Posterior Default Mode Network Research Articles

Modeling EEG Signals From the Bottom Up

The default mode network (DMN) is deactivated by stimulation. We aimed to assess the DMN reactivity impairment by routine EEG recordings in stroke patients with impaired consciousness.Binocular light flashes were delivered at 1 Hz in 1-minute epochs, following a 1-minute baseline (PRE). The EEG was decomposed in a series of binary oscillatory macrostates by topographic spectral clustering. The most deactivated macrostate was labeled the default EEG macrostate (DEM). Its reactivity (DER) was quantified as the decrease in DEM occurrence probability during stimulation. A normalized DER index (DERI) was calculated as DER/PRE. The measures were compared between 14 healthy controls and 32 comatose patients under EEG monitoring following an acute stroke.The DEM was mapped to the posterior DMN hubs. In the patients, these DEM source dipoles were 3–4 times less frequent and were associated with an increased theta activity. Even in a reduced 6-channel montage, a DER below 6.26% corresponding to a DERI below 0.25 could discriminate the patients with sensitivity and specificity well above 80%.The method detected the DMN impairment in post-stroke coma patients.The DEM and its reactivity to stimulation could be useful to monitor the DMN function at bedside.

Altered White Matter Tracts in the Somatosensory, Salience, Motor, and Default Mode Networks in 7-Year-Old Children Living with Human Immunodeficiency Virus: A Tractographic Analysis.

Introduction: Even with the increased access and early initiation of combination antiretroviral therapy, children with perinatally acquired human immunodeficiency virus (CPHIV) continue to demonstrate white matter alterations. Children perinatally HIV-exposed, but uninfected (CHEU) alike show differences in white matter integrity compared with children who are HIV-unexposed and uninfected (CHUU). Objectives: Mapping white matter connections that link gray matter regions that form resting-state (RS) functional networks may demonstrate whether structural and functional connectivity alterations in HIV infection and exposure may be related. We hypothesized reduced structural connectivity in CPHIV within the default mode network (DMN), visual, ventral DMN (vDMN), somatosensory, salience, auditory, motor, executive, basal ganglia, and posterior DMN (pDMN). We also hypothesized that CHEU will have increased structural connectivity compared with CHUU in the vDMN, somatosensory, pDMN, dorsal attention, salience, auditory, motor and basal ganglia. Methods: Study participants were 61 seven-year-old CPHIV and 46 age-matched children who are HIV uninfected (CHU) (19 CHEU). We used diffusion tensor imaging-based tractography to investigate white matter connections that link gray matter regions within RS functional networks. Results: We found altered white matter integrity in the somatosensory, salience, default mode, and motor networks of CPHIV compared with CHU. The superior temporal cortex, superior frontal cortex, and putamen were affected in all four networks and have also been reported to demonstrate morphological alterations in the same cohort. In CHEU, white matter integrity was higher in the visual network, pDMN, and motor network compared with CHUU. Conclusion: Our results suggest that altered white matter integrity may influence gray matter morphology and functional network alterations. Impact statement The long-term effects of human immunodeficiency virus (HIV) and exposure on the developing brain in the combination antiretroviral therapy era are still not well known. We use diffusion tensor imaging-based tractography to explore these effects on white matter connections that link gray matter regions within functional networks. Our findings provide a context for HIV-associated white matter and connectivity abnormalities.

Development of functional connectivity within and among the resting-state networks in anesthetized rhesus monkeys

ObjectiveThe age-related changes in the resting-state networks (RSNs) exhibited temporally specific patterns in humans, and humans and rhesus monkeys have similar RSNs. We hypothesized that the RSNs in rhesus monkeys experienced similar developmental patterns as humans. MethodsWe acquired resting-state fMRI data from 62 rhesus monkeys, which were divided into childhood, adolescence, and early adulthood groups. Group independent component analysis (ICA) was used to identify monkey RSNs. We detected the between-group differences in the RSNs and static, dynamic, and effective functional network connections (FNCs) using one-way variance analysis (ANOVA) and post-hoc analysis. ResultsEight rhesus RSNs were identified, including cerebellum (CN), left and right lateral visual (LVN and RVN), posterior default mode (pDMN), visuospatial (VSN), frontal (FN), salience (SN), and sensorimotor networks (SMN). In internal connections, the CN, SN, FN, and SMN mainly matured in early adulthood. The static FNCs associated with FN, SN, pDMN primarily experienced fast descending slow ascending type (U-shaped) developmental patterns for maturation, and the dynamic FNCs related to pDMN (RVN, CN, and SMN) and SMN (CN) were mature in early adulthood. The effective FNC results showed that the pDMN and VSN (stimulated), SN (inhibited), and FN (first inhibited then stimulated) chiefly matured in early adulthood. ConclusionWe identified eight monkey RSNs, which exhibited similar development patterns as humans. All the RSNs and FNCs in monkeys were not widely changed but fine-tuned. Our study clarified that the progressive synchronization, exploration, and regulation of cognitive RSNs within the pDMN, FN, SN, and VSN denoted potential maturation of the RSNs throughout development. We confirmed the development patterns of RSNs and FNCs would support the use of monkeys as a best animal model for human brain function.

Brain Functional Changes in Stroke Following Rehabilitation Using Brain-Computer Interface-Assisted Motor Imagery With and Without tDCS: A Pilot Study.

Brain-computer interface-assisted motor imagery (MI-BCI) or transcranial direct current stimulation (tDCS) has been proven effective in post-stroke motor function enhancement, yet whether the combination of MI-BCI and tDCS may further benefit the rehabilitation of motor functions remains unknown. This study investigated brain functional activity and connectivity changes after a 2 week MI-BCI and tDCS combined intervention in 19 chronic subcortical stroke patients. Patients were randomized into MI-BCI with tDCS group and MI-BCI only group who underwent 10 sessions of 20 min real or sham tDCS followed by 1 h MI-BCI training with robotic feedback. We derived amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and functional connectivity (FC) from resting-state functional magnetic resonance imaging (fMRI) data pre- and post-intervention. At baseline, stroke patients had lower ALFF in the ipsilesional somatomotor network (SMN), lower ReHo in the contralesional insula, and higher ALFF/Reho in the bilateral posterior default mode network (DMN) compared to age-matched healthy controls. After the intervention, the MI-BCI only group showed increased ALFF in contralesional SMN and decreased ALFF/Reho in the posterior DMN. In contrast, no post-intervention changes were detected in the MI-BCI + tDCS group. Furthermore, higher increases in ALFF/ReHo/FC measures were related to better motor function recovery (measured by the Fugl-Meyer Assessment scores) in the MI-BCI group while the opposite association was detected in the MI-BCI + tDCS group. Taken together, our findings suggest that brain functional re-normalization and network-specific compensation were found in the MI-BCI only group but not in the MI-BCI + tDCS group although both groups gained significant motor function improvement post-intervention with no group difference. MI-BCI and tDCS may exert differential or even opposing impact on brain functional reorganization during post-stroke motor rehabilitation; therefore, the integration of the two strategies requires further refinement to improve efficacy and effectiveness.

Resting state functional networks in 1-to-3-year-old typically developing children

Brain functional networks undergo substantial development and refinement during the first years of life. Yet, the maturational pathways of functional network development remain poorly understood. Using resting-state fMRI data acquired during natural sleep from 24 typically developing toddlers, ages 1.5–3.5 years, we aimed to examine the large-scale resting-state functional networks and their relationship with age and developmental skills. Specifically, two network organization indices reflecting network connectivity and spatial variability were derived. Our results revealed that reduced spatial variability or increased network homogeneity in one of the default mode network components was associated with age, with older children displaying less spatially variable posterior DMN subcomponent, consistent with the notion of increased spatial and functional specialization. Further, greater network homogeneity in higher-order functional networks, including the posterior default mode, salience, and language networks, was associated with more advanced developmental skills measured with a standardized assessment of early learning, regardless of age. These results not only improve our understanding of brain functional network development during toddler years, but also inform the relationship between brain network organization and emerging cognitive and behavioral skills.

Obese Individuals Show Disrupted Dynamic Functional Connectivity between Basal Ganglia and Salience Networks.

Previous functional magnetic resonance imaging (fMRI) studies have showed obesity (OB)-related alterations in intrinsic functional connectivity (FC) within and between different resting-state networks (RSNs). However, few studies have examined dynamic functional connectivity (DFC). Thus, we employed resting-state fMRI with independent component analysis (ICA) and DFC analysis to investigate the alterations in FC within and between RSNs in 56 individuals with OB and 46 normal-weight (NW) controls. ICA identified six RSNs, including basal ganglia (BG), salience network (SN), right executive control network/left executive control network, and anterior default-mode network (aDMN)/posterior default-mode network. The DFC analysis identified four FC states. OB compared with NW had more occurrences and a longer mean dwell time (MDT) in state 2 (positive connectivity of BG with other RSN) and also had higher FC of BG-SN in other states. Body mass index was positively correlated with MDT and FCs of BG-aDMN (state 2) and BG-SN (state 4). DFC analysis within more refined nodes of RSNs showed that OB had more occurrences and a longer MDT in state 1 in which caudate had positive connections with the other network nodes. The findings suggest an association between caudate-related and BG-related positive FC in OB, which was not revealed by traditional FC analysis, highlighting the utility of adding DFC to the more conventional methods.

Pretreatment intranetwork connectivity can predict the outcomes in idiopathic tinnitus patients treated with sound therapy.

Previous studies demonstrated that brain morphological differences and distinct patterns of neural activation exist in tinnitus patients with different prognoses after sound therapy. This study aimed to explore possible differences in intrinsic network‐level functional connectivity (FC) in patients with different outcomes after sound therapy (narrow band noise). We examined intrinsic FC using resting‐state functional magnetic resonance imaging in 78 idiopathic tinnitus patients (including 35 effectively treated and 43 ineffectively treated) and 52 healthy controls (HCs) via independent component analysis. We also investigated the associations between the differences in FC and clinical variables. Analyses revealed significantly altered intranetwork connectivity in the auditory network (AUN) and some nonauditory‐related networks in the EG/IG patients compared to HCs; compared with EG patients, IG patients showed decreased intranetwork connectivity in the anterior default mode network (aDMN) and AUN. Meanwhile, robust differences were also evident in internetwork connectivity between some nonauditory‐related networks (salience network and executive control network; posterior default mode network and dorsal attention network) in the EG relative to IG patients. We combined intranetwork connectivity in the aDMN and AUN as an imaging indicator to evaluate patient outcomes and screen patients before treatment; this approach reached a sensitivity of 94.3% and a specificity of 76.7%. Our study suggests that tinnitus patients with different outcomes show distinct network‐level functional reorganization patterns. Intranetwork connectivity in the aDMN and AUN may be indicators that can be used to predict prognoses in patients with idiopathic tinnitus and screen patients before sound therapy.

Polarity-specific high-definition transcranial direct current stimulation of the anterior and posterior default mode network improves remote memory retrieval

BackgroundPrevious studies show that activity in the posterior default mode network (pDMN), including the posterior cingulate cortex and the precuneus, is correlated with the success of long-term episodic memory retrieval. However, the role of the anterior DMN (aDMN) including the medial prefrontal cortex is still unclear. Some studies show that activating the medial prefrontal cortex improves memory retrieval while other studies show deactivation of the medial prefrontal cortex in successful retrieval of episodic memories, suggesting a possible functional dissociation between the aDMN and pDMN. ObjectiveIn the current study, we aim to causally explore this probable dissociation using high-definition transcranial direct current stimulation (HD-tDCS). MethodsWe perform a randomised double-blinded two-visit placebo-controlled study with 84 healthy young adults. During Visit 1 they learn 75 Swahili-English word-associations. Seven days later, they randomly receive either anodal, cathodal or sham HD-tDCS targeting the pDMN or aDMN while they recall what they have previously learned. ResultsWe demonstrate that anodal stimulation of the pDMN and cathodal stimulation of the aDMN, equally improve the percentage of Swahili-English word-associations recalled 7 days after learning. ConclusionsModulating the activity in the aDMN and pDMN causally affect memory retrieval performance. HD-tDCS of the aDMN and pDMN shows that anodal stimulation of the pDMN and cathodal stimulation of the aDMN increases memory retrieval performance one week after the learning phase. Given consistent evidence, it is highly likely that we are increasing the activity in the pDMN with anodal pDMN stimulation. However, it is not clear if cathodal HD-tDCS targetting aDMN works via decoupling from the pDMN or via indirectly disinhibit pDMN.

Default mode network dissociation linking cerebral beta amyloid retention and depression in cognitively normal older adults.

Cerebral beta amyloid (Aβ) deposition and late-life depression (LLD) are known to be associated with the trajectory of Alzheimer's disease (AD). However, their neurobiological link is not clear. Previous studies showed aberrant functional connectivity (FC) changes in the default mode network (DMN) in early Aβ deposition and LLD, but its mediating role has not been elucidated. This study was performed to investigate the distinctive association pattern of DMN FC linking LLD and Aβ retention in cognitively normal older adults. A total of 235 cognitively normal older adults with (n = 118) and without depression (n = 117) underwent resting-state functional magnetic resonance imaging and 18F-flutemetamol positron emission tomography to investigate the associations between Aβ burden, depression, and DMN FC. Independent component analysis showed increased anterior DMN FC and decreased posterior DMN FC in the depression group compared with the no depression group. Global cerebral Aβ retention was positively correlated with anterior and negatively correlated with posterior DMN FC. Anterior DMN FC was positively correlated with severity of depression, whereas posterior DMN FC was negatively correlated with cognitive function. In addition, the effects of global cerebral Aβ retention on severity of depression were mediated by subgenual anterior cingulate FC. Our results of anterior and posterior DMN FC dissociation pattern may be pivotal in linking cerebral Aβ pathology and LLD in the course of AD progression. Further longitudinal studies are needed to confirm the causal relationships between cerebral Aβ retention and LLD.

Dementia with Lewy bodies: association of Alzheimer pathology with functional connectivity networks.

Dementia with Lewy bodies (DLB) is neuropathologically defined by the presence of α-synuclein aggregates, but many DLB cases show concurrent Alzheimer’s disease pathology in the form of amyloid-β plaques and tau neurofibrillary tangles.The first objective of this study was to investigate the effect of Alzheimer’s disease co-pathology on functional network changes within the default mode network (DMN) in DLB. Second, we studied how the distribution of tau pathology measured with PET relates to functional connectivity in DLB. Twenty-seven DLB, 26 Alzheimer’s disease and 99 cognitively unimpaired participants (balanced on age and sex to the DLB group) underwent tau-PET with AV-1451 (flortaucipir), amyloid-β-PET with Pittsburgh compound-B (PiB) and resting-state functional MRI scans. The resing-state functional MRI data were used to assess functional connectivity within the posterior DMN. This was then correlated with overall cortical flortaucipir PET and PiB PET standardized uptake value ratio (SUVr). The strength of interregional functional connectivity was assessed using the Schaefer atlas. Tau-PET covariance was measured as the correlation in flortaucipir SUVr between any two regions across participants. The association between region-to-region functional connectivity and tau-PET covariance was assessed using linear regression. Additionally, we identified the region with highest and the region with lowest tau SUVrs (tau hot- and cold spots) and tested whether tau SUVr in all other brain regions was associated with the strength of functional connectivity to these tau hot and cold spots.A reduction in posterior DMN connectivity correlated with overall higher cortical tau- (r = −0.39, P = 0.04) and amyloid-PET uptake (r = −0.41, P = 0.03) in the DLB group, i.e. patients with DLB who have more concurrent Alzheimer’s disease pathology showed a more severe loss of DMN connectivity. Higher functional connectivity between regions was associated with higher tau covariance in cognitively unimpaired, Alzheimer’s disease and DLB. Furthermore, higher functional connectivity of a target region to the tau hotspot (i.e. inferior/medial temporal cortex) was related to higher flortaucipir SUVrs in the target region, whereas higher functional connectivity to the tau cold spot (i.e. sensory-motor cortex) was related to lower flortaucipir SUVr in the target region.Our findings suggest that a higher burden of Alzheimer’s disease co-pathology in patients with DLB is associated with more Alzheimer’s disease-like changes in functional connectivity. Furthermore, we found an association between the brain’s functional network architecture and the distribution of tau pathology that has recently been described in Alzheimer’s disease. We show that this relationship also exists in patients with DLB, indicating that similar mechanisms of connectivity-dependent occurrence of tau pathology might be at work in both diseases.

Functional Connectivity between Task-Positive Networks and the Left Precuneus as a Biomarker of Response to Lamotrigine in Bipolar Depression: A Pilot Study.

Treatment of bipolar depression poses a significant clinical challenge. Lamotrigine is one of a few efficacious drugs, however, it needs to be titrated very slowly and response can only be assessed after 10–12 weeks. With only a proportion of patients responding, an exploration of factors underlying treatment responsivity is of paramount clinical importance, as it may lead to an allocation of the drug to those most likely to respond to it. This study aimed at identifying differences in patterns of pre-treatment resting state functional connectivity (rsFC) that may underlie response to lamotrigine in bipolar depression. After a baseline MRI scan, twenty-one patients with bipolar depression were treated with lamotrigine in an open-label design; response, defined as ≥50% decrease in Hamilton Depression Rating Scale (HAMD) score, was assessed after 10–12 weeks of treatment. Twenty healthy controls had a baseline clinical assessment and scan but did not receive any treatment. Fifteen out of 21 (71%) patients responded to lamotrigine. Treatment responsivity was associated with enhanced pre-treatment rsFC of the right fronto-parietal network (FPN) and dorsal attention network (DAN) with left precuneus. The lack of treatment response was additionally characterised by reduced rsFC: of the DAN with right middle temporal gyrus; of the default mode network (DMN) with left precuneus; of the extended sensory-motor area with areas including the left hippocampus/left amygdala and left subcallosal cortex/nucleus accumbens; and of the left FPN with left inferior temporal gyrus/occipital fusiform gyrus/lateral occipital cortex. The results suggest that preserved rsFC between the FPN and DAN, the networks involved in cognitive control, and the hub of the posterior DMN, the left precuneus, may be critical for good response to lamotrigine as an add-on treatment in patients with bipolar depression. The study also suggests a more general decrease in rsFC to be related to poor treatment responsivity.

Functional MRI Shows Altered Deactivation and a Corresponding Decrease in Functional Connectivity of the Default Mode Network in Patients with Gliomas

The default mode network normally decreases in activity during externally directed tasks. Although default mode network connectivity is disrupted in numerous brain pathologies, default mode network deactivation has not been studied in patients with brain tumors. We investigated default mode network deactivation with language task-based fMRI by measuring the anticorrelation of a critical default mode network node, the posterior cingulate cortex, in patients with gliomas and controls; furthermore, we examined default mode network functional connectivity in these patients with task-based and resting-state fMRI. In 10 healthy controls and 30 patients with gliomas, the posterior cingulate cortex was identified on task-based fMRI and was used as an ROI to create connectivity maps from task-based and resting-state fMRI data. We compared the average correlation in each default mode network region between patients and controls for each correlation map and stratified patients by tumor location, hemisphere, and grade. Patients with gliomas (P = .001) and, in particular, patients with tumors near the posterior default mode network (P < .001) showed less posterior cingulate cortex anticorrelation in task-based fMRI than controls. Patients with both left- and right-hemisphere tumors, as well as those with grade IV tumors, showed significantly lower posterior cingulate cortex anticorrelation than controls (P = .02, .03, and <.001, respectively). Functional connectivity in each default mode network region was not significantly different between task-based and resting-state maps. Task-based fMRI showed impaired deactivation of the default mode network in patients with gliomas. The functional connectivity of the default mode network in both task-based and resting-state fMRI in patients with gliomas using the posterior cingulate cortex identified in task-based fMRI as an ROI for seed-based correlation analysis has strong overlap.

Antiepileptic Efficacy and Network Connectivity Modulation of Repetitive Transcranial Magnetic Stimulation by Vertex Suppression.

A core feature of drug-resistant epilepsy is hyperexcitability in the motor cortex, and low-frequency repetitive transcranial magnetic stimulation (rTMS) is a suitable treatment for seizures. However, the antiepileptic effect causing network reorganization has rarely been studied. Here, we assessed the impact of rTMS on functional network connectivity (FNC) in resting functional networks (RSNs) and their relation to treatment response. Fourteen patients with medically intractable epilepsy received inhibitive rTMS with a figure-of-eight coil over the vertex for 10 days spread across two weeks. We designed a 6-week follow-up phase divided into four time points to investigate FNC and rTMS-induced timing-dependent plasticity, such as seizure frequency and abnormal interictal discharges on electroencephalography (EEG). For psychiatric comorbidities, the Hamilton Depression Scale (HAM-D) and the Hamilton Anxiety Scale (HAM-A) were applied to measure depression and anxiety before and after rTMS. FNC was also compared to that of a cohort of 17 healthy control subjects. The after-effects of rTMS included all subjects that achieved the significant decrease rate of more than 50% in interictal epileptiform discharges and seizure frequency, 12 (14) patients with the reduction rate above 50% compared to the baseline, as well as emotional improvements in depression and anxiety (p < 0.05). In the analysis of RSNs, we found a higher synchronization between the sensorimotor network (SMN) and posterior default-mode network (pDMN) in epileptic patients than in healthy controls. In contrast to pre-rTMS, the results demonstrated a weaker FNC between the anterior DMN (aDMN) and SMN after rTMS, while the FNC between the aDMN and dorsal attention network (DAN) was greater (p < 0.05, FDR corrected). Importantly, the depressive score was anticorrelated with the FNC of the aDMN-SMN (r = −0.67, p = 0.0022), which was markedly different in the good and bad response groups treated with rTMS (p = 0.0115). Based on the vertex suppression by rTMS, it is possible to achieve temporary clinical efficacy by modulating network reorganization in the DMN and SMN for patients with refractory epilepsy.

Potential Alterations of Functional Connectivity Analysis in the Patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common diseases in urology, but its pathogenesis remains unclear. As a kind of chronic pain which the patients suffered for more than 3 months, we investigated the influence on patients' brain functional connectivity in resting state. Methods We recruited a cohort of 18 right-handed male patients with CP/CPPS and 21 healthy male right-handed age-matched controls. Their resting-state fMRI data and structural MRI data were preprocessed and processed by RESTPlus V1.22. To assess the integrity of the default mode network (DMN), we utilized the voxel-wised analysis that we set medial prefrontal cortex (mPFC) and posterior cingulate gyrus (PCC) as seed points to compare the global functional connectivity (FC) strength. Results Compared with healthy control, the FC strength between left mPFC and posterior DMN decreased in the group of CP/CPPS (P < 0.05, GFR correction, voxel P < 0.01, cluster P < 0.05), and the FC strength between the left anterior cerebellar lobe and posterior DMN increased (P < 0.05, GFR correction, voxel P < 0.01, cluster P < 0.05). In the patient group, there was a positive correlation between the increased FC strength and the score of the Hospital Anxiety and Depression Scale (HADS) anxiety subscale (r = 0.5509, P = 0.0178) in the left anterior cerebellar lobe, a negative correlation between the decreased FC strength and the score of the National Institutes of Health Chronic Prostatitis Symptom Index (r = −0.6281, P = 0.0053) in the area of left mPFC, and a negative correlation between the decreased FC strength and the score of HADS anxiety subscale (r = −0.5252, P = 0.0252). Conclusion Patients with CP/CPPS had alterations in brain function, which consisted of the default mode network's compromised integrity. These alterations might play a crucial role in the pathogenesis and development of CP/CPPS.

Cortical morphological study in cerebral small vessel disease patients with subcortical ischemic depression

Objective: To explore the characteristics of cortical morphology in cerebral small vessel disease (CSVD) patients with subcortical ischemic depression (SID) and its relationship with clinical symptoms. Methods: A total of 88 patients with CSVD in the First Affiliated Hospital of Anhui Medical University were enrolled from July 2017 to July 2020. The subjects were divided into CSVD-non depression group (CSVD-ND, n=58) and SID group (n=30) according to the geriatric depression scale (GDS). The 3D-T1 MRI images were obtained from all subjects. The computed anatomy toolbox 12 (CAT 12) was used for image processing and cortical segmentation to obtain the cortical thickness (CTh) and surface metrics, including gyrification index (GI), sulcus depth (SD) and fractal dimension (FD). A comparison at the vertex- and region-of-interest (ROI)-wise levels were performed by the general linear model, and correlation analysis were conducted between cortical morphometric measurements and GDS scores. Finally, mean CTh (mCTh) was extracted for binary logistic regression analysis. Results: At the vertex-wise level, compared with the CSVD-ND group, the SID patients showed increased CTh in clusters mainly located in the posterior default mode network (pDMN), such as the precuneus(Pcu), the superior parietal gyrus (SPG) and the right postcentral gyrus (PoCG). As for the surface measurements, the GI value and the FD value were increased in clusters of Pcu and inferior temporal gyrus (ITG), respectively, in the SID group. ROIs analyses showed that apart from the Pcu, the SPG and the right PoCG, CTh alterations in the SID group were involved in a wider range of regions, extending to the right precentral gyrus ((2.27±0.20) cm3 vs (2.12±0.26) cm3, P=0.007), the left paracentral gyrus ((2.18±0.20) cm3 vs (2.05±0.23) cm3, P=0.008) and so on, than that in the CSVD-ND group.Compared with the CSVD-ND patients, the SID patients showed increased GI in the right PoCG ((25.31±1.11) vs (24.23±1.27), P<0.05). Correlation analysis showed that CTh in the right Pcu was positively correlated with the GDS scores (r=0.4, P<0.05). Further binary logistic regression analysis showed that in comparison with the subjects in the reference group (<2.367 cm3), the odds ratio(95%CI) for SID patients in the highest tertile of mCTh (>2.473 cm3) were 6.373 (1.254-32.389) after multivariable adjustment (sex, age, years of education, total intracranial volume, traditional imaging findings of CSVD, cognitive function (CAMCOG-C) and mCTh). Conclusion: Both CTh and cortical complexity were increased in CSVD patients with SID, especially in the clusters of pDMN, and CTh may be an important risk factor for SID.

Movement, mood and cognition: Preliminary insight into the effects of electroconvulsive therapy in depression through a data-driven resting-state connectivity analysis

IntroductionECT is an effective treatment for depression. Beyond its therapeutic effect on mood it has a unique impact on psychomotor and cognitive symptoms.Its mechanism of action remains still unclear. To investigate this, we set out to study the brain’s response to ECT from a large-scale brain-network perspective.ObjectivesThe aim of this study was to investigate changes in resting-state functional connectivity following ECT at the whole brain, between-network and within-network level, in patients with a depressive episode.MethodsResting-state FMRI data were collected from 17 patients with depression before and after an ECT course. Using a group independent component analysis approach, we focused on four networks that are known to be affected in depression: the salience network (SN), default mode network (DMN), cognitive executive network (CEN) and a subcortical network (SCN). Clinical measures including mood, cognition and psychomotor symptoms were assessed.ResultsECT increased connectivity of the left CEN with the left angular gyrus and left middle frontal gyrus. An increase in left CEN within network connectivity was observed. Both the right CEN and the SCN showed increased connectivity with the precuneus. Furthermore, the anterior DMN showed increased connectivity with the left amygdala. Finally, improvement of psychomotor retardation was positively correlated with an increase of within-posterior DMN connectivity.ConclusionsWe demonstrate that ECT induces a significant increase of connectivity at both the whole brain and within-network level. Furthermore, we provide first evidence on the association between an increase of within posterior DMN connectivity and an improvement of psychomotor retardation, a core symptom of depression.DisclosureNo significant relationships.

Brain Structural and Functional Reorganization in Tinnitus Patients Without Hearing Loss After Sound Therapy: A Preliminary Longitudinal Study.

Sound therapy is one of the most common first-line treatments for idiopathic tinnitus. We aimed to investigate the brain structural and functional alterations between patients with idiopathic tinnitus without hearing loss (HL) and healthy controls (HCs) and between patients before and after sound therapy (narrow band noise). Structural and resting-state functional images were acquired from 13 tinnitus patients without HL and 18 HCs before and after 6 months of narrow band sound therapy (only patients received the treatment). Voxel-based morphometry (VBM) and independent component analysis (ICA) were conducted to separately investigate the brain structural and functional changes. Associations between brain changes and clinical variables were also performed. After the treatment, the % improvement of THI score was −1.30% (± 63.40%). Compared with HCs, tinnitus patients showed gray matter and white matter atrophy in the left middle temporal gyrus at baseline, and the gray matter volume was further reduced after the treatment. The patients also showed increased white matter volume in the cingulum (cingulate), right calcarine, left rolandic operculum, and left parietal and frontal lobes. Additionally, compared with HCs, tinnitus patients exhibited positive [medial visual network (mVN) and sensorimotor network (SMN), mVN and auditory network (AN)] and negative [mVN and lateral visual network (lVN)] internetwork functional connectivity (FC) at baseline and negative [left frontoparietal network (LFPN) and dorsal attention network (DAN), AN and posterior default mode network (pDMN)] internetwork FC after the narrow band sound therapy. The patients also showed negative [LFPN and right frontoparietal network (RFPN), LFPN and RFPN, anterior default mode network (aDMN) and AN, aDMN and DAN] internetwork FC after the treatment when compared with baseline. Our findings suggest that although the outcomes of idiopathic tinnitus patients without HL were not very good when the improvement of THI scores was used as an evaluation indicator, the patients experienced significant differences in auditory-related and non-auditory-related brain reorganization before and after the narrow band sound therapy, that is, sound therapy may have a significant effect on brain reorganization in patients with idiopathic tinnitus. This study may provide some new useful information for the understanding of mechanisms underlying idiopathic tinnitus.

Increased Within-Network Functional Connectivity May Predict NEDA Status in Fingolimod-Treated MS Patients.

Only a few studies have evaluated the brain functional changes associated with disease-modifying therapies (DMTs) in multiple sclerosis (MS), though none used a composite measure of clinical and MRI outcomes to evaluate DMT-related brain functional connectivity (FC) measures predictive of short-term outcome. Therefore, we investigated the following: (1) baseline FC differences between patients who showed evidence of disease activity after a specific DMT and those who did not; (2) DMT-related effects on FC, and; (3) possible relationships between DMT-related FC changes and changes in performance. We used a previously analyzed dataset of 30 relapsing MS patients who underwent fingolimod treatment for 6 months and applied the “no evidence of disease activity” (NEDA-3) status as a clinical response indicator of treatment efficacy. Resting-state fMRI data were analyzed to obtain within- and between-network FC measures. After therapy, 14 patients achieved NEDA-3 status (hereinafter NEDA), while 16 did not (EDA). The two groups significantly differed at baseline, with the NEDA group having higher within-network FC in the anterior and posterior default mode, auditory, orbitofrontal, and right frontoparietal networks than the EDA. After therapy, NEDA showed significantly reduced within-network FC in the posterior default mode and left frontoparietal networks and increased between-network FC in the posterior default mode/orbitofrontal networks; they also showed PASAT improvement, which was correlated with greater within-network FC decrease in the posterior default mode network and with greater between-network FC increase. No significant longitudinal FC changes were found in the EDA. Taken together, these findings suggest that NEDA status after fingolimod is related to higher within-network FC at baseline and to a consistent functional reorganization after therapy.

Neuroimaging Markers of Mal de Débarquement Syndrome.

Mal de débarquement syndrome (MdDS) is a motion-induced disorder of oscillating vertigo that persists after the motion has ceased. The neuroimaging characteristics of the MdDS brain state have been investigated with studies on brain metabolism, structure, functional connectivity, and measurements of synchronicity. Baseline metabolism and resting-state functional connectivity studies indicate that a limbic focus in the left entorhinal cortex and amygdala may be important in the pathology of MdDS, as these structures are hypermetabolic in MdDS and exhibit increased functional connectivity to posterior sensory processing areas and reduced connectivity to the frontal and temporal cortices. Both structures are tunable with periodic stimulation, with neurons in the entorhinal cortex required for spatial navigation, acting as a critical efferent pathway to the hippocampus, and sending and receiving projections from much of the neocortex. Voxel-based morphometry measurements have revealed volume differences between MdDS and healthy controls in hubs of multiple resting-state networks including the default mode, salience, and executive control networks. In particular, volume in the bilateral anterior cingulate cortices decreases and volume in the bilateral inferior frontal gyri/anterior insulas increases with longer duration of illness. Paired with noninvasive neuromodulation interventions, functional neuroimaging with functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and simultaneous fMRI-EEG have shown changes in resting-state functional connectivity that correlate with symptom modulation, particularly in the posterior default mode network. Reduced parieto-occipital connectivity with the entorhinal cortex and reduced long-range fronto-parieto-occipital connectivity correlate with symptom improvement. Though there is a general theme of desynchronization correlating with reduced MdDS symptoms, the prediction of optimal stimulation parameters for noninvasive brain stimulation in individuals with MdDS remains a challenge due to the large parameter space. However, the pairing of functional neuroimaging and noninvasive brain stimulation can serve as a probe into the biological underpinnings of MdDS and iteratively lead to optimal parameter space identification.

Functional MRI Correlates of Sleep Quality in HIV.

ObjectiveTo examine resting-state functional MRI (rs-fMRI) networks related to sleep in the context of HIV infection.Methodsrs-fMRI data were collected in 40 HIV-infected (HIV+) individuals at baseline (treatment-naive), 12 week (post-treatment) and one year timepoints. A group of 50 age-matched HIV-negative (HIV-) individuals were also imaged at baseline and one year timepoints. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered at all timepoints. Using group independent component analysis (ICA), maps of functional networks were generated from fMRI data; from these, sleep-related networks were selected. A generalized linear model (GLM) was used to analyze if these networks were significantly associated with the PSQI score, and if this relationship was influenced by HIV status/treatment or timepoint.ResultsHIV+ individuals had significantly lower PSQI score after treatment (p=0.022). Networks extracted from group ICA analysis included the anterior and posterior default mode network (DMN), central executive network (CEN), bilateral frontoparietal networks (FPNs), and the anterior cingulate cortex salience network (ACC SN). We found the posterior DMN, right FPN, and ACC SN GLMs showed significantly higher goodness-of-fit after incorporating PSQI data (p = 0.0204, 0.044, 0.044, respectively). Furthermore, the correlation between ACC SN and posterior DMN connectivity was significantly decreased in the HIV+ cohort.ConclusionFunctional networks such as the DMN, FPN, CEN, and ACC SN are altered in poor sleep, as measured by the PSQI score. Furthermore, the relationship between these networks and PSQI is different in the HIV+ and HIV- populations.