Posterior Default Mode Network Research Articles

Perioperative research into memory (PRiMe), part 2: Adult burns intensive care patients show altered structure and function of the default mode network

BackgroundLong-term cognitive impairment (LTCI) is experienced by up to two thirds of patients discharged from Burns Intensive Care Units (BICU), however little is known about its neurobiological basis. This study investigated if patients previously admitted to BICU showed structural and functional MRI changes of the Default Mode Network (DMN). MethodsFifteen patients previously admitted to BICU with a significant burns injury, and 15 matched volunteers, underwent structural and functional MRI scans. Functional connectivity, fractional anisotropy and cortical thickness of the main DMN subdivisions (anterior DMN (aDMN), posterior DMN (pDMN) and right (rTPJ) and left (lTPJ) temporo-parietal junctions) were compared between patients and volunteers, with differences correlated against cognitive performance. ResultsFunctional connectivity between rTPJ and pDMN (t = 2.91, p = 0.011) and between rTPJ and lTPJ (t = 3.18, p = 0.008) was lower in patients compared to volunteers. Functional connectivity between rTPJ and pDMN correlated with cognitive performance (r2 =0.33, p < 0.001). Mean fractional anisotropy of rTPJ (t = 2.70, p = 0.008) and lTPJ (T = 2.39, p = 0.015) was lower in patients but there was no difference in cortical thickness. ConclusionsPatients previously admitted to BICU show structural and functional disruption of the DMN. Since functional changes correlate with cognitive performance, this should direct further research into intensive care related cognitive impairment.

Altered functional connectivity of cerebellar subregions in male patients with obstructive sleep apnea: A resting-state fMRI study.

Previous studies have demonstrated impaired cerebellar function in patients with obstructive sleep apnea (OSA), which is associated with impaired cognition. However, the effects of OSA on resting-state functional connectivity (FC) in the cerebellum has not been determined. The purpose of this study was to investigate resting-state FC of the cerebellar subregions and its relevance to clinical symptoms in patients with OSA. Sixty-eight patients with OSA and seventy-two healthy controls (HCs) were included in the study. Eight subregions of the cerebellum were selected as regions of interest, and the FC values were calculated for each subregion with other voxels. A correlation analysis was performed to examine the relationship between clinical and cognitive data. Patients with OSA showed higher FC in specific regions, including the right lobule VI with the right posterior middle temporal gyrus and right angular gyrus, the right Crus I with the bilateral precuneus/left superior parietal lobule, and the right Crus II with the precuneus/right posterior cingulate cortex. Furthermore, the oxygen depletion index was negatively correlated with aberrant FC between the right Crus II and the bilateral precuneus / right posterior cingulate cortex in OSA patients (p = 0.004). The cerebellum is functionally lateralized and closely linked to the posterior default mode network. Higher FC is related to cognition, emotion, language, and sleep in OSA. Abnormal FC may offer new neuroimaging evidence and insights for a deeper comprehension of OSA-related alterations.

Social media distractions alter behavioral and neural patterns to global-local attention: The moderation effect of fear of missing out

Social media, including platforms such as Instagram or WeChat, has transformed several aspects our lives, ranging from global social interaction towards disrupted attentional patterns. Here, we explored how social media becomes a salient distractor intruding into global and local attention and the underlying neural pathways by means of functional magnetic resonance imaging (fMRI). Thirty-eight participants underwent a global-local attention paradigm combined with online social information distraction (SD), online nonsocial information distraction (NSD), and without information disturbance (baseline: BL). Results showed that SD decreased accuracy during both global and local attention processing. In contrast, NSD primarily decreased accuracy during global attention processing. On the neural level the SD effects were mirrored in decreased engagement of a core posterior default mode network node (DMN), i.e. the left precuneus. The effects at the network level were mirrored by the core region of the posterior DMN. At the same time, there was decreased activation of the Higher Visual Network during local attention processing. Variations in trait fear of missing out (FoMO) moderated the relationship between precuneus engagement and behavioral accuracy during local attention processing specifically during SD. Findings suggest that – compared to non-social media distraction - social online media information disrupts attention via the posterior DMN and stronger engagement of the higher visual cortex. Overall, this study provides valuable insights into the potential attention consequences of online social information intrusion and the neural mechanism underlying local attention disturbance in individuals with elevated levels of trait FoMO.

Impaired olfactory identification in dementia-free individuals is associated with the functional abnormality of the precuneus

ObjectiveOlfactory dysfunction indicates a higher risk of developing dementia. However, the potential structural and functional changes are still largely unknown. MethodsA total of 236 participants were enrolled, including 45 Alzheimer's disease (AD) individuals and 191dementia-free individuals. Detailed study methods, comprising neuropsychological assessment and olfactory identification test (University of Pennsylvania smell identification test, UPSIT), as well as structural and functional magnetic resonance imaging (MRI) were applied in this research. The dementia-free individuals were divided into two sub-groups based on olfactory score: dementia-free with olfactory dysfunction (DF-OD) sub-group and dementia-free without olfactory dysfunction (DF-NOD) sub-group. The results were analyzed for subsequent intergroup comparisons and correlations. The cognitive assessment was conducted again three years later. Results(i) At dementia-free stage, there was a positive correlation between olfactory score and cognitive function. (ii) In dementia-free group, the volume of crucial brain structures involved in olfactory recognition and processing (such as amygdala, entorhinal cortex and basal forebrain volumes) are positively associated with olfactory score. (iii) Compared to the DF-NOD group, the DF-OD group showed a significant reduction in olfactory network (ON) function. (iv) Compared to DF-NOD group, there were significant functional connectivity (FC) decline between PCun_L(R)_4_1 in the precuneus of posterior default mode network (pDMN) and the salience network (SN) in DF-OD group, and the FC values decreased with falling olfactory scores. Moreover, in DF-OD group, the noteworthy reduction in FC were observed between PCun_L(R)_4_1 and amygdala, which was a crucial component of ON. (v) The AD conversion rate of DF-OD was 29.41%, while the DF-NOD group was 12.50%. The structural and functional changes in the precuneus were also observed in AD and were more severe. ConclusionsIn addition to the olfactory circuit, the precuneus is a critical structure in the odor identification process, whose abnormal function underlies the olfactory identification impairment of dementia-free individuals.

Improved clinical outcome prediction in depression using neurodynamics in an emotional face-matching functional MRI task.

Approximately one in six people will experience an episode of major depressive disorder (MDD) in their lifetime. Effective treatment is hindered by subjective clinical decision-making and a lack of objective prognostic biomarkers. Functional MRI (fMRI) could provide such an objective measure but the majority of MDD studies has focused on static approaches, disregarding the rapidly changing nature of the brain. In this study, we aim to predict depression severity changes at 3 and 6 months using dynamic fMRI features. For our research, we acquired a longitudinal dataset of 32 MDD patients with fMRI scans acquired at baseline and clinical follow-ups 3 and 6 months later. Several measures were derived from an emotion face-matching fMRI dataset: activity in brain regions, static and dynamic functional connectivity between functional brain networks (FBNs) and two measures from a wavelet coherence analysis approach. All fMRI features were evaluated independently, with and without demographic and clinical parameters. Patients were divided into two classes based on changes in depression severity at both follow-ups. The number of coherence clusters (nCC) between FBNs, reflecting the total number of interactions (either synchronous, anti-synchronous or causal), resulted in the highest predictive performance. The nCC-based classifier achieved 87.5% and 77.4% accuracy for the 3- and 6-months change in severity, respectively. Furthermore, regression analyses supported the potential of nCC for predicting depression severity on a continuous scale. The posterior default mode network (DMN), dorsal attention network (DAN) and two visual networks were the most important networks in the optimal nCC models. Reduced nCC was associated with a poorer depression course, suggesting deficits in sustained attention to and coping with emotion-related faces. An ensemble of classifiers with demographic, clinical and lead coherence features, a measure of dynamic causality, resulted in a 3-months clinical outcome prediction accuracy of 81.2%. The dynamic wavelet features demonstrated high accuracy in predicting individual depression severity change. Features describing brain dynamics could enhance understanding of depression and support clinical decision-making. Further studies are required to evaluate their robustness and replicability in larger cohorts.

EEG resting state alpha dynamics predict an individual’s vulnerability to auditory hallucinations

AbstractTask-free brain activity exhibits spontaneous fluctuations between functional states, characterized by synchronized activation patterns in distributed resting-state (RS) brain networks. The temporal dynamics of the networks’ electrophysiological signatures reflect individual variations in brain activity and connectivity linked to mental states and cognitive functions and can predict or monitor vulnerability to develop psychiatric or neurological disorders. In particular, RS alpha fluctuations modulate perceptual sensitivity, attentional shifts, and cognitive control, and could therefore reflect a neural correlate of increased vulnerability to sensory distortions, including the proneness to hallucinatory experiences. We recorded 5 min of RS EEG from 33 non-clinical individuals varying in hallucination proneness (HP) to investigate links between task-free alpha dynamics and vulnerability to hallucinations. To this end, we used a dynamic brain state allocation method to identify five recurrent alpha states together with their spatiotemporal dynamics and most active brain areas through source reconstruction. The dynamical features of a state marked by activation in somatosensory, auditory, and posterior default-mode network areas predicted auditory and auditory-verbal HP, but not general HP, such that individuals with higher vulnerability to auditory hallucinations spent more time in this state. The temporal dynamics of spontaneous alpha activity might reflect individual differences in attention to internally generated sensory events and altered auditory perceptual sensitivity. Altered RS alpha dynamics could therefore instantiate a neural marker of increased vulnerability to auditory hallucinations.

Individual differences in the neural representation of cooperation and competition

Much evidence links the Big Five’s agreeableness to a propensity for cooperation and aggressiveness to a propensity for competition. However, the neural basis for these associations is unknown. In this functional magnetic resonance imaging study, using multivariate pattern analysis of data recorded during a computer game in which participants were required to construct target patterns either in cooperation or in competition with another person, we sought to determine how individual differences in neural representations of cooperative and competitive behavior relate to individual differences in agreeableness and aggressiveness. During cooperation, agreeableness was positively correlated with the consistency of spatial patterns of neural activation in the left temporoparietal junction (TPJ) and showed positive correlations with inter-subject similarity in the dynamics of neural responses in the posterior default mode network hub and areas involved in the regulation of attention, movement planning, and visual perception. During competition, aggressiveness was positively correlated with the consistency of spatial patterns in the left and right TPJ and showed positive correlations with neural dynamics in visual processing and movement regulation areas. These results are consistent with the assumption that agreeable individuals are more involved in cooperative interactions with others, whereas aggression-prone individuals are more involved in competitive interactions.

Functional connectivity between the habenula and posterior default mode network contributes to the response of the duloxetine effect in major depressive disorder.

This study aims to investigate the functional connectivity (FC) changes of the habenula (Hb) among patients with major depressive disorder (MDD) after 12 weeks of duloxetine treatment (MDD12). Patients who were diagnosed with MDD for the first time and were drug-naïve were recruited at baseline as cases. Healthy controls (HCs) matched for sex, age, and education level were also recruited at the same time. At baseline, all participants underwent resting-state functional MRI. FC analyses were performed using the Hb seed region of interest, and three groups including HCs, MDD group and MDD12 group were compared using whole-brain voxel-wise comparisons. Compared to the HCs, the MDD group had decreased FC between the Hb and the right anterior cingulate cortex at baseline. Compared to the HCs, the FC between the Hb and the left medial superior frontal gyrus decreased in the MDD12 group. Additionally, the FC between the left precuneus, bilateral cuneus and Hb increased in the MDD12 group than that in the MDD group. No significant correlation was found between HDRS-17 and the FC between the Hb, bilateral cuneus, and the left precuneus in the MDD12 group. Our study suggests that the FC between the post-default mode network and Hb may be the treatment mechanism of duloxetine and the treatment mechanisms and the pathogenesis of depression may be independent of each other.

Creative flow as optimized processing: Evidence from brain oscillations during jazz improvisations by expert and non-expert musicians

Using a creative production task, jazz improvisation, we tested alternative hypotheses about the flow experience: (A) that it is a state of domain-specific processing optimized by experience and characterized by minimal interference from task-negative default-mode network (DMN) activity versus (B) that it recruits domain-general task-positive DMN activity supervised by the fronto-parietal control network (FPCN) to support ideation. We recorded jazz guitarists' electroencephalograms (EEGs) while they improvised to provided chord sequences. Their flow-states were measured with the Core Flow State Scale. Flow-related neural sources were reconstructed using SPM12. Over all musicians, high-flow (relative to low-flow) improvisations were associated with transient hypofrontality. High-experience musicians’ high-flow improvisations showed reduced activity in posterior DMN nodes. Low-experience musicians showed no flow-related DMN or FPCN modulation. High-experience musicians also showed modality-specific left-hemisphere flow-related activity while low-experience musicians showed modality-specific right-hemisphere flow-related deactivations. These results are consistent with the idea that creative flow represents optimized domain-specific processing enabled by extensive practice paired with reduced cognitive control.

Electroconvulsive therapy disrupts functional connectivity between hippocampus and posterior default mode network

BackgroundThe mechanisms underlying memory deficits after electroconvulsive therapy (ECT) remain unclear but altered functional interactions between hippocampus and neocortex may play a role. ObjectivesTo test whether ECT reduces functional connectivity between hippocampus and posterior regions of the default mode network (DMN) and to examine whether altered hippocampal-neocortical functional connectivity correlates with memory impairment. A secondary aim was to explore if these connectivity changes are present 6 months after ECT. MethodsIn-patients with severe depression (n = 35) received bitemporal ECT. Functional connectivity of the hippocampus was probed with resting-state fMRI before the first ECT-session, after the end of ECT, and at a six-month follow-up. Memory was assessed with the Verbal Learning Test – Delayed Recall. Seed-based connectivity analyses established connectivity of four hippocampal seeds, covering the anterior and posterior parts of the right and left hippocampus. ResultsCompared to baseline, three of four hippocampal seeds became less connected to the core nodes of the posterior DMN in the week after ECT with Cohen's d ranging from −0.9 to −1.1. At the group level, patients showed post-ECT memory impairment, but individual changes in delayed recall were not correlated with the reduction in hippocampus-DMN connectivity. At six-month follow-up, no significant hippocampus-DMN reductions in connectivity were evident relative to pre-ECT, and memory scores had returned to baseline. ConclusionECT leads to a temporary disruption of functional hippocampus-DMN connectivity in patients with severe depression, but the change in connectivity strength is not related to the individual memory impairment.

Neurometabolic alterations in children and adolescents with functional neurological disorder

ObjectivesIn vivo magnetic resonance spectroscopy (MRS) was used to investigate neurometabolic homeostasis in children with functional neurological disorder (FND) in three regions of interest: supplementary motor area (SMA), anterior default mode network (aDMN), and posterior default mode network (dDMN). Metabolites assessed included N-acetyl aspartate (NAA), a marker of neuron function; myo-inositol (mI), a glial-cell marker; choline (Cho), a membrane marker; glutamate plus glutamine (Glx), a marker of excitatory neurotransmission; γ-aminobutyric acid (GABA), a marker of inhibitor neurotransmission; and creatine (Cr), an energy marker. The relationship between excitatory (glutamate and glutamine) and inhibitory (GABA) neurotransmitter (E/I) balance was also examined. MethodsMRS data were acquired for 32 children with mixed FND (25 girls, 7 boys, aged 10.00 to 16.08 years) and 41 healthy controls of similar age using both short echo point-resolved spectroscopy (PRESS) and Mescher-Garwood point-resolved spectroscopy (MEGAPRESS) sequences in the three regions of interest. ResultsIn the SMA, children with FND had lower NAA/Cr, mI/Cr (trend level), and GABA/Cr ratios. In the aDMN, no group differences in metabolite ratios were found. In the pDMN, children with FND had lower NAA/Cr and mI/Cr (trend level) ratios. While no group differences in E/I balance were found (FND vs. controls), E/I balance in the aDMN was lower in children with functional seizures—a subgroup within the FND group. Pearson correlations found that increased arousal (indexed by higher heart rate) was associated with lower mI/Cr in the SMA and pDMN. ConclusionsOur findings of multiple differences in neurometabolites in children with FND suggest dysfunction on multiple levels of the biological system: the neuron (lower NAA), the glial cell (lower mI), and inhibitory neurotransmission (lower GABA), as well as dysfunction in energy regulation in the subgroup with functional seizures.

Large-scale effective connectivity analysis reveals the existence of two mutual inhibitory systems in patients with major depression

It is posited that cognitive and affective dysfunction in patients with major depression disorder (MDD) may be caused by dysfunctional signal propagation in the brain. By leveraging dynamic causal modeling, we investigated large-scale directed signal propagation (effective connectivity) among distributed large-scale brain networks with 43 MDD patients and 56 healthy controls. The results revealed the existence of two mutual inhibitory systems: the anterior default mode network, auditory network, sensorimotor network, salience network and visual networks formed an “emotional” brain, while the posterior default mode network, central executive networks, cerebellum and dorsal attention network formed a “rational brain”. These two networks exhibited excitatory intra-system connectivity and inhibitory inter-system connectivity. Patients were characterized by potentiated intra-system connections within the “emotional/sensory brain”, as well as over-inhibition of the “rational brain” by the “emotional/sensory brain”. The hierarchical architecture of the large-scale effective connectivity networks was then analyzed using a PageRank algorithm which revealed a shift of the controlling role of the “rational brain” to the “emotional/sensory brain” in the patients. These findings inform basic organization of distributed large-scale brain networks and furnish a better characterization of the neural mechanisms of depression, which may facilitate effective treatment.

Abnormal functional activation during response inhibition in mild cognitive impairment: an fMRI study

AbstractBackgroundDeclines in response inhibition are observed both typical and atypical aging, i.e., mild cognitive impairment (MCI). Increased functional activation in frontoparietal regions during response inhibition has been interpreted to represent the emergence of a compensatory mechanism in older adulthood. While electrophysiology studies suggest the decline in response inhibition in MCI reflects a similar but amplified process as seen in normal aging this has not been examined thoroughly using functional MRI (fMRI).Method31 cognitively normal older adults (M age = 73.6, 9 male) and 22 adult patients with MCI (M age = 67.2, 14 male) performed a Go/NoGo task during an fMRI scan. Group differences in accuracy and reaction time were examined for Go and NoGo trials. Individual BOLD signal change during task fMRI was examined, then voxel‐wise group comparison was conducted for MCI vs. HC groups, using age, gender, education, and gray matter density as covariates. Permutation‐estimated cluster size at alpha &lt;.05 was defined to correct for errors of multiple comparisons.ResultBehaviorally, the MCI group made significantly more errors during NoGo and Go trials (p&lt;.001, p = .032, respectively), however, average reaction time did not differ significantly between groups. During NoGo trials, greater activation in the anterior default mode network (DMN), right dorsolateral prefrontal cortex (DLPFC), and motor areas was observed for MCI vs. HC, while during go trials, there was greater activation in DMN and right insula (corrected p&lt;0.05). However, when Go vs. NoGo trials were examined, MCI showed more activation in right insula and DLPFC, but less activation in the motor area at trend level (p&lt;0.05, uncorrected). While, there were no significant task performance differences between MCI subtypes (amnestic vs. non‐amnestic), amnestic MCI (aMCI) showed more activation in posterior DMN and dorsal attention area during NoGo trials (corrected p&lt;0.05).ConclusionMCI demonstrated significantly greater activation during both Go and NoGo trials and made significantly more errors in performance during both trial types as well. While the MCI subtypes did not exhibit differences in performance on the task, the aMCI exhibited significantly greater activation in multiple regions. Our findings suggested inefficient DMN suppression during task performance in the MCI cohort, especially in the aMCI subgroup.

Anterior and posterior default mode network functional connectivity and segregation in aging

AbstractBackgroundThe default mode network (DMN) supports memory performance and has been shown to be vulnerable to the effects of aging. The posterior DMN (pDMN) is an early region of amyloid‐β (Aβ) accumulation, which may lead to disrupted communication within/between subnetworks of the DMN. Using resting state functional connectivity (FC), we tested whether communication within and between the pDMN and anterior DMN (aDMN) were altered by aging and Aβ pathology and related to memory performance. We also tested segregation FC between the aDMN and pDMN.MethodData from 27 cognitively normal adults (69.6 years, 59% females) with resting state fMRI (rsfMRI), 18F‐florbetapir (FBP) PET to measure Aβ, and the Rey Auditory Verbal LearningTest (RAVLT) delayed recall to assess memory were analyzed. The rsfMRI data were preprocessed using CONN toolbox. ROI‐to‐ROI FC matrices were constructed for regions included in the aDMN and pDMN. We calculated: (1) the average FC within each network (Zw), (2) average FC between the aDMN and pDMN (Zb), and (3) network segregation [(Zw‐Zb)/Zw] for each DMN network. Global FBP SUVR was calculated as the mean across association cortical regions, and a cutoff of 1.11 was used to determine Aβ positivity. Analyses included the FC variables and their associations with age, Aβ, and memory.ResultOlder age was associated with reduced network segregation of the pDMN (r = ‐0.53, p = 0.004), and a trend level association for reduced within‐pDMN FC (r = ‐0.37, p = 0.057). Global FBP SUVR was not associated with FC or network segregation, and there was no significant difference in FC between Aβ groups (controlling for age). There was a trend‐level association between better memory performance and stronger FC between aDMN and pDMN (r = 0.37, p = 0.066; controlling for age and education).ConclusionResults demonstrated that aging is associated with specific FC disruptions of pDMN, leading to reduced specialization of processing as indexed by network segregation. Moreover, increased communication between DMN subnetworks may support memory in aging. Future analyses in a larger sample will further test the association between Alzheimer’s pathology and functional changes to DMN subnetworks.

Abnormal functional activation during response inhibition in mild cognitive impairment: an fMRI study

AbstractBackgroundDeclines in response inhibition are observed both typical and atypical aging, i.e., mild cognitive impairment (MCI). Increased functional activation in frontoparietal regions during response inhibition has been interpreted to represent the emergence of a compensatory mechanism in older adulthood. While electrophysiology studies suggest the decline in response inhibition in MCI reflects a similar but amplified process as seen in normal aging this has not been examined thoroughly using functional MRI (fMRI).Methods31 cognitively normal older adults (M age = 73.6, 9 male) and 22 adult patients with MCI (M age = 67.2, 14 male) performed a Go/NoGo task during an fMRI scan. Group differences in accuracy and reaction time were examined for Go and NoGo trials. Individual BOLD signal change during task fMRI was examined, then voxel‐wise group comparison was conducted for MCI vs. HC groups, using age, gender, education, and gray matter density as covariates. Permutation‐estimated cluster size at alpha &lt;.05 was defined to correct for errors of multiple comparisons.ResultsBehaviorally, the MCI group made significantly more errors during NoGo and Go trials (p&lt;.001, p = .032, respectively), however, average reaction time did not differ significantly between groups. During NoGo trials, greater activation in the anterior default mode network (DMN), right dorsolateral prefrontal cortex (DLPFC), and motor areas was observed for MCI vs. HC, while during go trials, there was greater activation in DMN and right insula (corrected p&lt;0.05). However, when Go vs. NoGo trials were examined, MCI showed more activation in right insula and DLPFC, but less activation in the motor area at trend level (p&lt;0.05, uncorrected). While, there were no significant task performance differences between MCI subtypes (amnestic vs. non‐amnestic), amnestic MCI (aMCI) showed more activation in posterior DMN and dorsal attention area during NoGo trials (corrected p&lt;0.05).ConclusionMCI demonstrated significantly greater activation during both Go and NoGo trials and made significantly more errors in performance during both trial types as well. While the MCI subtypes did not exhibit differences in performance on the task, the aMCI exhibited significantly greater activation in multiple regions. Our findings suggested inefficient DMN suppression during task performance in the MCI cohort, especially in the aMCI subgroup.

Default mode network sub‐systems connectivity in atypical Alzheimer’s disease

AbstractBackgroundDisruption of default mode network (DMN) connectivity is common in Alzheimer’s disease. We investigated cross‐sectional and one‐year longitudinal changes in DMN sub‐systems in atypical clinical presentations of AD, in relation to age and tau.MethodSixty‐four amyloid‐positive atypical AD (Aty‐AD) patients diagnosed with posterior cortical atrophy (n = 35) or logopenic progressive aphasia (n = 29) were recruited by the Neurodegenerative Research Group. Patients underwent structural and resting‐state functional MRI, and [18F]flortaucipir PET at baseline and one‐year follow‐up. 140 amyloid‐negative cognitively unimpaired (CU) individuals from the Mayo Clinic Study of Aging were included as controls. Global tau SUVR was calculated in a meta‐ROI including parietal, temporal, and occipital regions. DMN connectivity was calculated in native space for posterior (pDMN), ventral (vDMN), anterior ventral (avDMN) and anterior dorsal (adDMN) DMN sub‐systems using the dual regression method. A global measure of DMN connectivity, the Network Failure Quotient (NFQ), was calculated as (vDMN_to_pDMN+ adDMN_to_pDMN)/(pDMN+vDMN). Linear mixed‐effects models were computed for each DMN connectivity measure, including diagnosis (Aty‐AD, CU), age, time and their interaction, and a per‐person random effect. SPM paired t‐tests were run to compare baseline and follow‐up images in Aty‐AD and CU separately. Linear mixed‐effect models were run in the Aty‐AD cohort only to investigate the effect of global baseline tau SUVR on each DMN connectivity measure.ResultMixed‐effects models showed evidence of lower cross‐sectional pDMN and higher adDMN connectivity in Aty‐AD relative to CU, with no significant time effects (Fig. 1). While connectivity in all DMN sub‐systems declined with age in CU, connectivity was higher in older Aty‐AD patients relative to younger, particularly in vDMN and pDMN. A similar trend was observed for NFQ, which was significantly higher in Aty‐AD, with a negative age effect (Fig. 1). In Aty‐AD, voxel‐based analyses showed moderate evidence of decline in vDMN connectivity and increase in avDMN connectivity over time (Fig. 2). Greater baseline global tau SUVR was associated with lower vDMN connectivity, cross‐sectionally and longitudinally (Fig. 3).ConclusionDMN connectivity was altered in Aty‐AD, with strongest alterations in younger patients. The vDMN declined over time, suggesting a shift in DMN connectivity with disease progression that was likely related to tau pathology.

Default mode network sub‐systems connectivity in atypical Alzheimer’s disease

AbstractBackgroundDisruption of default mode network (DMN) connectivity is common in Alzheimer’s disease. We investigated cross‐sectional and one‐year longitudinal changes in DMN sub‐systems in atypical clinical presentations of AD, in relation to age and tau.MethodSixty‐four amyloid‐positive atypical AD (Aty‐AD) patients diagnosed with posterior cortical atrophy (n = 35) or logopenic progressive aphasia (n = 29) were recruited by the Neurodegenerative Research Group. Patients underwent structural and resting‐state functional MRI, and [18F]flortaucipir PET at baseline and one‐year follow‐up. 140 amyloid‐negative cognitively unimpaired (CU) individuals from the Mayo Clinic Study of Aging were included as controls. Global tau SUVR was calculated in a meta‐ROI including parietal, temporal, and occipital regions. DMN connectivity was calculated in native space for posterior (pDMN), ventral (vDMN), anterior ventral (avDMN) and anterior dorsal (adDMN) DMN sub‐systems using the dual regression method. A global measure of DMN connectivity, the Network Failure Quotient (NFQ), was calculated as (vDMN_to_pDMN+ adDMN_to_pDMN)/(pDMN+vDMN). Linear mixed‐effects models were computed for each DMN connectivity measure, including diagnosis (Aty‐AD, CU), age, time and their interaction, and a per‐person random effect. SPM paired t‐tests were run to compare baseline and follow‐up images in Aty‐AD and CU separately. Linear mixed‐effect models were run in the Aty‐AD cohort only to investigate the effect of global baseline tau SUVR on each DMN connectivity measure.ResultMixed‐effects models showed evidence of lower cross‐sectional pDMN and higher adDMN connectivity in Aty‐AD relative to CU, with no significant time effects (Fig. 1). While connectivity in all DMN sub‐systems declined with age in CU, connectivity was higher in older Aty‐AD patients relative to younger, particularly in vDMN and pDMN. A similar trend was observed for NFQ, which was significantly higher in Aty‐AD, with a negative age effect (Fig. 1). In Aty‐AD, voxel‐based analyses showed moderate evidence of decline in vDMN connectivity and increase in avDMN connectivity over time (Fig. 2). Greater baseline global tau SUVR was associated with lower vDMN connectivity, cross‐sectionally and longitudinally (Fig. 3).ConclusionDMN connectivity was altered in Aty‐AD, with strongest alterations in younger patients. The vDMN declined over time, suggesting a shift in DMN connectivity with disease progression that was likely related to tau pathology.

Tau accumulation within the default mode network as a predictor of longitudinal clinical decline in atypical Alzheimer’s disease

AbstractBackgroundIdentifying individuals with symptomatic Alzheimer’s disease (AD) at greater risk of steeper cognitive decline would allow professionals and loved‐ones to make better‐informed medical, support, and life‐planning decisions. In typical AD, the magnitude of cerebral tau accumulation in vivo predicts clinical deterioration. Despite its promise, the utility of tau PET in predicting cognitive decline in individuals with atypical clinical presentations of AD remains unclear. We examined the relationship between baseline tau PET signal and the rate of subsequent clinical decline across atypical AD syndromes.MethodFifty‐seven A/T/N‐positive patients (mean age = 64.13 ± 7.72; 24M/33F) with atypical syndromes of AD (19 Posterior Cortical Atrophy, 16 logopenic variant of Primary Progressive Aphasia, 16 dysexecutive AD, five early‐onset AD with single‐domain impairment, and one Corticobasal Syndrome) and 24 amyloid‐negative control participants were included in this study. All participants underwent 18F‐Flortaucipir (FTP) PET, amyloid PET, and structural MRI scans at baseline. The rate of clinical decline was quantified as the annualized change in Clinical Dementia Rating Sum‐of‐Boxes scores (CDR‐SB) at baseline and follow‐up visits (mean time interval = 1.24 ± 0.34 years). General linear model analyses were performed to examine the pattern of baseline cortical tau deposition in atypical AD patients and its relationship with the rate of clinical decline.ResultCompared with amyloid‐negative controls, atypical AD patients showed prominent FTP uptake in posterior cortical regions at baseline, including bilateral posterior cingulate cortex/precuneus and lateral temporo‐parietal cortices, which canonically constitute the posterior default mode network (DMN). A brain‐behavior regression analysis revealed widespread regions within the DMN where the magnitude of baseline FTP uptake predicted the rate of change in CDR‐SB, with anterior DMN regions (medial prefrontal and anterior temporal cortices) most strongly predicting clinical decline.ConclusionGreater baseline tau accumulation in the anterior DMN, possibly suggesting more extensive tau spread in this network, predicts faster clinical decline in atypical AD. This may serve as an imaging biomarker to guide prognostication for patients with atypical AD and their families and to inform the design of clinical trials, including potentially recruiting multiple clinical phenotypes of AD into a single trial.

Aberrant brain intra- and internetwork functional connectivity in children with Prader-Willi syndrome

PurposePrader-Willi syndrome (PWS) suffers from brain functional reorganization and developmental delays during childhood, but the underlying neurodevelopmental mechanism is unclear. This paper aims to investigate the intra- and internetwork functional connectivity (FC) changes, and their relationships with developmental delays in PWS children.MethodsResting-state functional magnetic resonance imaging datasets of PWS children and healthy controls (HCs) were acquired. Independent component analysis was used to acquire core resting-state networks (RSNs). The intra- and internetwork FC patterns were then investigated.ResultsIn terms of intranetwork FC, children with PWS had lower FC in the dorsal attention network, the auditory network, the medial visual network (VN) and the sensorimotor network (SMN) than HCs (FWE-corrected, p < 0.05). In terms of internetwork FC, PWS children had decreased FC between the following pairs of regions: posterior default mode network (DMN) and anterior DMN; posterior DMN and SMN; SMN and posterior VN and salience network and medial VN (FDR-corrected, p < 0.05). Partial correlation analyses revealed that the intranetwork FC patterns were positively correlated with developmental quotients in PWS children, while the internetwork FC patterns were completely opposite (p < 0.05). Intranetwork FC patterns showed an area under the receiver operating characteristic curve of 0.947, with a sensitivity of 96.15% and a specificity of 81.25% for differentiating between PWS and HCs.ConclusionImpaired intra- and internetwork FC patterns in PWS children are associated with developmental delays, which may result from neural pathway dysfunctions. Intranetwork FC reorganization patterns can discriminate PWS children from HCs.Registration number on the Chinese Clinical Trail RegistryChiCTR2100046551.

Resting state network connectivity is associated with cognitive flexibility performance in youth in the Adolescent Brain Cognitive Development Study

Cognitive flexibility is an executive functioning skill that develops in childhood, and when impaired, has transdiagnostic implications for psychiatric disorders. To identify how intrinsic neural architecture at rest is linked to cognitive flexibility performance, we used the data-driven method of independent component analysis (ICA) to investigate resting state networks (RSNs) and their whole-brain connectivity associated with levels of cognitive flexibility performance in children. We hypothesized differences by cognitive flexibility performance in RSN connectivity strength in cortico-striatal circuitry, which would manifest via the executive control network, right and left frontoparietal networks (FPN), salience network, default mode network (DMN), and basal ganglia network. We selected participants from the Adolescent Brain Cognitive Development (ABCD) Study who scored at the 25th, (“CF-Low”), 50th (“CF-Average”), or 75th percentiles (“CF-High”) on a cognitive flexibility task, were early to middle puberty, and did not exhibit significant psychopathology (n = 967, 47.9% female; ages 9–10). We conducted whole-brain ICA, identifying 14 well-characterized RSNs. Groups differed in connectivity strength in the right FPN, anterior DMN, and posterior DMN. Planned comparisons indicated CF-High had stronger connectivity between right FPN and supplementary motor/anterior cingulate than CF-Low. CF-High had more anti-correlated connectivity between anterior DMN and precuneus than CF-Average. CF-Low had stronger connectivity between posterior DMN and supplementary motor/anterior cingulate than CF-Average. Post-hoc correlations with reaction time by trial type demonstrated significant associations with connectivity. In sum, our results suggest childhood cognitive flexibility performance is associated with DMN and FPN connectivity strength at rest, and that there may be optimal levels of connectivity associated with task performance that vary by network.