Dynamical changes of interaction across functional brain communities during propofol-induced sedation.

It is crucial to understand how anesthetics disrupt information transmission within the whole-brain network and its hub structure to gain insight into the network-level mechanisms underlying propofol-induced sedation. However, the influence of propofol on functional integration, segregation, and community structure of whole-brain networks were still unclear. We recruited 12 healthy subjects and acquired resting-state functional magnetic resonance imaging data during 5 different propofol-induced effect-site concentrations (CEs): 0, 0.5, 1.0, 1.5, and 2.0 µg/ml. We constructed whole-brain functional networks for each subject under different conditions and identify community structures. Subsequently, we calculated the global and local topological properties of whole-brain network to investigate the alterations in functional integration and segregation with deepening propofol sedation. Additionally, we assessed the alteration of key nodes within the whole-brain community structure at each effect-site concentrations level. We found that global participation was significantly increased at high effect-site concentrations, which was mediated by bilateral postcentral gyrus. Meanwhile, connector hubs appeared and were located in posterior cingulate cortex and precentral gyrus at high effect-site concentrations. Finally, nodal participation coefficients of connector hubs were closely associated to the level of sedation. These findings provide valuable insights into the relationship between increasing propofol dosage and enhanced functional interaction within the whole-brain networks.

Functionality of arousal-regulating brain circuitry at rest predicts human cognitive abilities.

Arousal state is regulated by subcortical neuromodulatory nuclei, such as locus coeruleus, which send wide-reaching projections to cortex. Whether higher-order cortical regions have the capacity to recruit neuromodulatory systems to aid cognition is unclear. Here, we hypothesized that select cortical regions activate the arousal system, which, in turn, modulates large-scale brain activity, creating a functional circuit predicting cognitive ability. We utilized the Human Connectome Project 7T functional magnetic resonance imaging dataset (n = 149), acquired at rest with simultaneous eye tracking, along with extensive cognitive assessment for each subject. First, we discovered select frontoparietal cortical regions that drive large-scale spontaneous brain activity specifically via engaging the arousal system. Second, we show that the functionality of the arousal circuit driven by bilateral posterior cingulate cortex (associated with the default mode network) predicts subjects' cognitive abilities. This suggests that a cortical region that is typically associated with self-referential processing supports cognition by regulating the arousal system.

Does attachment in adolescence predict neural responses to handholding in adulthood? A functional magnetic resonance imaging study.

Objective: Early life experiences, including attachment-related experiences, inform internal working models that guide adult relationship behaviors. Few studies have examined the association between adolescent attachment and adult relationship behavior on a neural level. The current study examined attachment in adolescence and its associations with neural correlates of relationship behaviors in adulthood. Method: 85 participants completed the Adult Attachment Interview (AAI) at age 14. Ten years later, at age 24, participants underwent functional brain image when participants were under the threat of electric shock alone, holding the hand of a stranger, or their partner. Results: We found that adolescents who were securely attached at age 14 showed increased activation in regions commonly associated with cognitive, affective, and reward processing when they held the hand of their partner and stranger compared to being alone. Adolescents with higher preoccupied attachment scores showed decreased activation in similar regions only during the stranger handholding condition compared to being alone. Conclusions: These findings suggest that adolescent attachment predicts adult social relationship behaviors on a neural level, in regions largely consistent with previous literature. Broadly, this study has implications for understanding long-term links between attachment and adult relationship behaviors and has potential for informing intervention.

Micro-RNA profiles of pathology and resilience in posterior cingulate cortex of cognitively intact elders.

The posterior cingulate cortex (PCC) is a key hub of the default mode network underlying autobiographical memory retrieval, which falters early in the progression of Alzheimer's disease (AD). We recently performed RNA sequencing of post-mortem PCC tissue samples from 26 elderly Rush Religious Orders Study participants who came to autopsy with an ante-mortem diagnosis of no cognitive impairment but who collectively displayed a range of Braak I-IV neurofibrillary tangle stages. Notably, cognitively unimpaired subjects displaying high Braak stages may represent cognitive resilience to AD pathology. Transcriptomic data revealed elevated synaptic and ATP-related gene expression in Braak Stages III/IV compared with Stages I/II, suggesting these pathways may be related to PCC resilience. We also mined expression profiles for small non-coding micro-RNAs (miRNAs), which regulate mRNA stability and may represent an underexplored potential mechanism of resilience through the fine-tuning of gene expression within complex cellular networks. Twelve miRNAs were identified as differentially expressed between Braak Stages I/II and III/IV. However, the extent to which the levels of all identified miRNAs were associated with subject demographics, neuropsychological test performance and/or neuropathological diagnostic criteria within this cohort was not explored. Here, we report that a total of 667 miRNAs are significantly associated (rho > 0.38, P < 0.05) with subject variables. There were significant positive correlations between miRNA expression levels and age, perceptual orientation and perceptual speed. By contrast, higher miRNA levels correlated negatively with semantic and episodic memory. Higher expression of 15 miRNAs associated with lower Braak Stages I-II and 47 miRNAs were associated with higher Braak Stages III-IV, suggesting additional mechanistic influences of PCC miRNA expression with resilience. Pathway analysis showed enrichment for miRNAs operating in pathways related to lysine degradation and fatty acid synthesis and metabolism. Finally, we demonstrated that the 12 resilience-related miRNAs differentially expressed in Braak Stages I/II versus Braak Stages III/IV were predicted to regulate mRNAs related to amyloid processing, tau and inflammation. In summary, we demonstrate a dynamic state wherein differential PCC miRNA levels are associated with cognitive performance and post-mortem neuropathological AD diagnostic criteria in cognitively intact elders. We posit these relationships may inform miRNA transcriptional alterations within the PCC relevant to potential early protective (resilience) or pathogenic (pre-clinical or prodromal) responses to disease pathogenesis and thus may be therapeutic targets.

Posterior cingulate cortex hyperactivity in conversion disorder: a PET/MRI study.

Introduction: Several neuroimaging studies have been conducted to demonstrate the specific structural and functional brain correlations of conversion disorder. Although the findings of neuroimaging studies are not consistent, when evaluated as a whole, they suggest the presence of significant brain abnormalities. The aim of this study is to investigate brain metabolic activity through F-18 fluorodeoxyglucose PET/MRI in order to shed light on the neural correlates of conversion disorder. Methods: 20 patients diagnosed with conversion disorder were included in the study. Hamilton Depression and Anxiety Rating Scales, Somatosensory Amplification Scale and Somatoform Dissociation Scale were administered. Then, brain F-18 FDG-PET/MRI was performed.. Results: Hypermetabolism was found in posterior cingulate R, while glucose metabolisms of other brain regions were observed to be within the normal limits. When compared with the control group, statistically significant differences in z-scores were observed among all brain regions except for parietal superior R and cerebellum. No correlation was observed between the metabolisms of the left ACC and left medial PFC; left ACC and left temporal lateral cortex; cerebellum and left parietal inferior cortex despite the presence of positive correlations between these regions in the opposite hemisphere. Discussion: Results of the study suggest a potential involvement of the DMN which is associated with arousal and self-referential processing as well as regions associated with motor intention and self-agency.

Region-specific Cerebral Metabolic Alterations in Parkinson's Disease Patients With/without Mild Cognitive Impairment.

N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) are brain metabolites involved in some key neuronal functions within the brain, such as cognitive function. The aim of this study was to investigate whether Parkinson's disease (PD) with different cognitive status induces regional brain metabolite differences. 38 diagnosed PD patients, including 18 PD patients with normal cognitive (PDN), 20 PD subjects with cognitive impairment (PDMCI) and 25 healthy controls (HC) participated in this study. All subjects underwent a single-voxel proton MR spectroscopy (1H-MRS) on a 3T scanner. 1H-MRS were obtained from bilateral PCC, left thalamus and PFC regions in all subjects, respectively. Region-specific cerebral metabolic alterations existed in PD patients with different cognitive status. PDMCI patients showed a significant reduction of NAA, Cho and tCr in the PCC and left thalamus, compared to healthy controls; whereas lower levels of NAA and Cho in thalamus were found in PDN patients. Moreover, Cho and tCr levels were positively correlated with MMSE scores. Both NAA and tCr in PCC levels were positively correlated with MMSE and MoCA scores. The combination of thalamic and PCC metabolites showed a 75.6% accuracy in distinguishing PDMCI patients from PDN patients. This study provides preliminary evidence that thalamic, PCC and PFC neurometabolic alterations occur in PD patients with cognition decline. Findings of this study indicate that NAA and tCr abnormalities in PCC and thalamus might be used as a biomarker to track cognitive decline in Parkinson's disease in clinical settings.

Continuous inhalation of essential oil increases gray matter volume.

Research into the health benefits of scents is on the rise. However, little is known about the effects of continuous inhalation, such as wearing scents on clothing, on brain structure. Therefore, in this study, an intervention study was conducted on a total of 50 healthy female people, 28 in the intervention group and 22 in the control group, asking them to wear a designated rose scent on their clothes for a month. The effect of continuous inhalation of essential oil on the gray matter of the brain was measured by calculating changes in brain images of participants taken before and after the intervention using Magnetic Resonance Imaging (MRI). The results showed that the intervention increased the gray matter volume (GMV) of the whole brain and posterior cingulate cortex (PCC) subregion. On the other hand, the GMV of the amygdala and orbitofrontal cortex (OFC) did not change. This study is the first to show that continuous scent inhalation changes brain structure.

Modulation of hippocampal theta oscillations via deep brain stimulation of the parietal cortex depends on cognitive state.

The angular gyrus (AG) and posterior cingulate cortex (PCC) demonstrate extensive structural and functional connectivity with the hippocampus and other core recollection network regions. Consequently, recent studies have explored neuromodulation targeting these and other regions as a potential strategy for restoring function in memory disorders such as Alzheimer's Disease. However, determining the optimal approach for neuromodulatory devices requires understanding how parameters like selected stimulation site, cognitive state during modulation, and stimulation duration influence the effects of deep brain stimulation (DBS) on electrophysiological features relevant to episodic memory. We report experimental data examining the effects of high-frequency stimulation delivered to the AG or PCC on hippocampal theta oscillations during the memory encoding (study) or retrieval (test) phases of an episodic memory task. Results showed selective enhancement of anterior hippocampal slow theta oscillations with stimulation of the AG preferentially during memory retrieval. Conversely, stimulation of the PCC attenuated slow theta oscillations. We did not observe significant behavioral effects in this (open-loop) stimulation experiment, suggesting that neuromodulation strategies targeting episodic memory performance may require more temporally precise stimulation approaches.

Functionality of arousal-regulating brain circuitry at rest predicts human cognitive abilities.

Arousal state is regulated by subcortical neuromodulatory nuclei, such as locus coeruleus, which send wide-reaching projections to cortex. Whether higher-order cortical regions have the capacity to recruit neuromodulatory systems to aid cognition is unclear. Here, we hypothesized that select cortical regions activate the arousal system, which in turn modulates large-scale brain activity, creating a functional circuit predicting cognitive ability. We utilized the Human Connectome Project 7T functional magnetic resonance imaging dataset (N=149), acquired at rest with simultaneous eye tracking, along with extensive cognitive assessment for each subject. First, we discovered select frontoparietal cortical regions that drive large-scale spontaneous brain activity specifically via engaging the arousal system. Second, we show that the functionality of the arousal circuit driven by bilateral posterior cingulate cortex (associated with the default mode network) predicts subjects' cognitive abilities. This suggests that a cortical region that is typically associated with self-referential processing supports cognition by regulating the arousal system.

Dual role of α7 nicotinic acetylcholine receptors in the retrosplenial cortex for aversive memory acquisition and retrieval.

In the retrosplenial cortex (RSC), the role of cholinergic modulation via α7 nicotinic receptors and their involvement in memory is unknown. In recent years, the RSC has been shown to deteriorate in the early stages of Alzheimer's disease (AD). Likewise, the cholinergic system has been postulated as one of those responsible for cognitive impairment in patients with AD. Great interest has arisen in the study of α7 nicotinic receptors as more specific targets for the treatment of this disease. For this reason, we aim to study the role of α7 receptors of the RSC in memory processing. We infused a selective α7 receptor antagonist into the anterior part of the RSC (aRSC) to assess its role in different phases of aversive memory processing using an inhibitory avoidance task. We found that α7 nicotinic receptors are involved in memory acquisition and expression, but not in its consolidation. These results identify aRSC α7 nicotinic receptors as key players in aversive memory processing and highlight their significant potential as therapeutic targets for Alzheimer's disease.

Predicting performance in attention by measuring key metabolites in the PCC with 7T MRS.

The posterior cingulate cortex (PCC) is a key hub of the default mode network and is known to play an important role in attention. Using ultra-high field 7 Tesla magnetic resonance spectroscopy (MRS) to quantify neurometabolite concentrations, this exploratory study investigated the effect of the concentrations of myo-inositol (Myo-Ins), glutamate (Glu), glutamine (Gln), aspartate or aspartic acid (Asp) and gamma-amino-butyric acid (GABA) in the PCC on attention in forty-six healthy participants. Each participant underwent an MRS scan and cognitive testing, consisting of a trail-making test (TMT A/B) and a test of attentional performance. After a multiple regression analysis and bootstrapping for correction, the findings show that Myo-Ins and Asp significantly influence (p < 0.05) attentional tasks. On one hand, Myo-Ins shows it can improve the completion times of both TMT A and TMT B. On the other hand, an increase in aspartate leads to more mistakes in Go/No-go tasks and shows a trend towards enhancing reaction time in Go/No-go tasks and stability of alertness without signal. No significant (p > 0.05) influence of Glu, Gln and GABA was observed.

Functional connectivity of the posterior cingulate cortex in autism spectrum disorder.

The purpose of this study was to assess the functional connectivity of the posterior cingulate cortex in autism spectrum disorder (ASD). We used resting-state functional magnetic resonance imaging (rsfMRI) brain scans of adolescents diagnosed with ASD and a neurotypical control group. The Autism Brain Imaging Data Exchange (ABIDE) consortium was utilized to acquire data from the University of Michigan (145 subjects) and data from the New York University (183 subjects). The posterior cingulate cortex showed reduced connectivity with the anterior cingulate cortex for the ASD group compared to the control group. These two brain regions have previously both been linked to ASD symptomology. Specifically, the posterior cingulate cortex has been associated with behavioral control and executive functions, which appear to be responsible for the repetitive and restricted behaviors (RRB) in ASD. Our findings support previous data indicating a neurobiological basis of the disorder, and the specific functional connectivity changes involving the posterior cingulate cortex and anterior cingulate cortex may be a potential neurobiological biomarker for the observed RRBs in ASD.

Intrinsic connectivity demonstrates a shared role of the posterior cingulate for cue reactivity in both gambling and cocaine use disorders.

Cue reactivity is relevant across addictive disorders as a process relevant to maintenance, relapse, and craving. Understanding the neurobiological foundations of cue reactivity across substance and behavioral addictions has important implications for intervention development. The present study used intrinsic connectivity distribution methods to examine functional connectivity during a cue-exposure fMRI task involving gambling, cocaine and sad videos in 22 subjects with gambling disorder, 24 with cocaine use disorder, and 40 healthy comparison subjects. Intrinsic connectivity distribution implicated the posterior cingulate cortex (PCC) at a stringent whole-brain threshold. Post-hoc analyses investigating the nature of the findings indicated that individuals with gambling disorder and cocaine use disorder exhibited decreased connectivity in the posterior cingulate during gambling and cocaine cues, respectively, as compared to other cues and compared to other groups. Brain-related cue reactivity in substance and behavioral addictions involve PCC connectivity in a content-to-disorder specific fashion. The findings suggesting that PCC-related circuitry underlies cue reactivity across substance and behavioral addictions suggests a potential biomarker for targeting in intervention development.

Neural Correlates of Positive Outcome Expectancy for Aggression: Evidence from Voxel-Based Morphometry and Resting-State Functional Connectivity Analysis.

Positive outcome expectancy is a crucial cognitive factor influencing aggression, yet its neural basis remains unclear. Therefore, the present study combined voxel-based morphometry (VBM) with a resting-state functional connectivity (RSFC) analysis to investigate the brain correlates of positive outcome expectancy in aggression in young people. In the VBM analysis, multiple linear regression was conducted to explore the relationship between individual differences in aggressive positive outcome expectancy and regional gray matter volume (GMV) among 325 undergraduate students. For the RSFC analysis, seed regions were selected based on the results of the VBM analysis. Subsequently, multiple linear regression was employed to examine whether a significant correlation existed between individual differences in aggressive positive outcome expectancy and the RSFC of seed regions with other brain regions in 304 undergraduate students. The findings indicated that aggressive positive outcome expectancy was positively correlated with GMV in the posterior cingulate cortex (PCC), right temporoparietal junction (TPJ), and medial prefrontal cortex (MPFC). Moreover, it was also positively associated with RSFC between the PCC and the left dorsolateral prefrontal cortex (DLPFC). The prediction analysis indicated robust relationships between aggressive positive outcome expectancy and the GMV in the PCC, right TPJ, as well as the RSFC between the PCC and the left DLPFC. Our research provides the initial evidence for the neural basis of positive outcome expectancy in aggression, suggesting the potential role of the PCC as a hub in its neural network.