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.

Signatures of Electrical Stimulation Driven Network Interactions in the Human Limbic System.

Stimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain stimulation therapy, is involved in emotion and memory processing. Previous anatomic, neurophysiological, and functional studies suggest distinct subsystems within the limbic network (Rolls, 2015). Studies using intracranial electrical stimulation, however, have emphasized the similarities of the evoked waveforms across the limbic network. We test whether these subsystems have distinct stimulation-driven signatures. In eight patients (four male, four female) with drug-resistant epilepsy, we stimulated the limbic system with single-pulse electrical stimulation. Reliable corticocortical evoked potentials (CCEPs) were measured between hippocampus and the posterior cingulate cortex (PCC) and between the amygdala and the anterior cingulate cortex (ACC). However, the CCEP waveform in the PCC after hippocampal stimulation showed a unique and reliable morphology, which we term the "limbic Hippocampus-Anterior nucleus of the thalamus-Posterior cingulate, HAP-wave." This limbic HAP-wave was visually distinct and separately decoded from the CCEP waveform in ACC after amygdala stimulation. Diffusion MRI data show that the measured end points in the PCC overlap with the end points of the parolfactory cingulum bundle rather than the parahippocampal cingulum, suggesting that the limbic HAP-wave may travel through fornix, mammillary bodies, and the anterior nucleus of the thalamus (ANT). This was further confirmed by stimulating the ANT, which evoked the same limbic HAP-wave but with an earlier latency. Limbic subsystems have unique stimulation-evoked signatures that may be used in the future to help network pathology diagnosis.SIGNIFICANCE STATEMENT The limbic system is often compromised in diverse clinical conditions, such as epilepsy or Alzheimer's disease, and characterizing its typical circuit responses may provide diagnostic insight. Stimulation-evoked waveforms have been used in the motor system to diagnose circuit pathology. We translate this framework to limbic subsystems using human intracranial stereo EEG (sEEG) recordings that measure deeper brain areas. Our sEEG recordings describe a stimulation-evoked waveform characteristic to the memory and spatial subsystem of the limbic network that we term the "limbic HAP-wave." The limbic HAP-wave follows anatomic white matter pathways from hippocampus to thalamus to the posterior cingulum and shows promise as a distinct biomarker of signaling in the human brain memory and spatial limbic network.

Motor performance and functional connectivity between the posterior cingulate cortex and supplementary motor cortex in bipolar and unipolar depression.

Although implicated in unsuccessful treatment, psychomotor deficits and their neurobiological underpinnings in bipolar (BD) and unipolar (UD) depression remain poorly investigated. Here, we hypothesized that motor performance deficits in depressed patients would relate to basal functional coupling of the hand primary motor cortex (M1) and the posterior cingulate cortex (PCC) with the supplementary motor area (SMA). We performed a longitudinal, naturalistic study in BD, UD and matched healthy controls comprising of two resting-state functional MRI measurements five weeks apart and accompanying assessments of motor performance using a finger tapping task (FTT). A subject-specific seed-based analysis describing functional connectivity between PCC-SMA as well as M1-SMA was conducted. The basal relationships with motor performance were investigated using linear regression models and all measures were compared across groups. Performance in FTT was impaired in BD in comparison to HC in both sessions. Behavioral performance across groups correlated significantly with resting state functional coupling of PCC-SMA, but not of M1-SMA regions. This relationship was partially reflected in a reduced PCC-SMA connectivity in BD vs HC in the second session. Exploratory evaluation of large-scale networks coupling (SMN-DMN) exhibited no correlation to motor performance. Our results shed new light on the association between the degree of disruption in the SMA-PCC anticorrelation and the level of motor impairment in BD.

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.

Exploring Information Flow from Posteromedial Cortex during Visuospatial Working Memory: A Magnetoencephalography Study.

The posteromedial cortex (PMC) is a major hub of the brain's default mode network, and is implicated in a broad range of internally driven cognitions, including visuospatial working memory. However, its precise contribution to these cognitive processes remains unclear. Using MEG, we measured PMC activity in healthy human participants (young adults of both sexes) while they performed a visuospatial working memory task. Multivariate pattern classification analyses revealed stimulus-related information during encoding and retrieval in a set of a priori defined cortical ROIs, including prefrontal, occipital, and ventrotemporal cortices, in addition to PMC. We measured the extent to which this stimulus information was exchanged between areas in an information flow analysis, measuring Granger-causal relationships between areas over time. Consistent with the visual nature of the task, information from occipital cortex shaped other regions across most epochs. However, the PMC shaped object representations in occipital and prefrontal cortices during visuospatial working memory, influencing occipital cortex during retrieval and PFC across all task epochs. Our findings are consistent with a proposed role for the PMC in the representation of internal content, including remembered information, and in the comparison of external stimuli with remembered material.SIGNIFICANCE STATEMENT The human brain operates as a collection of highly interconnected regions. Mapping the function of this interconnectivity, as well as the specializations within different regions, is central to understanding the neural processes underlying cognition. The posteromedial cortex (PMC) is a highly connected cortical region, implicated in visuospatial working memory, although its precise contribution remains unclear. We measured the activity of PMC during a visuospatial working memory task, testing how different regions represented the stimuli, and whether these representations were driven by other cortical regions. We found that PMC influenced stimulus information in other regions across all task phases, suggesting that PMC plays a key role in shaping stimulus representations during visuospatial working memory.

Neural correlates of changing food choices while bypassing values.

Current theories suggest that altering choices requires value modification. To investigate this, normal-weight female participants' food choices and values were tested before and after an approach-avoidance training (AAT), while neural activity was recorded during the choice task using functional magnetic resonance imaging (fMRI). During AAT, participants consistently approached low- while avoiding high-calorie food cues. AAT facilitated low-calorie food choices, leaving food values unchanged. Instead, we observed a shift in indifference points, indicating the decreased contribution of food values in food choices. Training-induced choice shifts were associated with increased activity in the posterior cingulate cortex (PCC). In contrast, the medial PFC activity was not changed. Additionally, PCC gray matter density predicted individual differences in training-induced functional changes, suggesting anatomic predispositions to training impact. Our findings demonstrate neural mechanisms underlying choice modulation independent of valuation-related processes, which has substantial theoretical significance for decision-making frameworks and translational implications for health-related decisions resilient to value shifts.

The human posterior cingulate, retrosplenial, and medial parietal cortex effective connectome, and implications for memory and navigation.

The human posterior cingulate, retrosplenial, and medial parietal cortex are involved in memory and navigation. The functional anatomy underlying these cognitive functions was investigated by measuring the effective connectivity of these Posterior Cingulate Division (PCD) regions in the Human Connectome Project-MMP1 atlas in 171 HCP participants, and complemented with functional connectivity and diffusion tractography. First, the postero-ventral parts of the PCD (31pd, 31pv, 7m, d23ab, and v23ab) have effective connectivity with the temporal pole, inferior temporal visual cortex, cortex in the superior temporal sulcus implicated in auditory and semantic processing, with the reward-related vmPFC and pregenual anterior cingulate cortex, with the inferior parietal cortex, and with the hippocampal system. This connectivity implicates it in hippocampal episodic memory, providing routes for "what," reward and semantic schema-related information to access the hippocampus. Second, the antero-dorsal parts of the PCD (especially 31a and 23d, PCV, and also RSC) have connectivity with early visual cortical areas including those that represent spatial scenes, with the superior parietal cortex, with the pregenual anterior cingulate cortex, and with the hippocampal system. This connectivity implicates it in the "where" component for hippocampal episodic memory and for spatial navigation. The dorsal-transitional-visual (DVT) and ProStriate regions where the retrosplenial scene area is located have connectivity from early visual cortical areas to the parahippocampal scene area, providing a ventromedial route for spatial scene information to reach the hippocampus. These connectivities provide important routes for "what," reward, and "where" scene-related information for human hippocampal episodic memory and navigation. The midcingulate cortex provides a route from the anterior dorsal parts of the PCD and the supracallosal part of the anterior cingulate cortex to premotor regions.

Sleep Deficits Inter-Link Lower Basal Forebrain-Posterior Cingulate Connectivity and Perceived Stress and Anxiety Bidirectionally in Young Men.

BACKGROUND: The basal nucleus of Meynert (BNM), a primary source of cholinergic projections to the cortex, plays key roles in regulating the sleep-wake cycle and attention. Sleep deficit is associated with impairment in cognitive and emotional functions. However, whether or how cholinergic circuit, sleep, and cognitive/emotional dysfunction are inter-related remains unclear. METHODS: We curated the Human Connectome Project data and explored BNM resting state functional connectivities (rsFC) in relation to sleep deficit, based on the Pittsburgh Sleep Quality Index (PSQI), cognitive performance, and subjective reports of emotional states in 687 young adults (342 women). Imaging data were processed with published routines and evaluated at a corrected threshold. We assessed the correlation between BNM rsFC, PSQI, and clinical measurements with Pearson regressions and their inter-relationships with mediation analyses. RESULTS: In whole-brain regressions with age and alcohol use severity as covariates, men showed lower BNM rsFC with the posterior cingulate cortex (PCC) in correlation with PSQI score. No clusters were identified in women at the same threshold. Both BNM-PCC rsFC and PSQI score were significantly correlated with anxiety, perceived stress, and neuroticism scores in men. Moreover, mediation analyses showed that PSQI score mediated the relationship between BNM-PCC rsFC and these measures of negative emotions bidirectionally in men. CONCLUSIONS: Sleep deficit is associated with negative emotions and lower BNM rsFC with the PCC. Negative emotional states and BNM-PCC rsFC are bidirectionally related through poor sleep quality. These findings are specific to men, suggesting potential sex differences in the neural circuits regulating sleep and emotional states.

Early-in-life isoflurane exposure alters resting-state functional connectivity in juvenile non-human primates.

BACKGROUND: Clinical studies suggest that anaesthesia exposure early in life affects neurobehavioural development. We designed a non-human primate (NHP) study to evaluate cognitive, behavioural, and brain functional and structural alterations after isoflurane exposure during infancy. These NHPs displayed decreased close social behaviour and increased astrogliosis in specific brain regions, most notably in the amygdala. Here we hypothesise that resting-state functional connectivity MRI can detect alterations in connectivity of brain areas that relate to these social behaviours and astrogliosis. METHODS: Imaging was performed in 2-yr-old NHPs under light anaesthesia, after early-in-life (postnatal days 6-12) exposure to 5 h of isoflurane either one or three times, or to room air. Brain images were segmented into 82 regions of interest; the amygdala and the posterior cingulate cortex were chosen for a seed-based resting-state functional connectivity MRI analysis. RESULTS: We found differences between groups in resting-state functional connectivity of the amygdala and the auditory cortices, medial premotor cortex, and posterior cingulate cortex. There were also alterations in resting-state functional connectivity between the posterior cingulate cortex and secondary auditory, polar prefrontal, and temporal cortices, and the anterior insula. Relationships were identified between resting-state functional connectivity alterations and the decrease in close social behaviour and increased astrogliosis. CONCLUSIONS: Early-in-life anaesthesia exposure in NHPs is associated with resting-state functional connectivity alterations of the amygdala and the posterior cingulate cortex with other brain regions, evident at the juvenile age of 2 yr. These changes in resting-state functional connectivity correlate with the decrease in close social behaviour and increased astrogliosis. Using resting-state functional connectivity MRI to study the neuronal underpinnings of early-in-life anaesthesia-induced behavioural alterations could facilitate development of a biomarker for anaesthesia-induced developmental neurotoxicity.

Network Analysis of Human Brain Connectivity Reveals Neural Fingerprints of a Compositionality Bias in Signaling Systems.

Compositionality is a hallmark of human language and other symbolic systems: a finite set of meaningful elements can be systematically combined to convey an open-ended array of ideas. Compositionality is not uniformly distributed over expressions in a language or over individuals' communicative behavior: at both levels, variation is observed. Here, we investigate the neural bases of interindividual variability by probing the relationship between intrinsic characteristics of brain networks and compositional behavior. We first collected functional resting-state and diffusion magnetic resonance imaging data from a large participant sample (N = 51). Subsequently, participants took part in two signaling games. They were instructed to learn and reproduce an auditory symbolic system of signals (tone sequences) associated with affective meanings (human faces expressing emotions). Signal-meaning mappings were artificial and had to be learned via repeated signaling interactions. We identified a temporoparietal network in which connection length was related to the degree of compositionality introduced in a signaling system by each player. Graph-theoretic analysis of resting-state functional connectivity revealed that, within that network, compositional behavior was associated with integration measures in 2 semantic hubs: the left posterior cingulate cortex and the left angular gyrus. Our findings link individual variability in compositional biases to variation in the anatomy of semantic networks and in the functional topology of their constituent units.

Regional grey matter volume in the posterior cingulate cortex predicts positive risk-taking: A moderation model.

Positive risk-taking is a crucial element of individual creativity and social development. However, little is known regarding the relation between individual neural differences and positive risk-taking. In addition, critical thinking (CT) and gender have been proven to be two important individual-specific factors associated with risk-taking behaviour, and different levels of CT and gender may have diverse effects on the relationship between brain structure and positive risk-taking. The present study examined the relationship between positive risk-taking and regional grey matter volume (rGMV) in 292 healthy participants. The results showed that positive risk-taking was significantly positively associated with the rGMV of the posterior cingulate cortex (PCC). In addition, this study investigated individual differences in critical thinking and found that it moderated the relationship between rGMV and positive risk-taking. Individuals with lower CT had a stronger association between rGMV and positive risk-taking. Further analysis showed that for males, a greater rGMV was significantly linked to higher positive risk-taking tendency. These findings suggest that PCC evaluates risk and serves as a behavioural adaptation hub for positive risk-taking. This study thereby contributes to the literature on individual differences in brain structure and risk-taking by elucidating the moderating effects of CT and gender in healthy adults.

Spatially Adjacent Regions in Posterior Cingulate Cortex Represent Familiar Faces at Different Levels of Complexity.

Extensive research has shown that perceptual information of faces is processed in a network of hierarchically-organized areas within ventral temporal cortex. For familiar and famous faces, perceptual processing of faces is normally accompanied by extraction of semantic knowledge about the social status of persons. Semantic processing of familiar faces could entail progressive stages of information abstraction. However, the cortical mechanisms supporting multistage processing of familiar faces have not been characterized. Here, using an event-related fMRI experiment, familiar faces from four celebrity groups (actors, singers, politicians, and football players) and unfamiliar faces were presented to the human subjects (both males and females) while they were engaged in a face categorization task. We systematically explored the cortical representations for faces, familiar faces, subcategories of familiar faces, and familiar face identities using whole-brain univariate analysis, searchlight-based multivariate pattern analysis (MVPA), and functional connectivity analysis. Convergent evidence from all these analyses revealed a set of overlapping regions within posterior cingulate cortex (PCC) that contained decodable fMRI responses for representing different levels of semantic knowledge about familiar faces. Our results suggest a multistage pathway in PCC for processing semantic information of faces, analogous to the multistage pathway in ventral temporal cortex for processing perceptual information of faces.SIGNIFICANCE STATEMENT Recognizing familiar faces is an important component of social communications. Previous research has shown that a distributed network of brain areas is involved in processing the semantic information of familiar faces. However, it is not clear how different levels of semantic information are represented in the brain. Here, we evaluated the multivariate response patterns across the entire cortex to discover the areas that contain information for familiar faces, subcategories of familiar faces, and identities of familiar faces. The searchlight maps revealed that different levels of semantic information are represented in topographically adjacent areas within posterior cingulate cortex (PCC). The results suggest that semantic processing of faces is mediated through progressive stages of information abstraction in PCC.

Hypoxia alters posterior cingulate cortex metabolism during a memory task: A 1H fMRS study.

Environmental hypoxia (fraction of inspired oxygen (FIO2) ∼ 0.120) is known to trigger a global increase in cerebral blood flow (CBF). However, regionally, a heterogeneous response is reported, particularly within the posterior cingulate cortex (PCC) where decreased CBF is found after two hours of hypoxic exposure. Furthermore, hypoxia reverses task-evoked BOLD signals within the PCC, and other regions of the default mode network, suggesting a reversal of neurovascular coupling. An alternative explanation is that the neural architecture supporting cognitive tasks is reorganised. Therefore, to confirm if this previous result is neural or vascular in origin, a measure of neural activity that is not haemodynamic-dependant is required. To achieve this, we utilised functional magnetic resonance spectroscopy to probe the glutamate response to memory recall in the PCC during normoxia (FIO2 = 0.209) and after two hours of poikilocapnic hypoxia (FIO2 = 0.120). We also acquired ASL-based measures of CBF to confirm previous findings of reduced CBF within the PCC in hypoxia. Consistent with previous findings, hypoxia induced a reduction in CBF within the PCC and other regions of the default mode network. Under normoxic conditions, memory recall was associated with an 8% increase in PCC glutamate compared to rest (P = 0.019); a change which was not observed during hypoxia. However, exploratory analysis of other neurometabolites showed that PCC glucose was reduced during hypoxia compared to normoxia both at rest (P = 0.039) and during the task (P = 0.046). We conclude that hypoxia alters the activity-induced increase in glutamate, which may reflect a reduction in oxidative metabolism within the PCC. The reduction in glucose in hypoxia reflects continued metabolism, presumably by non-oxidative means, without replacement of glucose due to reduced CBF.

Distinct connectivity patterns in human medial parietal cortices: Evidence from standardized connectivity map using cortico-cortical evoked potential.

The medial parietal cortices are components of the default mode network (DMN), which are active in the resting state. The medial parietal cortices include the precuneus and the dorsal posterior cingulate cortex (dPCC). Few studies have mentioned differences in the connectivity in the medial parietal cortices, and these differences have not yet been precisely elucidated. Electrophysiological connectivity is essential for understanding cortical function or functional differences. Since little is known about electrophysiological connections from the medial parietal cortices in humans, we evaluated distinct connectivity patterns in the medial parietal cortices by constructing a standardized connectivity map using cortico-cortical evoked potential (CCEP). This study included nine patients with partial epilepsy or a brain tumor who underwent chronic intracranial electrode placement covering the medial parietal cortices. Single-pulse electrical stimuli were delivered to the medial parietal cortices (38 pairs of electrodes). Responses were standardized using the z-score of the baseline activity, and a response density map was constructed in the Montreal Neurological Institutes (MNI) space. The precuneus tended to connect with the inferior parietal lobule (IPL), the occipital cortex, superior parietal lobule (SPL), and the dorsal premotor area (PMd) (the four most active regions, in descending order), while the dPCC tended to connect to the middle cingulate cortex, SPL, precuneus, and IPL. The connectivity pattern differs significantly between the precuneus and dPCC stimulation (p<0.05). Regarding each part of the medial parietal cortices, the distributions of parts of CCEP responses resembled those of the functional connectivity database. Based on how the dPCC was connected to the medial frontal area, SPL, and IPL, its connectivity pattern could not be explained by DMN alone, but suggested a mixture of DMN and the frontoparietal cognitive network. These findings improve our understanding of the connectivity profile within the medial parietal cortices. The electrophysiological connectivity is the basis of propagation of electrical activities in patients with epilepsy. In addition, it helps us to better understand the epileptic network arising from the medial parietal cortices.

Self-regulation of the posterior cingulate cortex with real-time fMRI neurofeedback augmented mindfulness training in healthy adolescents: A nonrandomized feasibility study.

Mindfulness training (MT) promotes the development of one's ability to observe and attend to internal and external experiences with objectivity and nonjudgment with evidence to improve psychological well-being. Real-time functional MRI neurofeedback (rtfMRI-nf) is a noninvasive method of modulating activity of a brain region or circuit. The posterior cingulate cortex (PCC) has been hypothesized to be an important hub instantiating a mindful state. This nonrandomized, single-arm study examined the feasibility and tolerability of training typically developing adolescents to self-regulate the posterior cingulate cortex (PCC) using rtfMRI-nf during MT. Thirty-four adolescents (mean age: 15 years; 14 females) completed the neurofeedback augmented mindfulness training task, including Focus-on-Breath (MT), Describe (self-referential thinking), and Rest conditions, across three neurofeedback and two non-neurofeedback runs (Observe, Transfer). Self-report assessments demonstrated the feasibility and tolerability of the task. Neurofeedback runs differed significantly from non-neurofeedback runs for the Focus-on-Breath versus Describe contrast, characterized by decreased activity in the PCC during the Focus-on-Breath condition (z = -2.38 to -6.27). MT neurofeedback neural representation further involved the medial prefrontal cortex, anterior cingulate cortex, dorsolateral prefrontal cortex, posterior insula, hippocampus, and amygdala. State awareness of physical sensations increased following rtfMRI-nf and was maintained at 1-week follow-up (Cohens' d = 0.69). Findings demonstrate feasibility and tolerability of rtfMRI-nf in healthy adolescents, replicates the role of PCC in MT, and demonstrate a potential neuromodulatory mechanism to leverage and streamline the learning of mindfulness practice. ( ClinicalTrials.gov identifier #NCT04053582; August 12, 2019).

The impact of smoking status on cognition and brain morphology in schizophrenia spectrum disorders.

BACKGROUND: Cigarette smoking is associated with worse cognition and decreased cortical volume and thickness in healthy cohorts. Chronic cigarette smoking is prevalent in schizophrenia spectrum disorders (SSD), but the effects of smoking status on the brain and cognition in SSD are not clear. This study aimed to understand whether cognitive performance and brain morphology differed between smoking and non-smoking individuals with SSD compared to healthy controls. METHODS: Data were obtained from the Australian Schizophrenia Research Bank. Cognitive functioning was measured in 299 controls and 455 SSD patients. Cortical volume, thickness and surface area data were analysed from T1-weighted structural scans obtained in a subset of the sample (n = 82 controls, n = 201 SSD). Associations between smoking status (cigarette smoker/non-smoker), cognition and brain morphology were tested using analyses of covariance, including diagnosis as a moderator. RESULTS: No smoking by diagnosis interactions were evident, and no significant differences were revealed between smokers and non-smokers across any of the variables measured, with the exception of a significantly thinner left posterior cingulate in smokers compared to non-smokers. Several main effects of smoking in the cognitive, volume and thickness analyses were initially significant but did not survive false discovery rate (FDR) correction. CONCLUSIONS: Despite the general absence of significant FDR-corrected findings, trend-level effects suggest the possibility that subtle smoking-related effects exist but were not uncovered due to low statistical power. An investigation of this topic is encouraged to confirm and expand on our findings.

Poor sleep accelerates hippocampal and posterior cingulate volume loss in cognitively normal healthy older adults.

Poor sleep quality is a known risk factor for Alzheimer's disease. This longitudinal imaging study aimed to determine the acceleration in the rates of tissue loss in cognitively critical brain regions due to poor sleep in healthy elderly individuals. Cognitively-normal healthy individuals, aged ≥60 years, reported Pittsburgh Sleep Quality Index (PSQI) and underwent baseline and 2-year follow-up magnetic resonance imaging brain scans. The links between self-reported sleep quality, rates of tissue loss in cognitively-critical brain regions, and white matter hyperintensity load were assessed. A total of 48 subjects were classified into normal (n = 23; PSQI score <5) and poor sleepers (n = 25; PSQI score ≥5). The two groups were not significantly different in terms of age, gender, years of education, ethnicity, handedness, body mass index, and cognitive performance. Compared to normal sleepers, poor sleepers exhibited much faster rates of volume loss, over threefold in the right hippocampus and fivefold in the right posterior cingulate over 2 years. In contrast, there were no significant differences in the rates of volume loss in the cerebral and cerebellar grey and white matter between the two groups. Rates of volume loss in the right posterior cingulate were negatively associated with global PSQI scores. Poor sleep significantly accelerates volume loss in the right hippocampus and the right posterior cingulate cortex. These findings demonstrate that self-reported sleep quality explains inter-individual differences in the rates of volume loss in cognitively-critical brain regions in healthy older adults and provide a strong impetus to offer sleep interventions to cognitively normal older adults who are poor sleepers.

Going round in circles-The Papez circuit in Alzheimer's disease.

The hippocampus is regarded as the pivotal structure for episodic memory symptoms associated with Alzheimer's disease (AD) pathophysiology. However, what is often overlooked is that the hippocampus is 'only' one part of a network of memory critical regions, the Papez circuit. Other Papez circuit regions are often regarded as less relevant for AD as they are thought to sit 'downstream' of the hippocampus. However, this notion is oversimplistic, and increasing evidence suggests that other Papez regions might be affected before or concurrently with the hippocampus. In addition, AD research has mostly focused on episodic memory deficits, whereas spatial navigation processes are also subserved by the Papez circuit with increasing evidence supporting its valuable potential as a diagnostic measure of incipient AD pathophysiology. In the current review, we take a step forward analysing recent evidence on the structural and functional integrity of the Papez circuit across AD disease stages. Specifically, we will review the integrity of specific Papez regions from at-genetic-risk (APOE4 carriers), to mild cognitive impairment (MCI), to dementia stage of sporadic AD and autosomal dominant AD (ADAD). We related those changes to episodic memory and spatial navigation/orientation deficits in AD. Finally, we provide an overview of how the Papez circuit is affected in AD diseases and their specific symptomology contributions. This overview strengthened the need for moving away from a hippocampal-centric view to a network approach on how the whole Papez circuit is affected in AD and contributes to its symptomology, informing future research and clinical approaches.

Impaired posterior cingulate cortex-parahippocampus connectivity is associated with episodic memory retrieval problems in amnestic mild cognitive impairment.

Episodic memory retention and retrieval decline are the most common impairments observed in amnestic mild cognitive impairment (aMCI) patients who progress to Alzheimer's disease (AD). Clinical electroencephalography research shows that patients with dementia due to AD exhibit a slowing of neural electrical activity in the parietal cortex. Memory research has further suggested that successful memory performance is associated with changes in a posterior cingulate-parahippocampal cortical network together with increased θ-γ oscillatory coupling, where θ oscillations act as carrier waves for γ oscillations, which contain the actual information. However, the neurophysiological link between the memory research and clinical studies investigating aMCI and AD is lacking. In this study, we look at brain activity in aMCI and how it relates to memory performance. We demonstrate decreased γ power in the posterior cingulate cortex and the left and right parahippocampus in aMCI patients in comparison to control participants. This goes together with reduced θ coherence between the posterior cingulate cortex and parahippocampus associated with altered memory performance aMCI patients in comparison to control participants. In addition, comparing patients with aMCI to control participants reveals an effect for θ-γ coupling for the posterior cingulate cortex, and the left and right parahippocampus. Taken together, our results show that parahippocampus and posterior cingulate cortex interact via θ-γ coupling, which is associated with memory recollection and is altered in aMCI patients, offering a potential candidate mechanism for memory decline in aMCI.