Reduced Default Mode Network Connectivity Research Articles

Neuroimaging correlates of Alzheimer's disease biomarker concentrations in a racially diverse high-risk cohort of middle-aged adults.

In this study, we investigated biomarkers in a midlife, racially diverse, at-risk cohort to facilitate early identification and intervention. We examined neuroimaging measures, including resting state functional magnetic resonance imaging (fMRI), white matter hyperintensity vo (WMH), and hippocampal volumes, alongside cerebrospinal fluid (CSF) markers. Our data set included 76 cognitively unimpaired, middle-aged, Black Americans (N=29, F/M=17/12) and Non-Hispanic White (N=47, F/M=27/20) individuals. We compared cerebrospinal fluid phosphorylated tau141 and amyloid beta (Aβ)42 to fMRI default mode network (DMN) subnetwork connectivity, WMH volumes, and hippocampal volumes. Results revealed a significant race × Aβ42 interaction in Black Americans: lower Aβ42 was associated with reduced DMN connectivity and increased WMH volumes regions but not in non-Hispanic White individuals. Our findings suggest that precuneus DMN connectivity and temporal WMHs may be linked to Alzheimer's disease risk pathology during middle age, particularly in Black Americans. Cerebrospinal fluid (CSF) amyloid beta (Aβ)42 relates to precuneus functional connectivity in Black, but not White, Americans. Higher white matter hyperintensity volume relates to lower CSF Aβ42 in Black Americans. Precuneus may be a hub for early Alzheimer's disease pathology changes detected by functional connectivity.

Functional connectivity changes in meditators and novices during yoga nidra practice

Yoga nidra (YN) practice aims to induce a deeply relaxed state akin to sleep while maintaining heightened awareness. Despite the growing interest in its clinical applications, a comprehensive understanding of the underlying neural correlates of the practice of YN remains largely unexplored. In this fMRI investigation, we aim to discover the differences between wakeful resting states and states attained during YN practice. The study included individuals experienced in meditation and/or yogic practices, referred to as ‘meditators’ (n = 30), and novice controls (n = 31). The GLM analysis, based on audio instructions, demonstrated activation related to auditory cues without concurrent default mode network (DMN) deactivation. DMN seed based functional connectivity (FC) analysis revealed significant reductions in connectivity among meditators during YN as compared to controls. We did not find differences between the two groups during the pre and post resting state scans. Moreover, when DMN-FC was compared between the YN state and resting state, meditators showed distinct decoupling, whereas controls showed increased DMN-FC. Finally, participants exhibit a remarkable correlation between reduced DMN connectivity during YN and self-reported hours of cumulative meditation and yoga practice. Together, these results suggest a unique neural modulation of the DMN in meditators during YN which results in being restful yet aware, aligned with their subjective experience of the practice. The study deepens our understanding of the neural mechanisms of YN, revealing distinct DMN connectivity decoupling in meditators and its relationship with meditation and yoga experience. These findings have interdisciplinary implications for neuroscience, psychology, and yogic disciplines.

Default mode network connectivity and social dysfunction in children with Attention Deficit/Hyperactivity Disorder

ObjectiveAttention Deficit/Hyperactivity Disorder (ADHD) negatively affects social functioning; however, its neurological underpinnings remain unclear. Altered Default Mode Network (DMN) connectivity may contribute to social dysfunction in ADHD. We investigated whether DMN's dynamic functional connectivity (dFC) alterations were associated with social dysfunction in individuals with ADHD. MethodsResting-state fMRI was used to examine DMN subsystems (dorsal medial prefrontal cortex (dMPFC), medial temporal lobe (MTL)) and the midline core in 40 male ADHD patients (7-10 years) and 45 healthy controls (HCs). Connectivity correlations with symptoms and demographic data were assessed. Group-based analyses compared rsFC between groups with two-sample t-tests and post-hoc analyses. ResultsSocial dysfunction in ADHD patients was related to reduced DMN connectivity, specifically in the MTL subsystem and the midline core. ADHD patients showed decreased dFC between parahippocampal cortex (PHC) and left superior frontal gyrus, and between ventral medial prefrontal cortex (vMPFC) and right middle frontal gyrus compared to HCs (MTL subsystem). Additionally, decreased dFC between posterior cingulate cortex (PCC), anterior medial prefrontal cortex (aMPFC), and right angular gyrus (midline core) was observed in ADHD patients relative to HCs. No abnormal connectivity was found within the dMPFC. ConclusionPreliminary findings suggest that DMN connectional abnormalities may contribute to social dysfunction in ADHD, providing insights into the disorder's neurobiology and pathophysiology.

Applying Functional Imaging to Clinical Practice: Are We Making Progress Toward Its Promise?

Applying Functional Imaging to Clinical Practice: Are We Making Progress Toward Its Promise?

Evidence for Schizophrenia-Specific Pathophysiology of Nicotine Dependence.

Tobacco use is the top preventable cause of early mortality in schizophrenia. Over 60% of people with schizophrenia smoke, three times the general prevalence. The biological basis of this increased risk is not understood, and existing interventions do not target schizophrenia-specific pathology. We therefore used a connectome-wide analysis to identify schizophrenia-specific circuits of nicotine addiction. We reanalyzed data from two studies: In Cohort 1, 35 smokers (18 schizophrenia, 17 control) underwent resting-state fMRI and clinical characterization. A multivariate pattern analysis of whole-connectome data was used to identify the strongest links between cigarette use and functional connectivity. In Cohort 2, 12 schizophrenia participants and 12 controls were enrolled in a randomized, controlled crossover study of nicotine patch with resting-state fMRI. We correlated change in network functional connectivity with nicotine dose. In Cohort 1, the strongest (p < 0.001) correlate between connectivity and cigarette use was driven by individual variation in default mode network (DMN) topography. In individuals with greater daily cigarette consumption, we observed a pathological expansion of the DMN territory into the identified parieto-occipital region, while in individuals with lower daily cigarette consumption, this region was external to the DMN. This effect was entirely driven by schizophrenia participants. Given the relationship between DMN topography and nicotine use we observed in Cohort 1, we sought to directly test the impact of nicotine on this network using an independent second cohort. In Cohort 2, nicotine reduced DMN connectivity in a dose-dependent manner (R = −0.50; 95% CI −0.75 to −0.12, p < 0.05). In the placebo condition, schizophrenia subjects had hyperconnectivity compared to controls (p < 0.05). Nicotine administration normalized DMN hyperconnectivity in schizophrenia. We here provide direct evidence that the biological basis of nicotine dependence is different in schizophrenia and in non-schizophrenia populations. Our results suggest the high prevalence of nicotine use in schizophrenia may be an attempt to correct a network deficit known to interfere with cognition.

Aberrant default mode connectivity in adolescents with early-onset psychosis: A resting state fMRI study

Abnormal default mode network (DMN) connectivity has been found in schizophrenia and other psychotic disorders. However, there are limited studies on early onset psychosis (EOP), and their results show lack of agreement. Here, we investigated within-network DMN connectivity in EOP compared to healthy controls (HC), and its relationship to clinical characteristics.A sample of 68 adolescent patients with EOP (mean age 16.53 ± 1.12 [SD] years, females 66%) and 95 HC (mean age 16.24 ± 1.50 [SD], females 60%) from two Scandinavian cohorts underwent resting state functional magnetic resonance imaging (rsfMRI). A group independent component analysis (ICA) was performed to identify the DMN across all participants. Dual regression was used to estimate spatial maps reflecting each participant’s DMN network, which were compared between EOP and HC using voxel-wise general linear models and permutation-based analyses. Subgroup analyses were performed within the patient group, to explore associations between diagnostic subcategories and current use of psychotropic medication in relation to connectivity strength.The analysis revealed significantly reduced DMN connectivity in EOP compared to HC in the posterior cingulate cortex, precuneus, fusiform cortex, putamen, pallidum, amygdala, and insula. The subgroup analysis in the EOP group showed strongest deviations for affective psychosis, followed by other psychotic disorders and schizophrenia. There was no association between DMN connectivity strength and the current use of psychotropic medication.In conclusion, the findings demonstrate weaker DMN connectivity in adolescent patients with EOP compared to healthy peers, and differential effects across diagnostic subcategories, which may inform our understanding of underlying disease mechanisms in EOP.

Reduced default mode network connectivity relative to white matter integrity is associated with poor cognitive outcomes in patients with idiopathic normal pressure hydrocephalus

BackgroundThe aim of this study was to investigate whether default mode network (DMN) connectivity and brain white matter integrity at baseline were associated with severe cognitive impairments at baseline and poor cognitive outcomes after shunt placement in patients with idiopathic normal pressure hydrocephalus (iNPH).MethodsTwenty consecutive patients with iNPH whose symptoms were followed for 6 months after shunt placement and 10 healthy controls (HCs) were enrolled. DMN connectivity and brain white matter integrity at baseline in the patients with iNPH and HCs were detected by using resting-state functional magnetic resonance imaging (MRI) with independent component analysis and diffusion tensor imaging, respectively, and these MRI indexes were compared between the patients with iNPH and HCs. Performance on neuropsychological tests for memory and executive function and on the gait test was assessed in the patients with iNPH at baseline and 6 months after shunt placement. We divided the patients with iNPH into the relatively preserved and reduced DMN connectivity groups using the MRI indexes for DMN connectivity and brain white matter integrity, and the clinical measures were compared between the relatively preserved and reduced DMN connectivity groups.ResultsMean DMN connectivity in the iNPH group was significantly lower than that in the HC group and was significantly positively correlated with Rey auditory verbal learning test (RAVLT) immediate recall scores and frontal assessment battery (FAB) scores. Mean fractional anisotropy of the whole-brain white matter skeleton in the iNPH group was significantly lower than that in the HC group. The reduced DMN connectivity group showed significantly worse performance on the RAVLT at baseline and significantly worse improvement in the RAVLT immediate recall and recognition scores and the FAB scores than the preserved DMN connectivity group. Moreover, the RAVLT recognition score highly discriminated patients with relatively preserved DMN connectivity from those with relatively reduced DMN connectivity.ConclusionsOur findings indicated that iNPH patients with reduced DMN connectivity relative to the severity of brain white matter disruption have severe memory deficits at baseline and poorer cognitive outcomes after shunt placement. However, further larger-scale studies are needed to confirm these findings.

Association between the Onset of Idiopathic Normal Pressure Hydrocephalus Symptoms and Reduced Default Mode Network Connectivity

Objective: The aim was to examine the association between connectivity changes in the default mode network (DMN) and the progression of idiopathic normal pressure hydrocephalus (iNPH). Methods: We retrospectively recruited cases of preclinical and clinical iNPH from 2,196 patients who had received whole-body ¹⁸F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scanning. We included 31 cases with asymptomatic ventriculomegaly with features of iNPH on MRI (AVIM; reported as preclinical iNPH) and 12 with iNPH. We performed a voxel-based analysis of the brain FDG-PET images of the AVIM and iNPH groups as well as for each background-matched normal control (NC) group, using Statistical Parametric Mapping 12. Volume of interest (VOI)-based analysis was also performed. We set the VOI as the region from the precuneus to the posterior cingulate cortices (PCC), and compared the mean regional standardized uptake value ratio (SUVR) between the AVIM and iNPH group FDG-PET/CT images and each corresponding NC group. Results: The voxel-based analysis showed a greater decreased FDG uptake in the PCC in the iNPH group than in the AVIM group. The VOI-based analysis revealed no significant difference in the mean SUVR of the AVIM group and the corresponding NC group, but that of the iNPH group was significantly lower than that of its corresponding NC group. Conclusions: DMN connectivity was reduced in the clinical iNPH group but not in the preclinical group. These data suggest that alterations in the functional connectivity of the DMN are related to the onset of iNPH symptoms.

Callous-unemotional traits and reduced default mode network connectivity within a community sample of children.

Callous-unemotional (CU) traits characterize a subset of youth at risk for persistent and serious antisocial behavior. Differences in resting state connectivity in the default mode network (DMN) have been associated with CU traits in forensic and clinical samples of adolescents and with deficient interpersonal/affective traits (often operationalized as Factor 1 psychopathy traits) in adults. It is unclear whether these brain-behavior associations extend to community-based children. Using mixed model analyses, we tested the associations between CU traits and within-network resting-state connectivity of seven task-activated networks and the DMN using data from 9,636 9-11-year-olds in the Adolescent Brain Cognitive Development (ABCD) study. Even after accounting for comorbid externalizing problems, higher levels of CU traits were associated with reduced connectivity within the DMN. This finding is consistent with prior literature surrounding psychopathy and CU traits in clinically and forensically based populations, suggesting the correlation likely exists on a spectrum, can be detected in childhood, and is not restricted to children with significant antisocial behavior.

Modulation of respiration pattern variability and its relation to anxiety symptoms in remitted recurrent depression

BackgroundDepression is related to default mode network (DMN) connectivity and higher respiration pattern variability (RPV). In addition, DMN connectivity and RPV are interrelated and predict a poorer clinical course of depression. The association of RPV and depression might further be boosted by anxiety levels. Aim of the present study was to investigate whether a mindfulness-based training in emotionally challenged remitted depressed participants (rMDD) leads to reduced DMN connectivity and lower RPV, and if RPV interacts with anxiety levels. MethodsTo challenge participants, sad mood was induced with keywords of personal negative life events in 49 rMDD during fMRI before and after a 4-week mindfulness-based attention training (MBAT) or progressive muscle relaxation. Respiration was measured by means of a built-in respiration belt. ResultsAfter both trainings, rMDD showed no significant changes in DMN connectivity. However, MBAT was effective in reducing the RPV which was related to lower anxiety levels especially in high anxious individuals. ConclusionsRPV can be influenced by training which may hint to an underlying biological pathway of training effects. Importantly, these effects seem to be associated with anxiety levels. Therefore, respiration focused training might be an important tool assisting the treatment of depression and anxiety.

Chronic Early Stress Impairs Default Mode Network Connectivity in Preadolescents and Their Mothers

BackgroundEarly life stress (ELS) bears long-term negative consequences throughout life. Yet ELS effect is mostly unknown, and no study has followed children to test its impact on the default mode network (DMN) in relation to maternal behavior across childhood. Focusing on brain oscillations, we utilized a unique cohort of war-exposed preadolescent children (11–13 years of age) and their mothers followed from early childhood to examine the effects of ELS combined with observed parenting on DMN connectivity and power in mother and child. MethodsParticipants included 161 mothers and children (children: 39 exposed/36 control subjects; mothers: 44 exposed/42 control subjects) who underwent magnetoencephalography scanning during rest. ResultsStress exposure reduced DMN connectivity in mother and child; however, in mothers, the impaired connectivity occurred in the alpha band, whereas among children it occurred in the theta band, a biomarker of the developing brain. Maternal anxiety, depression, and posttraumatic symptoms in early childhood predicted lower maternal DMN connectivity. Among children, the experience of intrusive, anxious, and uncontained parenting across the first decade and greater cortisol production in late childhood predicted reduced DMN connectivity in preadolescence. Impairments to theta DMN connectivity increased in children with posttraumatic stress disorder. ConclusionsFindings indicate that ELS disrupts the synchronous coordination of distinct brain areas into coherent functioning of the DMN network, a core network implicated in self-relevant processes. Results suggest that one pathway for the lifelong effects of ELS on psychopathology and physical illness relate to impaired coherence of the DMN and its role in maintaining quiescence, alternating internal and external attention, and supporting the sense of self.

Altered resting-state connectivity within default mode network associated with late chronotype

Current evidence suggests late chronotype individuals have an increased risk of developing depression. However, the underlying neural mechanisms of this association are not fully understood. Forty-six healthy, right-handed individuals free of current or previous diagnosis of depression, family history of depression or sleep disorder underwent resting-state functional Magnetic Resonance Imaging (rsFMRI). Using an Independent Component Analysis (ICA) approach, the Default Mode Network (DMN) was identified based on a well validated template. Linear effects of chronotype on DMN connectivity were tested for significance using non-parametric permutation tests (applying 5000 permutations). Sleep quality, age, gender, measures of mood and anxiety, time of scan and cortical grey matter volume were included as covariates in the regression model. A significant positive correlation between chronotype and functional connectivity within nodes of the DMN was observed, including; bilateral PCC and precuneus, such that later chronotype (participants with lower rMEQ scores) was associated with decreased connectivity within these regions. The current results appear consistent with altered DMN connectivity in depressed patients and weighted evidence towards reduced DMN connectivity in other at-risk populations which may, in part, explain the increased vulnerability for depression in late chronotype individuals. The effect may be driven by self-critical thoughts associated with late chronotype although future studies are needed to directly investigate this.

Posttraumatic stress disorder symptom severity is associated with reduced default mode network connectivity in individuals with elevated genetic risk for psychopathology

Accumulating evidence suggests that posttraumatic stress disorder (PTSD) is associated with disrupted default mode network (DMN) connectivity, but findings across studies have not been uniform. Individual differences in relevant genes may account for some of the reported variability in the relationship between DMN connectivity and PTSD. In this study, we investigated this possibility using genome-wide association study (GWAS) derived polygenic risk scores (PRSs) for relevant psychiatric traits. We hypothesized that the association between PTSD and DMN connectivity would be moderated by genetic risk for one or more psychiatric traits such that individuals with elevated polygenic risk for psychopathology and severe PTSD would exhibit disrupted DMN connectivity. Participants were 156 white, non-Hispanic veterans of the wars in Iraq and Afghanistan who were genotyped and underwent resting state functional magnetic resonance imaging and clinical assessment. PRSs for neuroticism, anxiety, major depressive disorder, and cross-disorder risk (based on five psychiatric disorders) were calculated using summary statistics from published large-scale consortia-based GWASs. Cross-disorder polygenic risk influenced the relationship between DMN connectivity and PTSD symptom severity such that individuals at greater genetic risk showed a significant negative association between PTSD symptom severity and connectivity between the posterior cingulate cortex and right middle temporal gyrus. Polygenic risk for neuroticism, anxiety, and major depressive disorder did not influence DMN connectivity directly or through an interaction with PTSD. Findings illustrate the potential power of genome-wide PRSs to advance understanding of the relationship between PTSD and DMN connectivity, a putative neural endophenotype of the disorder.

5-HT2A Gene Variants Moderate the Association between PTSD and Reduced Default Mode Network Connectivity.

The default mode network (DMN) has been used to study disruptions of functional connectivity in a wide variety of psychiatric and neurological conditions, including posttraumatic stress disorder (PTSD). Studies indicate that the serotonin system exerts a modulatory influence on DMN connectivity; however, no prior study has examined associations between serotonin receptor gene variants and DMN connectivity in either clinical or healthy samples. We examined serotonin receptor single nucleotide polymorphisms (SNPs), PTSD, and their interactions for association with DMN connectivity in 134 White non-Hispanic veterans. We began by analyzing candidate SNPs identified in prior meta-analyses of relevant psychiatric traits and found that rs7997012 (an HTR2A SNP), implicated previously in anti-depressant medication response in the Sequenced Treatment Alternatives for Depression study (STAR*D; McMahon et al., 2006), interacted with PTSD to predict reduced connectivity between the posterior cingulate cortex (PCC) and the right medial prefrontal cortex and right middle temporal gyrus (MTG). rs130058 (HTR1B) was associated with connectivity between the PCC and right angular gyrus. We then expanded our analysis to 99 HTR1B and HTR2A SNPs and found two HTR2A SNPs (rs977003 and rs7322347) that significantly moderated the association between PTSD severity and the PCC-right MTG component of the DMN after correcting for multiple testing. Finally, to obtain a more precise localization of the most significant SNP × PTSD interaction, we performed a whole cortex vertex-wise analysis of the rs977003 effect. This analysis revealed the locus of the pre-frontal effect to be in portions of the superior frontal gyrus, while the temporal lobe effect was centered in the middle and inferior temporal gyri. These findings point to the influence of HTR2A variants on DMN connectivity and advance knowledge of the role of 5-HT2A receptors in the neurobiology of PTSD.

Reduced default mode network connectivity following combat trauma

Recent studies show decreased functional connectivity in the default mode network (DMN) in PTSD; however, few have directly examined combat trauma specifically. There is limited understanding of how combat itself may affect the DMN. Some literature suggests that trauma exposure, rather than PTSD, can disrupt the DMN. To further elucidate the effect of trauma and PTSD on the DMN, we investigated DMN functional connectivity during the resting-state in veterans with PTSD, combat-exposed controls, and never-traumatized healthy controls. Results revealed that DMN connectivity was reduced in veterans exposed to combat trauma with and without PTSD compared to healthy civilian controls. Specifically, both groups of veterans demonstrated weaker connectivity within a network involving the precuneus, medial prefrontal cortex (mPFC) and right superior parietal lobule regardless of whether the mPFC or precuneus was chosen as a seed region. Findings suggest that the experience of trauma, rather than the pathology of PTSD, may be related to DMN changes.

Using a temporal decomposition technique to investigate dynamic changes in subnetworks derived from resting state fMRI during generalized spike-and-wave discharges: an EEG-fMRI pilot study

Event Abstract Back to Event Using a temporal decomposition technique to investigate dynamic changes in subnetworks derived from resting state fMRI during generalized spike-and-wave discharges: an EEG-fMRI pilot study Chayanin Tangwiriyasakul1*, Suejen Perani1, Siti N. Yaakub1 and Mark P. Richardson1 1 King's College London, Basic and Clinical Neuroscience, United Kingdom Introduction: Many recent studies suggest that generalized seizures arise from abnormality in whole brain networks (Richardson et al. 2012). Most evidence shows abnormalities in static networks (e.g. reduced default mode network connectivity). In this study, we are interested to investigate dynamic changes in the level of synchrony during generalized spike and wave discharge (GSW) period using simultaneous EEG-fMRI recordings. Methods: Three patients with newly diagnosed epilepsy underwent four resting state scans (each scan lasts ~10 minutes). Pre-processed fMRI data were band-pass filtered between 0.04-0.07 Hz (Glerean et al. 2011) and a Hilbert transform was applied. The AAL atlas was used to divide the brain into 90 cortical regions, with each region represented by the first principal component of the instantaneous phase of all voxels in the region. We estimated a binary synchronization matrix at each time-point with regions considered to be synchronized if the phase difference was less than π/6, giving 296 binary synchronization matrices for each subject (Ponce-Alvarez et al. 2014). Tensor decomposition technique was then used to extract sub-networks, resulting in 9 major components (90x90 matrices). GSW periods were marked by an experienced neurologist. Results: A total of 32 GSW occurrences were found in this study. Figure 1 shows an example of temporal evolution of nine subnetworks in patient-1. From visual inspection (see Figure 1B/1C), 20 out of 32 SWD occurrences (63%) were found during a minimum of network synchrony (or turning point, labelled as T in Fig 1B/C). One the other hand, 9 events (27%) were found while the net contribution from all subnetworks was in a maximum stable-and-synchronous state (or plateau state, labelled as P in Fig 1B/C). The remaining 3 GSW occurrences (10%) were unclassified. Figure 1: Subnetwork structure of spatiotemporal synchronization patterns in patient-1. A) The 9 detected subnetworks. B) Temporal activation strength of each subnetwork. C) Total activation strength of all nine subnetworks (which represents a level of total network synchrony). D) Temporal evolution of phase difference throughout the ~10 minute scan. E) Band-pass filtered fMRI raw signals in 25 brain regions. The red stripes indicate the period during GSW. Note that T = turning and P = Plateau. Conclusion: Up to now, the mechanism underlying seizure generation is not yet clear. The results from this study may suggest two possible causes of SWD generations: (1) transition between two states, which may cause instability in the brain networks or (2) over synchronization of the brain networks. In the future, a larger study population is needed to address these two hypotheses. Figure 1

Default mode network connectivity in patients with idiopathic normal pressure hydrocephalus

Idiopathic normal pressure hydrocephalus (iNPH) is a neurological disorder characterized by gait disturbance, cognitive impairment, and incontinence. It is unclear whether the pathophysiology of iNPH is associated with alterations in the default mode network (DMN). The authors investigated alterations in the DMN of patients with iNPH and sought to determine whether a relationship exists between the resting-state functional connectivity of the DMN and a patient's clinical symptoms. Resting-state functional MRI (rs-fMRI) was performed in 16 preoperative patients with iNPH and 15 neurologically healthy control subjects of a similar age. Independent component and dual-regression analyses were used to quantify DMN connectivity. The patients' clinical symptoms were rated according to the iNPH grading scale (iNPHGS). Each of their specific clinical symptoms were rated according to the cognitive, gait, and urinary continence domains of iNPHGS, and neurocognitive status was assessed using the Mini-Mental State Examination, Frontal Assessment Battery (FAB), and Trail Making Test Part A. The strength of DMN connectivity was compared between patients and controls, and the correlation between DMN connectivity and iNPHGS was examined using both region of interest (ROI)-based analysis and voxel-based analysis. The correlation between DMN connectivity and each of the specific clinical symptoms, as well as neurocognitive status, was examined using voxel-based analysis. Both ROI-based and voxel-based analyses revealed reduced DMN connectivity in patients with iNPH. ROI-based analysis showed increased DMN connectivity with worsening clinical symptoms of iNPH. Consistently, voxel-based analyses revealed that DMN connectivity correlated positively with the iNPHGS score, as well as the cognitive and urinary continence domain scores, and negatively with the FAB score. The significant peak in correlation in each case was localized to the precuneus. This is the first study to establish alterations in the DMN of patients with iNPH. DMN connectivity may be a useful indicator of the severity of clinical symptoms in patients with iNPH.

Reduced default mode network connectivity in schizophrenia patients

In the present study, we explored possible alterations in the default mode network (DMN) and its functional connectivity in 41 schizophrenia patients and 42 age-matched healthy controls. Schizophrenia patients displayed reduced activation in the ventromedial prefrontal cortex, left superior temporal gyrus including auditory cortex and temporal pole. Psychophysiological interaction analysis revealed reduced connectivity between left superior temporal gyrus including auditory cortex and the left temporal pole in schizophrenia patients compared to healthy subjects.

Reduced default mode network connectivity in treatment‐resistant idiopathic generalized epilepsy

Idiopathic generalized epilepsy (IGE) resistant to treatment is common, but its neuronal correlates are not entirely understood. Therefore, the aim of this study was to examine resting-state default mode network (DMN) functional connectivity in patients with treatment-resistant IGE. Treatment resistance was defined as continuing seizures despite an adequate dose of valproic acid (valproate, VPA). Data from 60 epilepsy patients and 38 healthy controls who underwent simultaneous electroencephalography (EEG) and resting-state functional magnetic resonance imaging (fMRI) were included (EEG/fMRI). Independent component analysis (ICA) and dual regression were used to quantify DMN connectivity. Confirmatory analysis using seed-based voxel correlation was performed. There was a significant reduction of DMN connectivity in patients with treatment-resistant epilepsy when compared to patients who were treatment responsive and healthy controls. Connectivity was negatively correlated with duration of epilepsy. Our findings in this large sample of patients with IGE indicate the presence of reduced DMN connectivity in IGE and show that connectivity is further reduced in treatment-resistant epilepsy. DMN connectivity may be useful as a biomarker for treatment resistance.

1716 – Abnormal resting-state functional connectivity in euthymic bipolar patients

Bipolar disorders (BD) are characterized by emotional and cognitive impairment reflected in functional MRI studies. Although the default mode network (DMN) would be also impaired, resting-state activity was much less explored in these patients. Our current study aims to assess the DMN functional connectivity in euthymic bipolar patients (EBP) in order to identify potential trait abnormalities of this disease. Fifteen EBP and 15 matched healthy controls (HC) underwent fMRI exam during 6 min resting state (rest while keeping attention focused on a visual cross on a projection screen). The Independent Component Analysis (ICA) was used to identify DMN network and functional connectivity in each subject. The DMN group maps of EBP and of HS were compared statistically. Additionally, within-group analysis was performed in EBP group to explore the effect of disease duration on functional connectivity. Compared to HC, EBP showed reduced DMN connectivity within medial prefrontal cortex, right angular gyrus and left occipital lobe as well as abnormal recruitment of right insula and right middle cingulate gyrus. For the EBP group, significant positive correlation between disease duration and functional connectivity has been observed within left amygdala and right middle cingulate cortex. Our results revealed decreased DMN functional connectivity within frontal and parietal regions in EBP and suggest abnormal internally-focused activity in these patients. Furthermore, the abnormal recruitment of limbic regions such as right insula, middle cingulate gyrus and amygdala may reflect emotional instability and hyperreactivity of EBP, which might be amplified with the disease evolution.