Higher Resting-state Functional Connectivity Research Articles

Examining putamen resting-state connectivity markers of suicide attempt history in depressed adolescents.

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. 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). 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, cluster-wise 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. 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.

Altered Reward Circuit Function Moderates the Relationship between Childhood Maltreatment and Depression Severity in Adolescents

Background. The role of childhood maltreatment (CM) is believed to be crucial in the aberrant function of reward circuit in adolescent-onset major depressive disorder (AO-MDD). Nevertheless, the impact of abnormalities in the GP-based reward circuit on the association between CM and the severity of AO-MDD remains largely unknown. Methods. The GP-based resting-state functional connectivity (RSFC) was analyzed in a sample of 75 patients with AO-MDD and 80 healthy controls in order to identify potential abnormalities in the GP-based reward circuit in AO-MDD patients. Furthermore, we investigated the possible associations between aberrant GP-based reward circuit functioning, CM and its subtypes (namely, childhood abuse and childhood neglect), and the severity of AO-MDD. Results. Compared to the healthy control group, patients with AO-MDD demonstrated a reduction in RSFC between the left posterior GP and the right dorsomedial prefrontal cortex (DMPFC). Our moderation analysis revealed that the abnormal RSFC between the posterior GP and DMPFC had a moderating effect on the relationship between CM and the severity of AO-MDD. Furthermore, upon further interaction decomposition, we observed a positive correlation between CM and AO-MDD severity exclusively in patients with AO-MDD who exhibited lower RSFC between the posterior GP and DMPFC. For AO-MDD patients with higher RSFC between posterior GP and DMPFC, the relationship between CM and AO-MDD severity was not discernible. Conclusions. Our findings underscore the crucial role of anomalies in the reward circuit in AO-MDD and furnish novel leads for probing the relationship among CM, malfunctioning of the reward circuit, and AO-MDD.

Negative affective burden is associated with higher resting-state functional connectivity in subjective cognitive decline

Subjective cognitive decline (SCD), as expressed by older adults, is associated with negative affect, which, in turn, is a likely risk factor for Alzheimer’s Disease (AD). This study assessed the associations between negative affective burden, cognitive functioning, and functional connectivity in networks vulnerable to AD in the context of SCD. Older participants (60–90 years) with SCD (n = 51) and healthy controls (n = 50) were investigated in a cross-sectional study. Subclinical negative affective burden, quantified through a composite of self-reported negative affective factors, was related to cognitive functioning (self-perceived and objective) and functional connectivity. Seed-to-voxel analyses were carried out in default mode network (DMN) and salience network (SAL) nodes using resting-state functional magnetic resonance imaging. Greater negative affective burden was associated with lower self-perceived cognitive functioning and lower between-network functional connectivity of DMN and SAL nodes in the total sample. In addition, there was a significant moderation of SCD status. Greater negative affective burden related to higher functional connectivity within DMN (posterior cingulate-to-precuneus) and within SAL (anterior cingulate-to-insula) nodes in the SCD group, whereas in controls the inverse association was found. We show that negative affective burden is associated with functional brain alterations in older adults, regardless of SCD status. Specifically in the SCD phenotype, greater negative affective burden relates to higher functional connectivity within brain networks vulnerable to AD. Our findings imply that negative affective burden should be considered a potentially modifiable target for early intervention.

To explore the mechanism of tobacco addiction using structural and functional MRI: a preliminary study of the role of the cerebellum-striatum circuit.

Previous studies have found that the striatum and the cerebellum played important roles in nicotine dependence, respectively. In heavy smokers, however, the effect of resting-state functional connectivity of cerebellum-striatum circuits in nicotine dependence remained unknown. This study aimed to explore the role of the circuit between the striatum and the cerebellum in addiction in heavy smokers using structural and functional magnetic resonance imaging. The grey matter volume differences and the resting-state functional connectivity differences in cerebellum-striatum circuits were investigated between 23 heavy smokers and 23 healthy controls. The cigarette dependence in heavy smokers and healthy controls were evaluated by using Fagerström Test. Then, we applied mediation analysis to test whether the resting-state functional connectivity between the striatum and the cerebellum mediates the relationship between the striatum morphometry and the nicotine dependence in heavy smokers. Compared with healthy controls, the heavy smokers' grey matter volumes decreased significantly in the cerebrum (bilateral), and increased significantly in the caudate (bilateral). Seed-based resting-state functional connectivity analysis showed significantly higher resting-state functional connectivity among the bilateral caudate, the left cerebellum, and the right middle temporal gyrus in heavy smokers. The cerebellum-striatum resting-state functional connectivity fully mediated the relationship between the striatum morphometry and the nicotine dependence in heavy smokers. Heavy smokers showed abnormal interactions and functional connectivity between the striatum and the cerebellum, which were associated with the striatum morphometry and nicotine dependence. Such findings could provide new insights into the neural correlates of nicotine dependence in heavy smokers.

Abnormality of Resting-State Functional Connectivity in Major Depressive Disorder: A Study With Whole-Head Near-Infrared Spectroscopy.

Near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that has advantages in clinical usage. Previous functional magnetic resonance imaging (fMRI) studies have found that the resting-state functional connectivity (RSFC) of the default mode network (DMN) is increased, while the RSFC of the cognitive control network (CCN) is reduced in patients with major depressive disorder (MDD) compared with healthy controls. This study tested whether the NIRS-based RSFC measurements can detect the abnormalities in RSFC that have been associated with MDD in previous fMRI studies. We measured 8 min of resting-state brain activity in 34 individuals with MDD and 78 age- and gender-matched healthy controls using a whole-head NIRS system. We applied a previously established partial correlation analysis for estimating RSFCs between the 17 cortical regions. We found that MDD patients had a lower RSFC between the left dorsolateral prefrontal cortex and the parietal lobe that comprise the CCN, and a higher RSFC between the right orbitofrontal cortex and ventrolateral prefrontal cortex, compared to those in healthy controls. The RSFC strength of the left CCN was negatively correlated with the severity of depressive symptoms and the dose of antipsychotic medication and positively correlated with the level of social functioning. The results of this study suggest that NIRS-based measurements of RSFCs have potential clinical applications.

Pretreatment Reward Sensitivity and Frontostriatal Resting-State Functional Connectivity Are Associated With Response to Bupropion After Sertraline Nonresponse

BackgroundStandard guidelines recommend selective serotonin reuptake inhibitors as first-line antidepressants for adults with major depressive disorder, but success is limited and patients who fail to benefit are often switched to non–selective serotonin reuptake inhibitor agents. This study investigated whether brain- and behavior-based markers of reward processing might be associated with response to bupropion after sertraline nonresponse. MethodsIn a two-stage, double-blinded clinical trial, 296 participants were randomized to receive 8 weeks of sertraline or placebo in stage 1. Individuals who responded continued on another 8-week course of the same intervention in stage 2, while sertraline and placebo nonresponders crossed over to bupropion and sertraline, respectively. Data from 241 participants were analyzed. The stage 2 sample comprised 87 patients with major depressive disorder who switched medication and 38 healthy control subjects. A total of 116 participants with major depressive disorder treated with sertraline in stage 1 served as an independent replication sample. The probabilistic reward task and resting-state functional magnetic resonance imaging were administered at baseline. ResultsGreater pretreatment reward sensitivity and higher resting-state functional connectivity between bilateral nucleus accumbens and rostral anterior cingulate cortex were associated with positive response to bupropion but not sertraline. Null findings for sertraline were replicated in the stage 1 sample. ConclusionsPretreatment reward sensitivity and frontostriatal connectivity may identify patients likely to benefit from bupropion following selective serotonin reuptake inhibitor failures. Results call for a prospective replication based on these biomarkers to advance clinical care.

Ketamine normalizes subgenual cingulate cortex hyper-activity in depression.

Mounting evidence supports the rapid antidepressant efficacy of the N-methyl-D-aspartate receptor antagonist, ketamine, for treating major depressive disorder (MDD); however, its neural mechanism of action remains poorly understood. Subgenual anterior cingulate cortex (sgACC) hyper-activity during rest has been consistently implicated in the pathophysiology of MDD, potentially driven in partby excessive hippocampal gluatmatergic efferents to sgACC. Reduction of sgACC activity has been associated with successful antidepressant treatment. This study aimed to examine whether task-based sgACC activity was higher in patients with MDD compared to controls and to determine whether this activity was altered by single-dose ketamine. In Study 1, patients with MDD (N = 28) and healthy controls (N = 20) completed task-based functional magnetic resonance imaging using an established incentive-processing task. In Study 2, a second cohort of patients with MDD (N = 14) completed the same scanning protocol at baseline and following a 40 min infusion of ketamine (0.5 mg/kg). Task-based activation of sgACC was examined with a seed-driven analysis assessing group differences and changes from pre to post treatment. Patients with MDD showed higher sgACC activation to positive and negative monetary incentives compared to controls, associated with anhedonia and anxiety, respectively. In addition, patients with MDD had higher resting-state functional connectivity between hippocampus and sgACC, associated with sgACC hyper-activation to positive incentives, but not negative incentives. Finally, ketamine reduced sgACC hyper-activation to positive incentives, but not negative incentives. These findings suggest a neural mechanism by which ketamine exerts its antidepressant efficacy, via rapid blunting of aberrant sgACC hyper-reactivity to positive incentives.

Individual susceptibility to TMS affirms the precuneal role in meta-memory upon recollection.

A recent virtual-lesion study using inhibitory repetitive transcranial magnetic stimulation (rTMS) confirmed the causal behavioral relevance of the precuneus in the evaluation of one's own memory performance (aka mnemonic metacognition). This study's goal is to elucidate how these TMS-induced neuromodulatory effects might relate to the neural correlates and be modulated by individual anatomical profiles in relation to meta-memory. In a within-subjects design, we assessed the impact of 20-min rTMS over the precuneus, compared to the vertex, across three magnetic resonance imaging (MRI) neuro-profiles on 18 healthy subjects during a memory versus a perceptual task. Task-based functional MRI revealed that BOLD signal magnitude in the precuneus is associated with variation in individual meta-memory efficiency. Moreover, individuals with higher resting-state functional connectivity (rs-fcMRI) between the precuneus and the hippocampus, or smaller gray matter volume in the stimulated precuneal region exhibit considerably higher vulnerability to the TMS effect. These effects were not observed in the perceptual domain. Thus, we provide compelling evidence in outlining a possible circuit encompassing the precuneus and its mnemonic midbrain neighbor the hippocampus at the service of realizing our meta-awareness during memory recollection of episodic details.

Resting-state functional connectivity in medication-naïve adolescents with major depressive disorder

Adolescence is a vulnerable period for major depressive disorder (MDD). The aim of our study was to investigate resting-state functional connectivity (RSFC) in first-episode, medication-naïve adolescent MDD patients. Twenty-three drug-naïve adolescents diagnosed with first-episode MDD and 27 healthy participants were enrolled. Seed-to-voxel RSFC analyses were performed. The frontolimbic circuit regions of interest included the amygdala, anterior cingulate cortex, insula, and hippocampus. A correlation analysis between the RSFC and Children's Depression Inventory, Hamilton depression rating scale, and duration of episodes was performed. The adolescents with MDD exhibited the following characteristics: a lower RSFC between the right amygdala and right superior frontal gyrus; a lower RSFC between the right hippocampus and clusters including the right insula and right middle frontal gyrus; a higher RSFC between the left insula and clusters including the bilateral middle frontal gyrus, right superior frontal gyrus, and right frontal pole; and a higher RSFC between the left dorsal anterior cingulate cortex and a cluster including the left insula. Medication-naïve adolescents with depression display lower connectivity of several brain regions implicated in processing, regulation, and memory of emotions. Higher connectivity was observed in brain regions that potentially explain rumination, impaired concentration, and physiological arousal.

Higher resting state functional connectivity between the vmPFC and rTPJ in individuals who display conversational synchrony

Abstract The neural mechanisms that support synchrony of conversational behaviors (e.g., word production, turn length) are not well understood. Lesion work has suggested that the ventromedial prefrontal cortex (vmPFC) is important for noncontent speech convergence, which measures if word production becomes more similar across a conversation (Gordon, Tranel, & Duff, 2014). However, the relationship between neural activity and conversational synchrony has not been studied in healthy individuals and it is not known if differences in neural activity contribute to individual differences in conversational behavior. In this preliminary study, we assessed noncontent speech convergence in twenty female undergraduates who conversed with an unfamiliar conversational partner for 20 min. Ten dyads displayed noncontent speech convergence as they became more similar to one another in their production of words, while the other ten did not. Furthermore, we found higher resting state functional connectivity between the vmPFC and right temporoparietal junction (rTPJ) for the ten individuals in dyads who converged compared to those who did not converge. This provides complementary evidence for the importance of the vmPFC and rTPJ for conversational synchrony in healthy individuals and suggests that intrinsic neural network activity is related to individual differences in conversational synchrony.

Apolipoprotein E ε4 Specifically Modulates the Hippocampus Functional Connectivity Network in Patients With Amnestic Mild Cognitive Impairment

The presence of both apolipoprotein E (APOE) ε4 allele and amnestic mild cognitive impairment (aMCI) are considered to be risk factors for Alzheimer’s disease (AD). Numerous neuroimaging studies have suggested that the modulation of APOE ε4 affects intrinsic functional brain networks, both in healthy populations and in AD patients. However, it remains largely unclear whether and how ε4 allele modulates the brain’s functional network architecture in subjects with aMCI. Using resting-state functional magnetic resonance imaging (fMRI) and graph-theory approaches-functional connectivity strength (FCS), we investigate the topological organization of the whole-brain functional network in 28 aMCI ε4 carriers and 38 aMCI ε3ε3 carriers. In the present study, we first observe that ε4-related FCS increases in the right hippocampus/parahippocampal gyrus (HIP/PHG). Subsequent seed-based resting-state functional connectivity (RSFC) analysis revealed that, compared with the ε3ε3 carriers, the ε4 carriers had lower or higher RSFCs between the right HIP/PHG seed and the bilateral medial prefrontal cortex (MPFC) or the occipital cortex, respectively. Further correlation analyses have revealed that the FCS values in the right HIP/PHG and lower HIP/PHG-RSFCs with the bilateral MPFC were significantly correlated with the impairment of episodic memory and executive function in the aMCI ε4 carriers. Importantly, the logistic regression analysis showed that the HIP/PHG-RSFC with the bilateral MPFC predicted aMCI-conversion to AD. These findings suggest that the APOE ε4 allele may modulate the large-scale brain network in aMCI subjects, facilitating our understanding of how the entire assembly of the brain network reorganizes in response to APOE variants in aMCI. Further longitudinal studies need to be conducted, in order to examine whether these network measures could serve as primary predictors of conversion from aMCI ε4 carriers to AD.

Habenular connectivity may predict treatment response in depressed psychiatric inpatients

IntroductionThe habenula (Hb) is a small midbrain structure that signals negative events and may play a major role in the etiology of psychiatric disorders including depression. The lateral Hb has three major efferent connections: serotonergic raphe nuclei, noradrenergic locus coeruleus, and dopaminergic ventral tegmental area/substantia nigra compacta. We wanted to test whether Hb connectivity may be important to predict treatment outcomes in depression patients. MethodsWe studied whether habenular connectivity at admission into a psychiatric clinic can predict treatment response. We used an inpatient sample (N = 175) to assess habenular connectivity (diffusion tensor imaging and resting state functional connectivity (RSFC) between the Hb and its targets) close to admission. In addition, we obtained the Patient Health Questionnaire-depression module (PHQ-9) close to admission and at discharge. Inpatients in the study entered the clinic with at least moderately severe depression (score 15 and up). Inpatients considered treatment resistant had scores of 9 or more at discharge. ResultsCompared to responders, treatment non-responders had lower fractional anisotropy in the right Hb afferent fibers and lower RSFC between right Hb and median raphe, but higher RSFC between left Hb and locus coeruleus. A logistic regression model was significantly different from chance, and explained 27.7% of the variance in treatment resistance (sensitivity = 75%; specificity = 71.9%). DiscussionThe anatomical and functional connectivity of the Hb may be a predictor of treatment success in psychiatric populations. Limitations include the Hb small size and the limited time (5 min) of resting state data obtained.

An Inverse U-Shaped Curve of Resting-State Networks in Individuals at High Risk of Alzheimer's Disease.

Higher functional connectivity (FC) in resting-state networks has been shown in individuals at risk of Alzheimer's disease (AD) by many studies. However, the longitudinal trajectories of the FC remain unknown. The present 35-month follow-up study aimed to explore longitudinal changes in higher FC in multiple resting-state networks in subjects with the apolipoprotein E ε4 allele (ApoE4) and/or amnestic mild cognitive impairment (aMCI). Fifty-one subjects with aMCI and 64 cognitively normal (CN) subjects underwent neuropsychological tests and resting-state functional magnetic resonance imaging (fMRI) scans twice from April 2011 to June 2015. Subjects were divided into 4 groups according to diagnosis and ApoE4 status. The CN non-ApoE4 group served as a control group, and other groups served as AD risk groups. The cross-sectional and longitudinal patterns of multiple resting-state networks, including default mode network, hippocampus network, executive control network, and salience network, were explored by comparing FC data between groups and between time points, respectively. At baseline, compared with the control group, the AD risk groups showed higher FC with 8 regions in multiple networks. At follow-up, 6 of the regions displayed longitudinally decreased FC in AD risk groups. In contrast, the FC with all of these regions was maintained in the control group. Notably, among the 3 risk groups, most of the higher FC at baseline (5 of the 8 regions) and longitudinally decreased FC at follow-up (4 of the 6 regions) were shown in the aMCI ApoE4 group. Higher resting-state FC is followed by a decline in subjects at AD risk, and this inverse U-shaped trajectory is more notable in subjects with higher risk.

Structural connectivity-defined thalamic subregions have different functional connectivity abnormalities in multiple sclerosis patients: Implications for clinical correlations.

In spite of the well-known importance of thalami in multiple sclerosis (MS), only limited data on whole and subregional thalamic functional connectivity (FC) changes are available. Using diffusion tensor imaging, we performed a structural connectivity based thalamic parcellation and investigated subregional thalamic resting-state (RS) FC alterations and their relationship with clinical/cognitive measures in MS. MRI data from a reference set of healthy controls (HC) were used to parcellate the thalami into five subregions, according to their structural connectivity. For each thalamic subregion, a seed-based RS FC analysis was performed in 187 MS patients and 94 HC. Correlations between thalamic RS FC and clinical/cognitive variables were assessed. Compared to HC, MS patients showed increased intra- and inter-thalamic RS FC for almost all thalamic subregions, and increased RS FC between all thalamic subregions and the left insula. Frontal and motor thalamic subregions also showed reduced RS FC with the caudate nucleus. For the temporal thalamic subregion, we observed reduced RS FC with the ipsilateral thalamus, anterior and middle cingulate cortex, and cerebellum. Compared to cognitively preserved, cognitively impaired MS patients had higher thalamic RS FC with several temporal areas. In MS patients, lower RS FC between thalamic subregions and the caudate and cingulate cortex correlated with worse motor performance, whereas higher RS FC with the insula correlated with better motor performance. The main thalamic subregions have different RS-FC abnormalities in MS patients. Increased thalamic RS FC with the insula may have a compensatory role, whereas increased RS FC with temporal areas, observed in patients with cognitive impairment may reflect maladaptive mechanisms. Hum Brain Mapp 38:6005-6018, 2017. © 2017 Wiley Periodicals, Inc.

Left Frontal Hub Connectivity during Memory Performance Supports Reserve in Aging and Mild Cognitive Impairment.

Reserve in aging and Alzheimer’s disease (AD) is defined as maintaining cognition at a relatively high level in the presence of neurodegeneration, an ability often associated with higher education among other life factors. Recent evidence suggests that higher resting-state functional connectivity within the frontoparietal control network, specifically the left frontal cortex (LFC) hub, contributes to higher reserve. Following up these previous resting-state fMRI findings, we probed memory-task related functional connectivity of the LFC hub as a neural substrate of reserve. In elderly controls (CN, n = 37) and patients with mild cognitive impairment (MCI, n = 17), we assessed global connectivity of the LFC hub during successful face-name association learning, using generalized psychophysiological interaction analyses. Reserve was quantified as residualized memory performance, accounted for gender and proxies of neurodegeneration (age, hippocampus atrophy, and APOE genotype). We found that greater education was associated with higher LFC-connectivity in both CN and MCI during successful memory. Furthermore, higher LFC-connectivity predicted higher residualized memory (i.e., reserve). These results suggest that higher LFC-connectivity contributes to reserve in both healthy and pathological aging.

L-Dopa responsiveness is associated with distinctive connectivity patterns in advanced Parkinson's disease.

Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to l-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3 × 3 × 2.5 mm3 voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an l-dopa challenge. False discovery rate-corrected P was set at < 0.05 for a 2-tailed t test. A greater improvement in UPDRS-III scores following l-dopa administration was characterized by higher resting-state functional connectivity between the prefrontal cortex and the striatum (P = 0.001) and lower resting-state functional connectivity between the pallidum (P = 0.001), subthalamic nucleus (P = 0.003), and the paracentral lobule (supplementary motor area, mesial primary motor, and primary sensory areas). Our findings show characteristic basal ganglia resting-state functional connectivity patterns associated with different degrees of l-dopa responsiveness in patients with advanced Parkinson's disease. l-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response. © 2017 International Parkinson and Movement Disorder Society.

Impact of Resveratrol on Glucose Control, Hippocampal Structure and Connectivity, and Memory Performance in Patients with Mild Cognitive Impairment.

In healthy older adults, resveratrol supplementation has been shown to improve long-term glucose control, resting-state functional connectivity (RSFC) of the hippocampus, and memory function. Here, we aimed to investigate if these beneficial effects extend to individuals at high-risk for dementia, i.e., patients with mild cognitive impairment (MCI). In a randomized, double-blind interventional study, 40 well-characterized patients with MCI (21 females; 50–80 years) completed 26 weeks of resveratrol (200 mg/d; n = 18) or placebo (1,015 mg/d olive oil; n = 22) intake. Serum levels of glucose, glycated hemoglobin A1c and insulin were determined before and after intervention. Moreover, cerebral magnetic resonance imaging (MRI) (3T) (n = 14 vs. 16) was conducted to analyze hippocampus volume, microstructure and RSFC, and neuropsychological testing was conducted to assess learning and memory (primary endpoint) at both time points. In comparison to the control group, resveratrol supplementation resulted in lower glycated hemoglobin A1c concentration with a moderate effect size (ANOVARM p = 0.059, Cohen's d = 0.66), higher RSFC between right anterior hippocampus and right angular cortex (p < 0.001), and led to a moderate preservation of left anterior hippocampus volume (ANOVARM p = 0.061, Cohen's d = 0.68). No significant differences in memory performance emerged between groups. This proof-of-concept study indicates for the first-time that resveratrol intake may reduce glycated hemoglobin A1c, preserves hippocampus volume, and improves hippocampus RSFC in at-risk patients for dementia. Larger trials with longer intervention time should now determine if these benefits can be validated and extended to cognitive function.

The effect of single-dose methylphenidate on resting-state network functional connectivity in ADHD.

We examined the effect of a single dose of methylphenidate (MPH) on whole brain functional connectivity, assessed using resting state functional MRI (rsfMRI), in young people with ADHD. 16 young people with ADHD participated in two rsfMRI scans in a randomized, placebo-controlled study with an acute dose of MPH (20mg). 15 typically developing controls also performed the task under placebo conditions. The network-based statistic (NBS) was used to identify differential connectivity patterns between the MPH and placebo conditions in the ADHD group. Mean connectivity of the resulting sub-network was examined in the ADHD and control groups. Resting state functional connectivity (RSFC) analysis revealed significantly reduced connectivity under MPH compared to placebo in young people with ADHD. Findings were robust across a range of thresholds. No sub-networks of increased connectivity were found at any threshold. Mean connectivity of the identified sub-network was significantly higher in ADHD individuals in the placebo condition compared to controls, however there was no difference between MPH condition and controls. We demonstrated a significant MPH-related reduction in RSFC in a large, robust network primarily involving occipital, temporal and cerebellar regions, and visual, executive and default mode networks. These findings suggest that MPH is 'normalising' a higher RSFC in young people with ADHD. This study is a novel addition to the understanding of treatment effects on the brain in ADHD.

EP 6. Longitudinal resting state functional connectivity patterns in the early phase of recovery from Aphasia in temporoparietal stroke

Background Poststroke aphasia recovery evolves in space and time. Substantial language improvements can be observed within the first days after stroke. However, underlying changes in the functional status of the language network during the acute phase remain to be demonstrated. Methods In a resting-state functional connectivity (RSFC) fMRI study we assessed changes in functional connectivity repeatedly (acute( t 1) = 2 ± 1, subacute( t 2) = 10 ± 2 days post-onset) in aphasic patients ( N = 12, 62 ± 14 years, 10 male) with left temporoparietal stroke. Language comprehension and production scores were calculated based on the Aachener Aphasie-Test. For RSFC analysis 9mm spherical ROIs reflecting core language regions in the left anterior inferior frontal (aIFG: x = −54 y = 32 z = 1, MNI-space), posterior middle temporal gyrus (pMTG: x = −54 y = −43 z = 4) and their right hemisphere homologous were selected. Results Seed-to-whole-brain analysis from left aIFG or pMTG revealed RSFC to right hemisphere homologous frontal or temporal areas at t 1 and t 2 ( p > .05, FWE corrected). Longitudinally, RSFC from left pMTG to left aIFG as well as RSFC from left aIFG to left frontal (operculum, insula, premotor cortex) and to right frontal (IFG, premotor cortex) areas increased significantly from t 1 to t 2 ( p > .001, uncorrected). Subsequent ROI-to-ROI analysis revealed increased RSFC between left aIFG and pMTG from t 1 to t 2 associated with improved language production ( r = .579, p = .049). During the acute phase ( t 1) better scores for language comprehension and production were predicted by higher RSFC between left aIFG and right aIFG ( r = .736 p = .006). Conclusion We observed early ipsi- and contralesional changes in the language network’s functional connectivity and associated language improvements indicative of acute diaschisis and subsequent reorganization within the distributed language network.