Decreased Default Mode Network Connectivity Research Articles

Hearing loss is associated with decreased default-mode network connectivity in individuals with mild cognitive impairment

Mild cognitive impairment (MCI) and hearing loss (HL) have been separately associated with increased dementia risk. These highly co-occurring dementia risk factors are associated with aberrant functional brain connectivity. In individuals with HL aberrant functional connectivity has been associated with cognitive impairment. In individuals with MCI, aberrant brain connectivity has been associated with severity of cognitive impairment and conversion to dementia. Despite the high prevalence of HL in individuals with MCI, the relationship between the two is understudied, especially in the context of functional connectivity. Participantsinclude 94 older adults with MCI. Hearing measures include pure-tone hearing thresholds and speech-reception thresholds. In analyses with pure-tone hearing loss, participants were classified as having normal hearing (n = 60) or hearing loss (n = 34) based on a pure-tone screening protocol. We used independent component analyses on resting-state functional magnetic resonance imaging data to identify the default-mode network (DMN). Analysis of variance with covariate control was used to investigate DMN connectivity differences between the normally hearing individuals with MCI and individuals with MCI and pure-tone HL. A linear regression was used to investigate the relationship between speech-reception threshold and DMN connectivity in the whole sample.Compared to those with MCI and normal hearing, those with MCI and pure-tone HL had decreased connectivity between the DMN and the caudate and thalamus. There was no difference in DMN connectivity as a function of speech-reception threshold.Our findings indicate that in individuals with MCI, HL is associated with decreased connectivity between the DMN and regions important for sensory and cognitive processing. This suggests that the increased risk for cognitive decline and dementia in individuals with HL may be due to decreased DMN connectivity in individuals with HL.

Aberrant Intrinsic Brain Network Functional Connectivity During a Face-Matching Task in Women Diagnosed With Premenstrual Dysphoric Disorder

BackgroundPremenstrual dysphoric disorder (PMDD) is characterized by affective, cognitive, and physical symptoms, suggesting alterations at the brain network level. Women with PMDD demonstrate aberrant discrimination of facial emotions during the luteal phase of the menstrual cycle and altered reactivity to emotional stimuli. However, previous studies assessing emotional task-related brain reactivity using region-of-interest or whole-brain analysis have reported conflicting findings. Therefore, we utilized both region-of-interest task-reactivity and seed-voxel functional connectivity (FC) approaches to test for differences in the default mode network, salience network, and central executive network between women with PMDD and control participants during an emotional-processing task that yields an optimal setup for investigating brain network changes in PMDD. MethodsTwenty-four women with PMDD and 27 control participants were classified according to the Daily Record of Severity of Problems. Participants underwent functional magnetic resonance imaging scans while completing the emotional face-matching task during the midfollicular and late-luteal phases of their menstrual cycle. ResultsNo significant between-group differences in brain reactivity were found using region-of-interest analysis. In the FC analysis, a main effect of diagnosis was found showing decreased default mode network connectivity, increased salience network connectivity, and decreased central executive network connectivity in women with PMDD compared with control participants. A significant interaction between menstrual cycle phase and diagnosis was found in the central executive network for right posterior parietal cortex and left inferior lateral occipital cortex connectivity. A post hoc analysis revealed stronger FC during the midfollicular than the late-luteal phase of PMDD. ConclusionsAberrant FC in the 3 brain networks involved in PMDD may indicate vulnerability to experience affective and cognitive symptoms of the disorder.

Decreased default mode network functional connectivity with visual processing regions as potential biomarkers for delayed neurocognitive recovery: A resting-state fMRI study and machine-learning analysis.

The abnormal functional connectivity (FC) pattern of default mode network (DMN) may be key markers for early identification of various cognitive disorders. However, the whole-brain FC changes of DMN in delayed neurocognitive recovery (DNR) are still unclear. Our study was aimed at exploring the whole-brain FC patterns of all regions in DMN and the potential features as biomarkers for the prediction of DNR using machine-learning algorithms. Resting-state functional magnetic resonance imaging (fMRI) was conducted before surgery on 74 patients undergoing non-cardiac surgery. Seed-based whole-brain FC with 18 core regions located in the DMN was performed, and FC features that were statistically different between the DNR and non-DNR patients after false discovery correction were extracted. Afterward, based on the extracted FC features, machine-learning algorithms such as support vector machine, logistic regression, decision tree, and random forest were established to recognize DNR. The machine learning experiment procedure mainly included three following steps: feature standardization, parameter adjustment, and performance comparison. Finally, independent testing was conducted to validate the established prediction model. The algorithm performance was evaluated by a permutation test. We found significantly decreased DMN connectivity with the brain regions involved in visual processing in DNR patients than in non-DNR patients. The best result was obtained from the random forest algorithm based on the 20 decision trees (estimators). The random forest model achieved the accuracy, sensitivity, and specificity of 84.0, 63.1, and 89.5%, respectively. The area under the receiver operating characteristic curve of the classifier reached 86.4%. The feature that contributed the most to the random forest model was the FC between the left retrosplenial cortex/posterior cingulate cortex and left precuneus. The decreased FC of DMN with regions involved in visual processing might be effective markers for the prediction of DNR and could provide new insights into the neural mechanisms of DNR. : Chinese Clinical Trial Registry, ChiCTR-DCD-15006096.

Decreased Default Mode Network Connectivity Following 24 Hours of Capsaicin-induced Pain Persists During Immediate Pain Relief and Facilitation

Prolonged experimental pain models can help assess cortical mechanisms underlying the transition from acute to chronic pain such as resting-state functional connectivity (rsFC), especially in early stages. This crossover study determined the effects of 24-hour-capsaicin-induced pain on the default mode network rsFC, a major network in the dynamic pain connectome. Electroencephalographic rsFC measured by Granger causality was acquired from 24 healthy volunteers (12 women) at baseline, 1hour, and 24hours following the application of a control or capsaicin patch on the right forearm. The control patch was received maximum 1 week before the capsaicin patch. Following 24hours, the patch was cooled and later heated to assess rsFC changes in response to pain relief and facilitation, respectively. Compared to baseline, decreased rsFC at alpha oscillations (8-10Hz) was found following 1hour and 24hours of capsaicin application for connections projecting from medial prefrontal cortex (mPFC) and right angular gyrus (rAG) but not left angular gyrus (lAG) or posterior cingulate cortex (PCC): mPFC-PCC (1hour:P < .001, 24hours:P = .002), mPFC-rAG (1hour:P < .001, 24hours:P = .001), rAG-mPFC (1hour:P < .001, 24hours:P = .001), rAG-PCC (1hour:P < .001, 24hours:P = .004). Comparable decreased rsFC following 1hour and 24hours (P≤0.008) was found at beta oscillations, however, decreased projections from PCC were also found: PCC-rAG (P≤0.005) and PCC-lAG (P≤0.006). Pain NRS scores following 24hours (3.7±0.4) was reduced by cooling (0.3±0.1, P = .004) and increased by heating (4.8±0.6, P = .016). However, neither cooling nor heating altered rsFC. This study shows that 24hours of experimental pain induces a robust decrease in DMN connectivity that persists during pain relief or facilitation suggesting a possible shift to attentional and emotional processing in persistent pain. PerspectiveThis article shows decreased DMN connectivity that might reflect possible attentional and emotional changes during acute and prolonged pain. Understanding these changes could potentially help clinicians in developing therapeutic methods that can better target these attentional and emotional processes before developing into more persistent states.

Default mode network connectivity and treatment response in geriatric depression

<h3>Introduction</h3> Depression is associated with decreased default mode network (DMN) connectivity. Memantine is a non-competitive N-methyl-D-aspartate receptor antagonist that is currently FDA-approved for the treatment of cognitive symptoms in dementia. We evaluated the relationship between changes in DMN connectivity and improvement in depression in a subsample of our parent clinical trial comparing escitalopram/memantine (ESC/MEM) to escitalopram/placebo (ESC/PBO) in older depressed adults (NCT01902004). <h3>Methods</h3> Twenty-six participants with major depression (age >60 years) and subjective memory complaints underwent treatment with ESC/MEM (n=13) or ESC/PBO (n=13), and completed baseline and 3-month follow-up resting state magnetic resonance imaging scans. DMN maps were estimated using group independent analysis and dual regression; a single DMN component, comprising both anterior and posterior DMN key nodes (precuneus and medial prefrontal cortices), was identified. The 3-month change in DMN connectivity was calculated by subtracting the baseline DMN map from the 3-month DMN map. Multi-block partial least squares correlation analysis was used to evaluate the impact of treatment on DMN connectivity changes and their relationship with symptom improvement (as assessed by the MADRAS) at 3 months (controlling for age and sex). <h3>Results</h3> A significant latent variable was identified, reflecting DMN connectivity related to symptom improvement (p=0.01). Although there were no significant overall group differences in DMN connectivity changes, greater improvement in depressive symptoms was more strongly correlated with DMN connectivity increases in posterior and lateral DMN regions, as well as both increases and decreases in portions of the anterior DMN, in the ESC/MEM group (r=0.97, 95% confidence interval: 0.85-0.98) than in the ESC/PBO group (r=0.36, 95% confidence interval: 0.14-0.71). Figure 1 shows the DMN connectivity changes associated with symptom improvement (Red areas: increased DMN connectivity following treatment was more positively associated with symptom improvement in the ESC/MEM group than in the ESC/PBO group. Blue areas: decreased DMN connectivity following treatment was more positively associated with symptom improvement in the ESC/MEM group than in the ESC/PBO group). <h3>Conclusions</h3> Increased DMN connectivity in posterior and lateral nodes of the DMN following 3 months of treatment with ESC was associated with greater improvement in depression severity as assessed by the MADRS; however, this relationship was further enhanced with the addition of MEM than with placebo. This stronger relationship at 3 months from treatment initiation may be related to greater longer-term clinical and cognitive outcomes with ESC/MEM than with ESC/PBO. The present study adds to the limited literature on the role of the DMN in treatment-related effects in geriatric depression, and supports an improved engagement of brain circuitry beneficial to the amelioration of depressive symptoms with combined ESC/MEM treatment in older adults with depression and subjective memory complaints. <h3>Funding</h3> Sponsored by NIH grants R01MH097892 and AT009198, and National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR001881.

Out-of-step: brain-heart desynchronization in anxiety disorders.

Imaging studies in anxiety disorders (AD) show abnormal functional connectivity primarily in the salience network (SN), somatomotor network (SMN), and default mode network (DMN). However, it is not clear how precisely these network changes occur including their relation to psychopathological symptoms. Here, we show that the functional networks affected in AD overlap with cortical regions that receive visceral inputs (the so-called central/visceral autonomic network). Focusing on cardiac afferents, we suggest that network changes in AD may be due to reduced phase synchronization between ongoing neural and cardiac activity. This neuro-cardiac desynchronization occurs due to the abnormal phase resetting of neural activity at the onset of each heartbeat, as measured by a lower intertrial coherence and heartbeat-evoked potential. Biochemically, cardiac afferents reach subcortical serotonergic raphe nuclei and noradrenergic locus coeruleus (among others) which, in turn, are known to reciprocally modulate the DMN and SMN/SN on the cortical level. Consistent with the network changes in AD, decreases in serotonergic and noradrenergic activity are known to increase connectivity in both SMN and SN while, at the same time, they decrease DMN connectivity. SMN and SN increases, in turn, lead to increased emotional arousal/anxiety and bodily awareness whereas decreased DMN connectivity leads to an unstable sense-of-self in AD. Finally, we integrate our proposal with interoceptive predictive processing models suggesting neuro-cardiac desynchronization as a mechanism for "noisy" bottom-up information leading to a persistently uncertain bodily state in top-down models. In sum, integrating theories on active interference and hyperarousal, we propose a precise neuro-cardiac and biochemically -driven mechanisms for key psychopathological symptoms of AD.

Subacute effects of the psychedelic ayahuasca on the salience and default mode networks.

Neuroimaging studies have just begun to explore the acute effects of psychedelics on large-scale brain networks' functional organization. Even less is known about the neural correlates of subacute effects taking place days after the psychedelic experience. This study explores the subacute changes of primary sensory brain networks and networks supporting higher-order affective and self-referential functions 24 hours after a single session with the psychedelic ayahuasca. We leveraged task-free functional magnetic resonance imaging data 1 day before and 1 day after a randomized placebo-controlled trial exploring the effects of ayahuasca in naïve healthy participants (21 placebo/22 ayahuasca). We derived intra- and inter-network functional connectivity of the salience, default mode, visual, and sensorimotor networks, and assessed post-session connectivity changes between the ayahuasca and placebo groups. Connectivity changes were associated with Hallucinogen Rating Scale scores assessed during the acute effects. Our findings revealed increased anterior cingulate cortex connectivity within the salience network, decreased posterior cingulate cortex connectivity within the default mode network, and increased connectivity between the salience and default mode networks 1 day after the session in the ayahuasca group compared to placebo. Connectivity of primary sensory networks did not differ between groups. Salience network connectivity increases correlated with altered somesthesia scores, decreased default mode network connectivity correlated with altered volition scores, and increased salience default mode network connectivity correlated with altered affect scores. These findings provide preliminary evidence for subacute functional changes induced by the psychedelic ayahuasca on higher-order cognitive brain networks that support interoceptive, affective, and self-referential functions.

Activating attachment memories affects default mode network in a non-clinical sample with perceived dysfunctional parenting: An EEG functional connectivity study

Dysfunctional parenting constitutes a factor of psychopathological vulnerability affecting development both at neurobiological and psychological level. The default mode network (DMN), a large scale network for brain functional integration, is supposed to play a crucial role in those psychological functions altered by dysfunctional parenting. Here we investigate electroencephalography DMN functional connectivity in relation to perceived dysfunctional parenting (PDP) in a non-clinical sample. We hypothesized that participants with high PDP would exhibit decreased DMN connectivity after the activation of attachment memories. Our results support this hypothesis: participants with high PDP showed a decrease of theta connectivity between left temporoparietal junction and right anterior cingulate cortex after the activation of attachment memories, and, compared to participants with low PDP, showed a decrease of delta connectivity in the same brain areas. We interpret these decreased DMN connectivity in participants with high PDP as the “neurophysiological signature” of the impaired ability to mentalize their own relational experiences with significant others after the activation of early attachment memories. Thus, the activation of attachment memories in individuals exposed to dysfunctional parenting could lead to a transitory failure of functional brain connectivity and consequent disturbance of high integrative mental functions, such as emotional regulation and mentalization.

Alterations in ventral attention network connectivity in individuals with prediabetes

ABSTRACT Objective: Type 2 diabetes (T2D) is associated with aberrant neural functioning; however, the point at which brain function alterations occur in the progression of T2D is unknown. Here, we tested for differences in functional connectivity in adults with prediabetes and healthy individuals. We hypothesized that prediabetes, defined by glycated hemoglobin (HbA1c) 5.7–6.4% would be associated with disruptions in default mode network (DMN) connectivity. Methods: Fourteen brain networks were tested in 88 adults (prediabetes: n = 44; HbA1c = 5.8±0.2%; healthy: n = 44; HbA1c = 4.7±0.2%) matched for sex, age, and BMI. Results: We did not find differences in DMN connectivity between groups. Individuals with prediabetes showed stronger connectivity between the ventral attention network and (1) a visual network (p FWE = 0.0001); (2) a somatosensory network (p FWE = 0.0027). Individuals with healthy HbA1c showed stronger connectivity of the ventral attention network and (1) cingulo-opercular network (p FWE = 0.002); (2) a thalamic-striatal-visual network (p FWE = 0.001). Conclusions: Relative to individuals with prediabetes, those with a healthy HbA1c showed stronger connectivity between brain networks underlying self-control and attention to stimuli. In contrast, those with prediabetes demonstrated stronger connectivity between brain networks associated with sensory and attention to stimuli. While T2D reported contribute to decreased DMN connectivity, prediabetes is characterized by a shift in functional connectivity from a self-control network towards increasing connectivity in sensory network.

Levodopa imparts a normalizing effect on default-mode network connectivity in non-demented Parkinson’s disease

IntroductionParkinson’s disease (PD) is characterized with reduced dopamine level in the brain, resulting from the nigral degeneration. It is commonly accepted that the function of default mode network (DMN) is disturbed in PD, even in those who have no significant cognitive impairment. However, the relationship between the depletion of dopamine and DMN dysconnectivity is not fully clear. The aim of this study was to investigate the seed-based DMN connectivity and the influence of dopaminergic therapy on the DMN integrity in non-demented PD by using resting-state fMRI. Material and methodsResting-state fMRI data was collected from 24 non-demented PD patients before and after taking levodopa and 36 healthy controls (HCs). Functional connectivity (FC) was examined by a seed-based correlation approach. ResultsCompared with HCs, decreased DMN connectivity in PD patients was observed, a number of which were significantly improved after taking levodopa therapy. Moreover, by directly comparing the DMN connectivity between ON- and OFF-medication conditions, we found significantly enhanced FC in a set of regions of DMN in the ON- medication condition. Conversely, we also found that the PCC revealed decreased FC with left inferior temporal. ConclusionDMN connectivity was found to be impaired in no-demented PD patients, and levodopa has the ability to impart a normalizing effect on DMN connectivity.

Mindfulness-based therapy modulates default-mode network connectivity in patients with opioid dependence

Recently, mindfulness-based programs have shown promising clinical effects in the treatment of substance-use disorders (SUD). While several studies linked mindfulness to decreased default mode network (DMN) connectivity in meditators, only a few studies investigated its effects in patients with SUD. This study aimed to detect changes in DMN connectivity in opiate dependent patients receiving mindfulness based therapy (MBT) during their first month of treatment. Data from 32 patients that were assigned to MBT or treatment as usual (TAU) groups was investigated using resting-state functional MRI at 1.5 T before and after four weeks of treatment. Independent Component Analysis was used to investigate distinct (anterior vs. posterior) DMN subsystems. Connectivity changes after treatment were related to measures of impulsivity, distress tolerance and mindfulness. Increased mindfulness scores after treatment were found in patients receiving MBT compared to TAU. Within the anterior DMN, decreased right inferior frontal cortical connectivity was detected in patients who received MBT compared to TAU. In addition, within the MBT-group decreased right superior frontal cortex connectivity was detected after treatment. Inferior frontal cortex function was significantly associated with mindfulness measures. The data suggest that MBT can be useful during abstinence from opiates. In opiate-dependent patients distinct functional connectivity changes within the DMN are associated with MBT.

Resting-State Functional Connectivity and Psychotic-like Experiences in Childhood: Results From the Adolescent Brain Cognitive Development Study

BackgroundPsychotic-like experiences (PLEs) during childhood are associated with greater risk of developing a psychotic disorder (and other mental disorders), highlighting the importance of identifying neural correlates of childhood PLEs. Three major cortical networks—the cingulo-opercular network (CON), default mode network (DMN), and frontoparietal network—are consistently implicated in psychosis and PLEs in adults. However, it is unclear whether variation in functional connectivity is associated with PLEs in school-aged children. MethodsUsing hierarchical linear models, we examined the relationships between childhood PLEs and resting-state functional connectivity of the CON, DMN, and frontoparietal network, as well as the other networks, using an a priori network parcellation, using data from 9- to 11-year-olds (n = 3434) in the ABCD (Adolescent Brain Cognitive Development) study. We examined within-network, between-network, and subcortical connectivity. ResultsDecreased CON and DMN connectivity, as well as cinguloparietal (CPAR) network connectivity, were associated with greater PLEs, even after accounting for family history of psychotic disorders, internalizing symptoms, and cognitive performance. Decreased DMN connectivity was more strongly associated with increased delusional ideation, whereas decreased CON connectivity was more strongly associated with increased perceptual distortions. Increased CON-cerebellar and decreased CPAR-cerebellar connectivity were also associated with increased PLEs, and CPAR-cerebellar connectivity was more strongly associated with increased perceptual distortions. ConclusionsConsistent with hypotheses about the dimensionality of psychosis, our results provide novel evidence that neural correlates of PLEs, such as reduced functional connectivity of higher-order cognitive networks, are present even in school-aged children. The results provide further validation for continuity of PLEs across the life span.

Default mode network connectivity is associated with long-term clinical outcome in patients with schizophrenia.

This study investigated whether resting-state functional connectivity is associated with long-term clinical outcomes of patients with schizophrenia. Resting-state brain images were obtained from 79 outpatients with schizophrenia and 30 healthy controls (HC), using a 3 T-MRI scanner. All patients were 20–50 years old with >3 years' duration of illness and appeared clinically stable. We assessed their psychopathology using the 18-item Brief Psychiatric Rating Scale (BPRS-18) and divided them into “good,” “moderate,” and “poor” outcome (SZ-GO, SZ-MO, and SZ-PO) groups depending on BPRS-18 total score. We obtained individual functional connectivity maps between a seed region of the bilateral posterior cingulate cortex (PCC) and all other brain regions and compared the functional connectivity of the default mode network (DMN) among the HC and 3 schizophrenia outcome groups, with a voxel-wise threshold of P < .001 within a cluster-extent threshold of 114 voxels. Additionally, we assessed correlations between functional connectivity and BPRS-18 scores. The SZ-MO and SZ-PO groups showed decreased functional connectivity between PCC and right ventromedial prefrontal cortex (vmPFC), left middle cingulate cortex, and left frontopolar cortex (FPC) compared to the SZ-GO and HC groups. DMN connectivity in the right vmPFC and left FPC negatively correlated with subscale scores of the BPRS-18, except the negative symptoms subscale. In this study, poorer clinical outcomes in patients with schizophrenia were associated with decreased DMN connectivity. In particular, the decreased functional connectivity might be related to the severity of positive and mood symptoms rather than negative symptoms.

Acute tryptophan loading decreases functional connectivity between the default mode network and emotion‐related brain regions

It has been shown that the functional architecture of the default mode network (DMN) can be affected by serotonergic challenges and these effects may provide insights on the neurobiological bases of depressive symptomatology. To deepen our understanding of this possible interplay, we used a double-blind, randomized, cross-over design, with a control condition and two interventions to decrease (tryptophan depletion) and increase (tryptophan loading) brain serotonin synthesis. Resting-state fMRI from 85 healthy subjects was acquired for all conditions 3 hr after the ingestion of an amino acid mixture containing different amounts of tryptophan, the dietary precursor of serotonin. The DMN was derived for each participant and session. Permutation testing was performed to detect connectivity changes within the DMN as well as between the DMN and other brain regions elicited by the interventions. We found that tryptophan loading increased tryptophan plasma levels and decreased DMN connectivity with visual cortices and several brain regions involved in emotion and affect regulation (i.e., putamen, subcallosal cortex, thalamus, and frontal cortex). Tryptophan depletion significantly reduced tryptophan levels but did not affect brain connectivity. Subjective ratings of mood, anxiety, sleepiness, and impulsive choice were not strongly affected by any intervention. Our data indicate that connectivity between the DMN and emotion-related brain regions might be modulated by changes in the serotonergic system. These results suggest that functional changes in the brain associated with different brain serotonin levels may be relevant to understand the neural bases of depressive symptoms.

Intrinsic Functional Network Connectivity Is Associated With Clinical Symptoms and Cognition in Late-Life Depression

BackgroundLate-life depression (LLD) has been associated with alterations in intrinsic functional networks, best characterized in the default mode network (DMN), cognitive control network (CCN), and salience network. However, these findings often derive from small samples, and it is not well understood how network findings relate to clinical and cognitive symptomatology. MethodsWe studied 100 older adults (n = 79 with LLD, n = 21 nondepressed) and collected resting-state functional magnetic resonance imaging, clinical measures of depression, and performance on cognitive tests. We selected canonical network regions for each intrinsic functional network (DMN, CCN, and salience network) as seeds in seed-to-voxel analysis. We compared connectivity between the depressed and nondepressed groups and correlated connectivity with depression severity among depressed subjects. We then investigated whether the observed connectivity findings were associated with greater severity of common neuropsychiatric symptoms or poorer cognitive performance. ResultsLLD was characterized by decreased DMN connectivity to the frontal pole, a CCN region (Wald χ21 = 22.33, p < .001). No significant group differences in connectivity were found for the CCN or salience network. However, in the LLD group, increased CCN connectivity was associated with increased depression severity (Wald χ21 > 20.14, p < .001), greater anhedonia (Wald χ21 = 7.02, p = .008) and fatigue (Wald χ21 = 6.31, p = .012), and poorer performance on tests of episodic memory (Wald χ21 > 4.65, p < .031), executive function (Wald χ21 = 7.18, p = .007), and working memory (Wald χ21 > 4.29, p < .038). ConclusionsLLD is characterized by differences in DMN connectivity, while CCN connectivity is associated with LLD symptomology, including poorer performance in several cognitive domains.

PB1. Functional network alterations in multisystem atrophy (MSA)

Background In multisystem atrophy (MSA), the functional brain connectivity within cortical and subcortical networks and its clinical correlates is a challenging topic of research. Objective Assessment of functional brain connectivity alterations in MSA. Methods Whole-brain based ‘intrinsic functional connectivity’ MRI data were obtained from 22 MSA patients and 22 matched healthy controls, together with standardized clinical assessment and video-oculographic recordings (EyeLink®). Results MSA patients vs. controls showed significantly increased ponto-cerebellar functional connectivity and decreased default mode network connectivity ( p 0.05 , corrected). No differences were observed in the motor network. Saccadized smooth pursuit significantly correlated with increased functional ponto-cerebellar connectivity ( p 0.05 , corrected). Conclusion This intrinsic functional connectivity analysis supports a network-dependent combination of hyper- and hypoconnectivity states in MSA, in agreement with adaptive compensatory responses (hyperconnectivity) and a function disconnection syndrome (hypoconnectivity) ( Gorges et al., 2017 ) that may occur in a consecutive sequence.

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Neural correlates of childhood trauma with executive function in young healthy adults

The aim of this study was to investigate the relationship among childhood trauma, executive impairments, and altered resting-state brain function in young healthy adults. Twenty four subjects with childhood trauma and 24 age- and gender-matched subjects without childhood trauma were recruited. Executive function was assessed by a series of validated test procedures. Localized brain activity was evaluated by fractional amplitude of low frequency fluctuation (fALFF) method and compared between two groups. Areas with altered fALFF were further selected as seeds in subsequent functional connectivity analysis. Correlations of fALFF and connectivity values with severity of childhood trauma and executive dysfunction were analyzed as well. Subjects with childhood trauma exhibited impaired executive function as assessed by Wisconsin Card Sorting Test and Stroop Color Word Test. Traumatic individuals also showed increased fALFF in the right precuneus and decreased fALFF in the right superior temporal gyrus. Significant correlations of specific childhood trauma severity with executive dysfunction and fALFF value in the right precuneus were found in the whole sample. In addition, individuals with childhood trauma also exhibited diminished precuneus-based connectivity in default mode network with left ventromedial prefrontal cortex, left orbitofrontal cortex, and right cerebellum. Decreased default mode network connectivity was also associated with childhood trauma severity and executive dysfunction. The present findings suggest that childhood trauma is associated with executive deficits and aberrant default mode network functions even in healthy adults. Moreover, this study demonstrates that executive dysfunction is related to disrupted default mode network connectivity.

INTERACTIVE INFLUENCE OF DEPRESSION AND APOE-E4 ALLELE ON THE DEFAULT MODE NETWORK IN SUBJECTIVE COGNITIVE IMPAIRMENT

Functional connectivity in resting state network may represent a subtle deficit of brain function in the very early or presymptomatic stage of Alzheimer's disease (AD). Subjective cognitive impairment (SCI) as a preclinical stage of AD may demonstrate the functional compensation for brain declines. Depression may be manifested as an early symptom of AD. This study aimed to investigate the effect of depression on the resting state functional connectivity in SCI with and without APOE e4 allele. We consecutively recruited patients aged 55 and older who came to the memory clinic with subjective cognitive complaints but performed normally on neuropsychological tests (z > -1 in verbal delayed recall and z > -1.5 in the other cognitive tests). The final sample (n=180, mean age of 65.6 (SD 6.9) years, 127 females and 53 males) consisted of 134 APOE e4 noncarriers (e3/e3) and 46 carriers (e3/e4 or e4/e4). 21.1% of patients had depression. Presence of depression was defined by the total score > 17 in the Korean version of Geriatric depression scale. Resting state fMRI data were acquired using 3T MRI. Degrees of functional connectivity in four resting state networks (default mode network (DMN), executive control network, dorsal attention network, salience network) were calculated using the mean positive correlation coefficients between brain voxels and the seed in each network. Among four resting state networks, only DMN was associated with depression. SCI patients with depression had the decreased DMN connectivity compared to those without depression. Although the overall interaction effect was not statistically significant, the degree of the reduction in DMN connectivity tended to differ between APOE e4 noncarriers and carriers. Whereas in APOE e4 noncarriers depressive patients had significantly decreased connectivity compared to nondepressive patients, the difference was not significant in carriers. Depression in SCI altered the functional connectivity of DMN. However, this effect was evident only in APOE e4 noncarriers. While APOE e4 carriers with depression also had decreased functional connectivity, the degree of decrease was small. This may indicate APOE e4 carriers might develop the partial compensation process for their subtle changes in the brain.

Effect of catechol-O-methyltransferase Val158Met polymorphism on resting-state brain default mode network after acupuncture stimulation.

The effects of acupuncture can be characterized by clear individual differences. Several revealing studies suggest an underlying role of inherited genetic factor in interindividual variability in response to acupuncture treatment. It remains unclear, however, if the modulation of acupuncture on resting brain function is influenced by genetic factors. Catechol-o-methyltransferase (COMT) Val158Met polymorphism has been shown to regulate the resting brain network, especially in the default mode network (DMN), which is a target area that responds to acupuncture stimulation. Therefore, the present study investigated the effect of COMT Val158Met polymorphism on the modulation of acupuncture in DMN connectivity in healthy Chinese young adults. Using mixed-design ANOVA analysis, we found a significant interactive effect between acupuncture and the COMT gene. For subjects carrying the Val/Met genotype, acupuncture induced decreased DMN connectivity with the left middle frontal gyrus during the post-acupuncture stage compared with the pre-acupuncture stage, which was not observed in Val/Val homozygous subjects. These results demonstrated that during sustained periods after acupuncture stimulation, the brain network is likely under genetic control, and COMT might be a candidate gene that regulates the resting DMN response to acupuncture stimulation.