau22 mice displayed selective modifications of brain functional connectivity involving three main centres: hippocampus (HIP), amygdala (AMG) and the isocortical areas, notably the somatosensory (SS) cortex. Each of these regions showed differential histopathological profiles. Disrupted ventral HIP-AMG functional pathway and altered dynamic functional connectivity were consistent with high pathological tau deposition and astrogliosis in both hippocampus and amygdala, and significant microglial reactivity in amygdalar nuclei. These patterns were concurrent with widespread functional hyperconnectivity of memory-related circuits of dorsal hippocampus-encompassing dorsal HIP-SS communication-in the absence of significant cortical histopathological markers. These findings suggest the coexistence of two intermingled mechanisms of response at the functional connectome level in the early phases of pathology: a maladaptive and a likely compensatory response. Captured in the connectivity patterns, such first responses to pathology could further be used in translational investigations as a lead towards an early biomarker of tauopathy as well as new targets for future treatments. [ABSTRACT FROM AUTHOR]

Human and animal studies have shown that heavy cannabis (CB) use interacts with glutamatergic signaling. Additionally, recent studies have suggested that glutamate (Glu) may drive resting state functional connectivity (RSfc). The aims of the current preliminary study were to: 1) determine whether dorsal anterior cingulate cortex (dACC) Glu is related to RSfc between the dACC and two nodes of the reward network, the nucleus accumbens (NAc) and hippocampus (Hp); and 2) determine whether CB use interacts with the relationship between dACC Glu and RSfc. A group of 23 chronic CB users and 23 healthy controls participated in this multimodal MRI study. Glu levels were assessed in the dACC using magnetic resonance spectroscopy (MRS). Linear regression models were used to determine whether dACC Glu and CB use predicts RSfc between the dACC and the NAc and Hp. While the effect size is small, the results showed that the connectivity between the dACC and right NAc was predicted by the interaction between dACC Glu levels and monthly CB use. Additionally, while there is some suggestion that dACC Glu is correlated with dACC-hippocampal connectivity, unlike for dACC/NAc connectivity the relationship between them does not appear to be affected by CB use. These preliminary findings are significant in that they demonstrate the need for future studies with larger sample sizes to better characterize the relationship between resting state connectivity and neurochemistry as well as to characterize how CB use interacts with that relationship. [ABSTRACT FROM AUTHOR]

Purpose: A novel software algorithm combining non-invasive EEG and resting state functional MRI data to map networks of cortex correlated to epileptogenic tissue was used to map an epilepsy network non-invasively. The relationship between epilepsy network connectivity and outcomes after surgery was investigated using this non-invasive and non-concurrent modeling algorithm.Method: Scalp EEG and resting state functional MRI were acquired for nineteen patients with temporal lobe epilepsy. The hypothetical irritative zone was mapped, and resting state functional MRI data was used to model regions functionally correlated with the irritative zone. Epilepsy network connectivity was measured in patient with temporal lobe epilepsy (n = 19) both pre- and post-operatively. Temporal networks were also mapped in healthy control participants (n = 6).Results: Thirteen of nineteen patients (68 %) were seizure free after 20.3 ± 4.8 months. Epilepsy network connectivity within the temporal lobe was significantly higher among patients with temporal lobe epilepsy compared to the healthy control patients (p < 0.05). Disconnection of the epilepsy network was significantly higher in patients who were seizure free. Using spearman rho analyses, neuropsychological function after surgery was found to be relatively better in patients with higher degree of epilepsy network disconnection.Conclusions: The magnitude of network disconnection after surgery was strongly associated with increased rates of seizure freedom and relatively better neuropsychological measures of memory and naming function. It was shown that seizure-free outcomes and relatively improved neuropsychological function correlated with surgical disconnection of a highly synchronous epilepsy network. [ABSTRACT FROM AUTHOR]

Background: The mesial prefrontal cortex, cingulate cortex, and the ventral striatum are key nodes of the human mesial fronto-striatal circuit involved in decision-making and executive function and pathological disorders. Here we ask whether deep wide-field repetitive transcranial magnetic stimulation (rTMS) targeting the mesial prefrontal cortex (MPFC) influences resting state functional connectivity.Methods: In Study 1, we examined functional connectivity using resting state multi-echo and independent components analysis in 154 healthy subjects to characterize default connectivity in the MPFC and mid-cingulate cortex (MCC). In Study 2, we used inhibitory, 1 Hz deep rTMS with the H7-coil targeting MPFC and dorsal anterior cingulate (dACC) in a separate group of 20 healthy volunteers and examined pre- and post-TMS functional connectivity using seed-based and independent components analysis.Results: In Study 1, we show that MPFC and MCC have distinct patterns of functional connectivity with MPFC–ventral striatum showing negative, whereas MCC–ventral striatum showing positive functional connectivity. Low-frequency rTMS decreased functional connectivity of MPFC and dACC with the ventral striatum. We further showed enhanced connectivity between MCC and ventral striatum.Conclusions: These findings emphasize how deep inhibitory rTMS using the H7-coil can influence underlying network functional connectivity by decreasing connectivity of the targeted MPFC regions, thus potentially enhancing response inhibition and decreasing drug-cue reactivity processes relevant to addictions. The unexpected finding of enhanced default connectivity between MCC and ventral striatum may be related to the decreased influence and connectivity between the MPFC and MCC. These findings are highly relevant to the treatment of disorders relying on the mesio-prefrontal-cingulo-striatal circuit.

Novel and valuable objects are motivationally attractive for animals including primates. However, little is known about how novelty and value processing is organized across the brain. We used fMRI in macaques to map brain responses to visual fractal patterns varying in either novelty or value dimensions and compared the results with the structure of functionally connected brain networks determined at rest. The results show that different brain networks possess unique combinations of novelty and value coding. One network identified in the ventral temporal cortex preferentially encoded object novelty, whereas another in the parietal cortex encoded the learned value. A third network, broadly composed of temporal and prefrontal areas (TP network), along with functionally connected portions of the striatum, amygdala, and claustrum, encoded both dimensions with similar activation dynamics. Our results support the emergence of a common currency signal in the TP network that may underlie the common attitudes toward novel and valuable objects. [ABSTRACT FROM AUTHOR]

Background: Children born very preterm often display selective cognitive difficulties at school age even in the absence of major brain injury. Alterations in neurophysiological activity underpinning such difficulties, as well as their relation to specific aspects of adverse neonatal experience, remain poorly understood. In the present study, we examined interregional connectivity and spectral power in very preterm children at school age, and their relationship with clinical neonatal variables and long‐term outcomes (IQ, executive functions, externalizing/internalizing behavior, visual‐motor integration). Methods: We collected resting state magnetoencephalographic (MEG) and psychometric data from a cohort at the age of 8 years followed prospectively since birth, which included three groups: Extremely Low Gestational Age (ELGA, 24–28 weeks GA n = 24, age 7.7 ± 0.38, 10 girls), Very Low Gestational Age (VLGA, 29–32 weeks GA n = 37, age 7.7 ± 0.39, 24 girls), and full‐term children (38–41 weeks GA n = 39, age 7.9 ± 1.02, 24 girls). Interregional phase synchrony and spectral power were tested for group differences, and associations with neonatal and outcome variables were examined using mean‐centered and behavioral Partial Least Squares (PLS) analyses, respectively. Results: We found greater connectivity in the theta band in the ELGA group compared to VLGA and full‐term groups, primarily involving frontal connections. Spectral power analysis demonstrated overall lower power in the ELGA and VLGA compared to full‐term group. PLS indicated strong associations between neurophysiological connectivity at school age, adverse neonatal experience and cognitive performance, and behavior. Resting spectral power was associated only with behavioral scores. Conclusions: Our findings indicate significant atypicalities of neuromagnetic brain activity and connectivity in very preterm children at school age, with alterations in connectivity mainly observed only in the ELGA group. We demonstrate a significant relationship between connectivity, adverse neonatal experience, and long‐term outcome, indicating that the disruption of developing neurophysiological networks may mediate relationships between neonatal events and cognitive and behavioral difficulties at school age. [ABSTRACT FROM AUTHOR]

Background: The mesial prefrontal cortex, cingulate cortex, and the ventral striatum are key nodes of the human mesial fronto-striatal circuit involved in decision-making and executive function and pathological disorders. Here we ask whether deep wide-field repetitive transcranial magnetic stimulation (rTMS) targeting the mesial prefrontal cortex (MPFC) influences resting state functional connectivity. Methods: In Study 1, we examined functional connectivity using resting state multi-echo and independent components analysis in 154 healthy subjects to characterize default connectivity in the MPFC and mid-cingulate cortex (MCC). In Study 2, we used inhibitory, 1 Hz deep rTMS with the H7-coil targeting MPFC and dorsal anterior cingulate (dACC) in a separate group of 20 healthy volunteers and examined pre- and post-TMS functional connectivity using seed-based and independent components analysis. Results: In Study 1, we show that MPFC and MCC have distinct patterns of functional connectivity with MPFC–ventral striatum showing negative, whereas MCC–ventral striatum showing positive functional connectivity. Low-frequency rTMS decreased functional connectivity of MPFC and dACC with the ventral striatum. We further showed enhanced connectivity between MCC and ventral striatum. Conclusions: These findings emphasize how deep inhibitory rTMS using the H7-coil can influence underlying network functional connectivity by decreasing connectivity of the targeted MPFC regions, thus potentially enhancing response inhibition and decreasing drug-cue reactivity processes relevant to addictions. The unexpected finding of enhanced default connectivity between MCC and ventral striatum may be related to the decreased influence and connectivity between the MPFC and MCC. These findings are highly relevant to the treatment of disorders relying on the mesio-prefrontal-cingulo-striatal circuit. [ABSTRACT FROM AUTHOR]

Cannabis produces a broad range of acute, dose-dependent psychotropic effects. Only a limited number of neuroimaging studies have mapped these effects by examining the impact of cannabis on resting state brain neurophysiology. Moreover, how genetic variation influences the acute effects of cannabis on resting state brain function is unknown. Here we investigated the acute effects of ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on resting state brain neurophysiology, and their modulation by catechol-methyl-transferase (COMT) Val158Met genotype. Thirty-nine healthy volunteers participated in a pharmacological MRI study, where we applied Arterial Spin Labelling (ASL) to measure perfusion and functional MRI to assess resting state connectivity. THC increased perfusion in bilateral insula, medial superior frontal cortex, and left middle orbital frontal gyrus. This latter brain area showed significantly decreased connectivity with the precuneus after THC administration. THC effects on perfusion in the left insula were significantly related to subjective changes in perception and relaxation. These findings indicate that THC enhances metabolism and thus neural activity in the salience network. Furthermore, results suggest that recruitment of brain areas within this network is involved in the acute effects of THC. Resting state perfusion was modulated by COMT genotype, indicated by a significant interaction effect between drug and genotype on perfusion in the executive network, with increased perfusion after THC in Val/Met heterozygotes only. This finding suggests that prefrontal dopamine levels are involved in the susceptibility to acute effects of cannabis. [ABSTRACT FROM AUTHOR]

Abstract Foreign language learning in adulthood often takes place in classrooms where learning outcomes vary widely among students, for both initial learning and long-term retention. Despite the fundamental role of speech perception in first language acquisition, its role in foreign language learning outcomes remains unknown. Using a speech discrimination functional magnetic resonance imaging (fMRI) task and resting-state fMRI before and after an intensive, classroom-based, Mandarin Chinese course, we examined how variations in pre-training organization and pre-to-post reorganization of brain functions predicted successful language learning in male and female native English-speakers. Greater pre-training activation in right inferior frontal gyrus (IFG) to Mandarin speech was associated with better Mandarin attainment at the end of the course. After four weeks of class, learners showed overall increased activation in left IFG and left superior parietal lobule (SPL) to Mandarin speech, but in neither region was variation related to learning outcomes. Immediate attainment was associated with greater pre-to-post reduction of right IFG activation to Mandarin speech but also greater enhancement of resting-state connectivity between this region and both left IFG and left SPL. Long-term retention of Mandarin skills measured three months later was more accurately predicted by models using features of neural preparedness (pre-training activation) and neural plasticity (pre-to-post activation change) than models using behavior preparedness and plasticity features (pre-training speech discrimination accuracy and Mandarin attainment, respectively). These findings suggest that successful holistic foreign language acquisition in human adulthood requires right IFG engagement during initial learning but right IFG disengagement for long-term retention of language skills. Highlights ● Brain organization of speech perception affects whole language learning in adults. ● Right-to-left-hemisphere functional transition after a 4-week Mandarin course. ● Initial engagement and later disengagement of right IFG predict long-term retention. ● Enhanced cross-hemispheric resting-state connectivity found in successful learners. [ABSTRACT FROM AUTHOR]

Parkinson's disease is primarily characterized by diminished dopaminergic function; however, the impact of these impairments on large-scale brain dynamics remains unclear. It has been difficult to disentangle the direct effects of Parkinson's disease from compensatory changes that reconfigure the functional signature of the whole brain network. To examine the causal role of dopamine depletion in network-level topology, we investigated time-varying network structure in 37 individuals with idiopathic Parkinson's disease, both ON and OFF dopamine replacement therapy, along with 50 age-matched, healthy control subjects using resting state functional MRI. By tracking dynamic network-level topology, we found that the Parkinson's disease OFF state was associated with greater network-level integration than in the ON state. The extent of integration in the OFF state inversely correlated with motor symptom severity, suggesting that a shift toward a more integrated network topology may be a compensatory mechanism associated with preserved motor function in the dopamine depleted OFF state. Furthermore, we were able to demonstrate that measures of both cognitive and brain reserve (i.e. premorbid intelligence and whole brain grey matter volume) had a positive relationship with the relative increase in network integration observed in the dopaminergic OFF state. This suggests that each of these factors plays an important role in promoting network integration in the dopaminergic OFF state. Our findings provide a mechanistic basis for understanding the Parkinson's disease OFF state and provide a further conceptual link with network-level reconfiguration. Together, our results highlight the mechanisms responsible for pathological and compensatory change in Parkinson's disease. [ABSTRACT FROM AUTHOR]

Abstract Background The experience of auditory verbal hallucinations in schizophrenia is associated with changes in brain network function. In particular, studies indicate altered functional coupling between nodes of the language and default mode networks. Neurofeedback based on real-time functional magnetic resonance imaging (rtfMRI) can be used to modulate such aberrant network connectivity. Methods We investigated resting-state connectivity changes after neurofeedback (NF) in 21 patients with schizophrenia and 35 healthy individuals. All participants underwent two days of neurofeedback training of important nodes of the left-hemispheric language network including the inferior frontal gyrus (IFG) and posterior superior temporal gyrus (pSTG). In a double-blind randomized cross-over design, participants learned to down- and up-regulate their brain activation in the designated target regions based on NF. Prior to and after each training day, a resting state measurement took place. Results Coupling between nodes of the language and the default mode network (DMN) selectively increased after down-as compared to up-regulation NF. Network analyses revealed more pronounced increases in functional connectivity between nodes of the language network and the DMN in patients compared to healthy individuals. In particular, down-regulation NF led to increased coupling between nodes of the language network and bilateral inferior parietal lobe (IPL) as well as posterior cingulate cortex (PCC)/precuneus in patients. Up-regulation strengthened connectivity with the medial prefrontal cortex (mPFC). Improved well-being four weeks after the training predicted increased functional coupling between the left IFG and left IPL. Conclusion Modulatory effects emerged as increased internetwork communication, indicating that down-regulation NF selectively enhances coupling between language and DM network nodes in patients with AVH. RtfMRI NF may thus be used to modulate brain network function that is relevant to the phenomenology of AVH. Specific effects of self-regulation on symptom improvement have to be explored in therapeutic interventions. [ABSTRACT FROM AUTHOR]

Resting state (RS) connectivity has been increasingly studied in healthy and diseased brains in humans and animals. This paper presents a new method to analyze RS data from fMRI that combines multiple seed correlation analysis with graph-theory (MSRA). We characterize and evaluate this new method in relation to two other graph-theoretical methods and ICA. The graph-theoretical methods calculate cross-correlations of regional average time-courses, one using seed regions of the same size (SRCC) and the other using whole brain structure regions (RCCA). We evaluated the reproducibility, power, and capacity of these methods to characterize short-term RS modulation to unilateral physiological whisker stimulation in rats. Graph-theoretical networks found with the MSRA approach were highly reproducible, and their communities showed large overlaps with ICA components. Additionally, MSRA was the only one of all tested methods that had the power to detect significant RS modulations induced by whisker stimulation that are controlled by family-wise error rate (FWE). Compared to the reduced resting state network connectivity during task performance, these modulations implied decreased connectivity strength in the bilateral sensorimotor and entorhinal cortex. Additionally, the contralateral ventromedial thalamus (part of the barrel field related lemniscal pathway) and the hypothalamus showed reduced connectivity. Enhanced connectivity was observed in the amygdala, especially the contralateral basolateral amygdala (involved in emotional learning processes). In conclusion, MSRA is a powerful analytical approach that can reliably detect tiny modulations of RS connectivity. It shows a great promise as a method for studying RS dynamics in healthy and pathological conditions.

Fear extinction is a powerful model of adaptive and anxiety-related maladaptive fear inhibition. This learning process is dependent upon plastic interactions between the amygdala, the anterior midcingulate cortex (aMCC), the hippocampus, and the ventromedial prefrontal cortex (vmPFC). With regard to the amygdala, the basolateral (BLA) and centromedial amygdala (CMA) serve unique roles in fear extinction. In a large sample (N = 91), the current study examined pre- to post-extinction changes in resting state functional connectivity (RSFC) of fear inhibition and expression pathways. We also examined how trait anxiety and extinction performance were associated with extinction-related changes within these neural pathways. We found stronger pre- to post-extinction RSFC in pathways known to play a role in the down-regulation of fear responses (BLA-hippocampus, aMCC-hippocampus, CMA-hippocampus, CMA-aMCC). We also found that trait anxiety was associated with strengthening of a BLA–aMCC circuit supporting fear expression following extinction learning. Furthermore, we found that physiological indices of poorer extinction learning were linked to weaker pre- to post-extinction RSFC of a BLA–hippocampus pathway important for fear extinction consolidation. Our results highlight the network changes that occur during extinction, the separable role of CMA and BLA-based circuitry and a key pathway linked to risk for anxiety pathology. [ABSTRACT FROM AUTHOR]

Resting state (RS) connectivity has been increasingly studied in healthy and diseased brains in humans and animals. This paper presents a new method to analyze RS data from fMRI that combines multiple seed correlation analysis with graph-theory (MSRA). We characterize and evaluate this new method in relation to two other graph-theoretical methods and ICA. The graph-theoreticalmethods calculate cross-correlations of regional average time-courses, one using seed regions of the same size (SRCC) and the other using whole brain structure regions (RCCA). We evaluated the reproducibility, power, and capacity of these methods to characterize short-term RS modulation to unilateral physiological whisker stimulation in rats. Graph-theoretical networks found with the MSRA approach were highly reproducible, and their communities showed large overlaps with ICA components. Additionally, MSRA was the only one of all tested methods that had the power to detect significant RS modulations induced by whisker stimulation that are controlled by family-wise error rate (FWE). Compared to the reduced resting state network connectivity during task performance, these modulations implied decreased connectivity strength in the bilateral sensorimotor and entorhinal cortex. Additionally, the contralateral ventromedial thalamus (part of the barrel field related lemniscal pathway) and the hypothalamus showed reduced connectivity. Enhanced connectivity was observed in the amygdala, especially the contralateral basolateral amygdala (involved in emotional learning processes). In conclusion, MSRA is a powerful analytical approach that can reliably detect tiny modulations of RS connectivity. It shows a great promise as a method for studying RS dynamics in healthy and pathological conditions. [ABSTRACT FROM AUTHOR]

Objective: In this pilot study, the purpose is to investigate if a series of sphenopalatine ganglion (SPG) blockade treatments modulate the functional connectivity within the salience and central executive network (CEN) in chronic migraine with medication overuse headaches (CMw/MOH). Background: Using intranasal local anesthesia to block the SPG for the treatment of various headache disorders has been employed in clinical practice since the early 1900s. However, the exact mechanism of how SPG modulate resting state intrinsic functional brain networks connectivity remains to be elucidated. This pilot study seeks to understand the resting state connectivity changes in salience and CENs, with emphasis on the mesocorticolimbic systems, before and after a series of SPG block treatments. Methods: Using fMRI, resting state connectivity was derived from predefined networks of nodes (regions of interests) for the salience (27 nodes, 351 connections) and CENs (17 nodes, 136 connections). After treatments, a paired samples t‐test (with 10,000 permutations to correct for multiple comparison) was used to evaluate changes in the intranetwork resting state functional connectivity within the salience and executive networks, as well as the overall network connectivity strength. Results: When comparing connectivity strength at baseline to that at the end of treatment in our cohort of 10 CMw/MOH participants, there were several connections within the salience (n = 9) and executive (n = 8) networks that were significantly improved. Within the salience network, improved connectivity was observed between the prefrontal cortex and various regions of the insula, basal ganglia, motor, and frontal cortex. Additionally, changes in connectivity were observed between regions of the temporal cortex with the basal ganglia and supramarginal gyrus. Within the CEN, improved connectivity was observed between the prefrontal cortex and regions of the anterior thalamus, caudate, and frontal cortex. After treatment, the overall CEN connectivity was significantly improved (Baseline 0.00 ± 0.08; 6 weeks 0.03 ± 0.09, P = .01); however, the overall salience network connectivity was not significantly improved (Baseline −0.01 ± 0.10; 6 weeks 0.01 ± 0.12, P = .26). Additionally, after treatment, there was a significant reduction in the number of moderate/severe headache days per month (Baseline 21.1 ± 6.6; 6 weeks 11.2 ± 6.5, P < .001), HIT‐6 (Baseline 66.1 ± 2.6; 6 weeks 60.2 ± 3.6, P < .001), and PHQ‐9 (Baseline 12.4 ± 5.7; 6 weeks 6.1 ± 3.6, P = .008) scores. Conclusion: In this longitudinal fMRI study, we observed improved functional connectivity within both networks, primarily involving connectivity between regions of the prefrontal cortex and limbic (cortical‐limbic) structures, and between different cortical (cortical‐cortical) regions after a series of repetitive SPG blockades. The overall CEN strength was also improved. Our results suggest that recurrent parasympathetic inhibition via SPG is associated with improved functional connectivity in brain regions critical to pain processing in CMw/MOH. [ABSTRACT FROM AUTHOR]

Machine learning techniques have become increasingly popular in the field of resting state fMRI (functional magnetic resonance imaging) network based classification. However, the application of convolutional networks has been proposed only very recently and has remained largely unexplored. In this paper we describe a convolutional neural network architecture for functional connectome classification called connectome-convolutional neural network (CCNN). Our results on simulated datasets and a publicly available dataset for amnestic mild cognitive impairment classification demonstrate that our CCNN model can efficiently distinguish between subject groups. We also show that the connectome-convolutional network is capable to combine information from diverse functional connectivity metrics and that models using a combination of different connectivity descriptors are able to outperform classifiers using only one metric. From this flexibility follows that our proposed CCNN model can be easily adapted to a wide range of connectome based classification or regression tasks, by varying which connectivity descriptor combinations are used to train the network.

Cocaine addiction is characterized by notoriously high relapse rates following treatment. Recent efforts to address poor treatment outcomes have turned to potential neural markers of relapse risk. Accordingly, the present study examined resting state functional connectivity (rsFC) within and between three large-scale cortical networks: the default mode network (DMN), salience network (SN) and executive control network (ECN). All three have been implicated in relapse-related phenomena including craving, withdrawal and executive control deficits. Forty-five cocaine-dependent individuals and 22 healthy controls completed 6-min resting fMRI scans, The Wisconsin Card Sorting Task, Continuous Performance Test and Cocaine Craving Questionnaire. Cocaine-dependent individuals completed all measures in the final week of a residential treatment episode. Ten control and 9 abstinent cocaine-dependent individuals returned for 3-6 month follow-up scan visits. A group-level independent component analysis was employed to generate ECN, DMN and SN components. For individuals abstinent up to day 30 post-treatment (n = 21), we found enhanced pre-discharge rsFC between the left ECN and both the right ECN and SN as well as between the right ECN and left ECN. Left ECN rsFC effects remained elevated 3-6 months later among abstinent cocaine-dependent individuals. Relapse was related to fewer years of education and more years smoking but no other demographic, clinical, treatment and neurocognitive characteristics. Findings suggest that interhemispheric ECN and ECN-SN connectivity strength may protect against relapse to cocaine use following treatment. These patterns of enhanced interhemispheric network connectivity may reflect a greater capacity to engage executive control processes when faced with opportunities to use cocaine post-treatment. [ABSTRACT FROM AUTHOR]

Machine learning techniques have become increasingly popular in the field of resting state fMRI (functional magnetic resonance imaging) network based classification. However, the application of convolutional networks has been proposed only very recently and has remained largely unexplored. In this paper we describe a convolutional neural network architecture for functional connectome classification called connectomeconvolutional neural network (CCNN). Our results on simulated datasets and a publicly available dataset for amnestic mild cognitive impairment classification demonstrate that our CCNN model can efficiently distinguish between subject groups. We also show that the connectome-convolutional network is capable to combine information from diverse functional connectivity metrics and that models using a combination of different connectivity descriptors are able to outperform classifiers using only one metric. From this flexibility follows that our proposed CCNN model can be easily adapted to a wide range of connectome based classification or regression tasks, by varying which connectivity descriptor combinations are used to train the network. [ABSTRACT FROM AUTHOR]

The default mode network (DMN) encompasses brain systems that exhibit coherent neural activity at rest. DMN brain systems have been implicated in diverse social, cognitive, and affective processes, as well as risk for forms of dementia and psychiatric disorders that associate with systemic inflammation. Areas of the anterior cingulate cortex (ACC) and surrounding medial prefrontal cortex (mPFC) within the DMN have been implicated specifically in regulating autonomic and neuroendocrine processes that relate to systemic inflammation via bidirectional signaling mechanisms. However, it is still unclear whether indicators of inflammation relate directly to coherent resting state activity of the ACC, mPFC, or other areas within the DMN. Accordingly, we tested whether plasma interleukin (IL)-6, an indicator of systemic inflammation, covaried with resting-state functional connectivity of the DMN among 98 adults aged 30-54 (39% male; 81% Caucasian). Independent component analyses were applied to resting state fMRI data to generate DMN connectivity maps. Voxel-wise regression analyses were then used to test for associations between IL-6 and DMN connectivity across individuals, controlling for age, sex, body mass index, and fMRI signal motion. Within the DMN, IL-6 covaried positively with connectivity of the sub-genual ACC and negatively with a region of the dorsal medial PFC at corrected statistical thresholds. These novel findings offer evidence for a unique association between a marker of systemic inflammation (IL-6) and ACC and mPFC functional connectivity within the DMN, a network that may be important for linking aspects of immune function to psychological and behavioral states in health and disease. [ABSTRACT FROM AUTHOR]

Cognitive deficits are common in Parkinson's disease and we suspect that dysfunctions of connected brain regions can be the source of these deficits. The aim of the present study was to investigate changes in whole-brain intrinsic functional connectivity according to differences in cognitive profiles in Parkinson's disease. 119 participants were enrolled and divided into four groups according to their cognitive phenotypes (determined by a cluster analysis): (i) 31 cognitively intact patients ( G1), (ii) 31 patients with only slight mental slowing ( G2), (iii) 43 patients with mild to moderate deficits mainly in executive functions ( G3), (iv) 14 patients with severe deficits in all cognitive domains ( G4-5). Rs-fMRI whole-brain connectivity was examined by two complementary approaches: graph theory for studying network functional organization and network-based statistics (NBS) for exploring functional connectivity amongst brain regions. After adjustment for age, duration of formal education and center of acquisition, there were significant group differences for all functional organization indexes: functional organization decreased ( G1 > G2 > G3 > G4-5) as cognitive impairment worsened. Between-group differences in functional connectivity (NBS corrected, P < 0.01) mainly concerned the ventral prefrontal, parietal, temporal and occipital cortices as well as the basal ganglia. In Parkinson's disease, brain network organization is progressively disrupted as cognitive impairment worsens, with an increasing number of altered connections between brain regions. We observed reduced connectivity in highly associative areas, even in patients with only slight mental slowing. The association of slowed mental processing with loss of connectivity between highly associative areas could be an early marker of cognitive impairment in Parkinson's disease and may contribute to the detection of prodromal forms of Parkinson's disease dementia. Hum Brain Mapp 38:1604-1621, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In recent decades, the primary intention of neuroscientists and psychiatrics is to evaluate the connectivity between brain regions and psychiatric disorders. The amygdala has central immersion in memory alliance, stress response, emotional perception, and automatic responses to emotional stimuli. This paper uses a meta-analysis approach to establish the relationship between structural resting state and functional amygdala connectivity with depression and suicide ideation with suicide behavior. In addition, this study explores the moderating effect of patients' demographic characteristics (gender and age) based on 30 studies. The results show that structural amygdala connectivity is positively related to the instability of depression, while for resting and task functional connectivity amygdala shows a significant negative connection with depression. Furthermore, the amygdala showed a partial activation for non-suicide self-injuries and suicide ideation. From structural and functional magnetic imaging, the current findings also support the moderating effect of the age of the participants on the amygdala connectivity with psychiatric conditions. Generally, amygdala connectivity with psychiatric disorders was not significantly moderate with the role of gender, however, this study enhances the existing hypothetical review articles and confirms the connectivity of the psychological condition with the amygdala region. It concludes that the amygdala plays a vital role in regulating and responding to emotions. [ABSTRACT FROM AUTHOR]