Multiple Brain Areas Research Articles

MAP2 immunoreactivity deficit is conserved across the cerebral cortex within individuals with schizophrenia

Several postmortem studies have reported lower levels of immunoreactivity (IR) for microtubule-associated protein 2 (MAP2) in several cortical regions of individuals with schizophrenia (SZ). However, whether this effect is conserved across multiple brain areas within an individual with SZ or if it is regionally-specific remains unclear. We characterized patterns of MAP2-IR across three cortical regions at different levels of the rostral-caudal axis within individual subjects with and without SZ. MAP2-IR levels were measured in deep layer 3 of dorsolateral prefrontal cortex (DLPFC), lateral intraparietal cortex (LIP), and primary visual cortex (V1). Postmortem tissue containing each cortical region was derived from 20 pairs of SZ subjects and nonpsychiatric comparison (NPC) subjects matched perfectly for sex, and as closely as possible for age and postmortem interval. MAP2-IR was assessed by quantitative fluorescence microscopy. We observed significantly lower levels of MAP2-IR in SZ subjects relative to NPC subjects, without a significant region by diagnosis interaction. Logs of the within-pair ratios (SZ:NPC) of MAP2-IR were significantly correlated across the three regions. These findings demonstrate that MAP2-IR deficits in SZ are consistent across three neocortical regions within individual subjects. This pattern of MAP2-IR deficit has implications for therapeutic development and future investigations of MAP2 pathology in SZ.

A Whole-Body Sensory-Motor Gradient is Revealed in the Medial Wall of the Parietal Lobe.

In 1954, Penfield and Jasper's findings based on electric stimulation of epileptic patients led them to hypothesize that a sensory representation of the body should be found in the precuneus. They termed this representation the "supplementary sensory" area and emphasized that the exact form of this homunculus could not be specified on the basis of their results. In the decades that followed, their prediction was neglected. The precuneus was found to be involved in numerous motor, cognitive and visual processes, but no work was done on its somatotopic organization. Here, we used a periodic experimental design in which 16 human subjects (eight women) moved 20 body parts to investigate the possible body part topography of the precuneus. We found an anterior-to-posterior, dorsal-to-ventral, toes-to-tongue gradient in a mirror orientation to the SMA. When inspecting body-part-specific functional connectivity, we found differential connectivity patterns for the different body parts to the primary and secondary motor areas and parietal and visual areas, and a shared connectivity to the extrastriate body area, another topographically organized area. We suggest that a whole-body gradient can be found in the precuneus and is connected to multiple brain areas with different connectivity for different body parts. Its exact role and relations to the other known functions of the precuneus such as self-processing, motor imagery, reaching, visuomotor and other body-mind functions should be investigated.SIGNIFICANCE STATEMENT Using fMRI, as well as sensitive spectral analysis, we found a new homunculus in the precuneus: an anterior-to-posterior, dorsal-to-ventral, toes-to-tongue somatotopic gradient in a mirror orientation to the SMA. When inspecting body-part-specific functional connectivity, we found differential connectivity patterns for the different body parts to the primary and secondary motor areas, parietal and visual areas, and a shared connectivity to the extrastriate body area, another topographically organized area. We suggest that a whole-body gradient can be found in the precuneus and is connected to multiple brain areas in a body-part-specific manner.

Microglial Depletion Causes Region-Specific Changes to Developmental Neuronal Cell Death in the Mouse Brain.

Developmental neuronal cell death has been characterized as a cell autonomous "suicide" program, but recent findings suggest that microglia play an active role in determining the survival of developing neurons. Results have been contradictory, however, with some studies concluding that microglia promote cell death, while others report that microglia are neuroprotective. Here, we depleted microglia throughout the newborn mouse brain using intracerebroventricular injections of clodronate liposomes, and examined effects on naturally occurring cell death across multiple brain areas. Microglial density varied significantly by brain region, and clodronate liposome treatment at birth reduced the number of microglia in all regions examined. The effect of microglia reduction on cell death, however, varied by region: the number of dying cells was reduced in the medial septum and medial amygdala in clodronate treated animals, but was increased in the oriens layer of the hippocampus, and unchanged in several other brain regions. In most brain regions, the average size of microglia was greater in microglia-depleted than in control animals, suggesting that the remaining microglia compensate to some extent for a reduction in microglial number. The hippocampal oriens was exceptional in this regard, in that microglial size was reduced following treatment with clodronate. Microglia produce cytokines which mediate many of their effects, and we found higher expression of inflammatory cytokines in the hippocampus than in the septum, independent of clodronate treatment. Thus, microglial depletion has opposite effects on cell death in different brain regions of the newborn brain, which may be related to regional heterogeneity in microglia.

GABA neurons in the ventral tegmental area regulate non-rapid eye movement sleep in mice

Sleep/wakefulness cycle is regulated by coordinated interactions between sleep- and wakefulness-regulating neural circuitry. However, the detailed mechanism is far from understood. Here, we found that glutamic acid decarboxylase 67-positive GABAergic neurons in the ventral tegmental area (VTAGad67+) are a key regulator of non-rapid eye movement (NREM) sleep in mice. VTAGad67+ project to multiple brain areas implicated in sleep/wakefulness regulation such as the lateral hypothalamus (LH). Chemogenetic activation of VTAGad67+ promoted NREM sleep with higher delta power whereas optogenetic inhibition of these induced prompt arousal from NREM sleep, even under highly somnolescent conditions, but not from REM sleep. VTAGad67+ showed the highest activity in NREM sleep and the lowest activity in REM sleep. Moreover, VTAGad67+ directly innervated and inhibited wake-promoting orexin/hypocretin neurons by releasing GABA. As such, optogenetic activation of VTAGad67+ terminals in the LH promoted NREM sleep. Taken together, we revealed that VTAGad67+ play an important role in the regulation of NREM sleep.

Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice

BackgroundXenon is a noble gas with neuroprotective properties that can improve short and long-term outcomes in young adult mice after controlled cortical impact. This follow-up study investigates the effects of xenon on very long-term outcomes and survival. MethodsC57BL/6N young adult male mice (n=72) received single controlled cortical impact or sham surgery and were treated with either xenon (75% Xe:25% O2) or control gas (75% N2:25% O2). Outcomes measured were: (i) 24 h lesion volume and neurological outcome score; (ii) contextual fear conditioning at 2 weeks and 20 months; (iii) corpus callosum white matter quantification; (iv) immunohistological assessment of neuroinflammation and neuronal loss; and (v) long-term survival. ResultsXenon treatment significantly reduced secondary injury (P<0.05), improved short-term vestibulomotor function (P<0.01), and prevented development of very late-onset traumatic brain injury (TBI)-related memory deficits. Xenon treatment reduced white matter loss in the contralateral corpus callosum and neuronal loss in the contralateral hippocampal CA1 and dentate gyrus areas at 20 months. Xenon's long-term neuroprotective effects were associated with a significant (P<0.05) reduction in neuroinflammation in multiple brain areas involved in associative memory, including reduction in reactive astrogliosis and microglial cell proliferation. Survival was improved significantly (P<0.05) in xenon-treated animals compared with untreated animals up to 12 months after injury. ConclusionsXenon treatment after TBI results in very long-term improvements in clinically relevant outcomes and survival. Our findings support the idea that xenon treatment shortly after TBI may have long-term benefits in the treatment of brain trauma patients.

Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection

Neuronal and synaptic loss is characteristic in many neurodegenerative diseases, such as frontotemporal dementia and Alzheimer's disease. Recently, we showed that inducing gamma oscillations with visual stimulation (gamma entrainment using sensory stimuli, or GENUS) reduced amyloid plaques and phosphorylated tau in multiple mouse models. Whether GENUS can affect neurodegeneration or cognitive performance remains unknown. Here, we demonstrate that GENUS can entrain gamma oscillations in the visual cortex, hippocampus, and prefrontal cortex in Tau P301S and CK-p25 mouse models of neurodegeneration. Tau P301S and CK-p25 mice subjected to chronic, daily GENUS from the early stages of neurodegeneration showed a preservation of neuronal and synaptic density across multiple brain areas and modified cognitive performance. Our transcriptomic and phosphoproteomic data suggest that chronic GENUS shifts neurons to a less degenerative state, improving synaptic function, enhancing neuroprotective factors, and reducing DNA damage in neurons while also reducing inflammatory response in microglia.

Long-range functional coupling predicts performance: Oscillatory EEG networks in multisensory processing

The integration of sensory signals from different modalities requires flexible interaction of remote brain areas. One candidate mechanism to establish communication in the brain is transient synchronization of oscillatory neural signals. Although there is abundant evidence for the involvement of cortical oscillations in brain functions based on the analysis of local power, assessment of the phase dynamics among spatially distributed neuronal populations and their relevance for behavior is still sparse. In the present study, we investigated the interaction between remote brain areas by analyzing high-density electroencephalogram (EEG) data obtained from human participants engaged in a visuotactile pattern matching task. We deployed an approach for purely data-driven clustering of neuronal phase coupling in source space, which allowed imaging of large-scale functional networks in space, time and frequency without defining a priori constraints. Based on the phase coupling results, we further explored how brain areas interacted across frequencies by computing phase-amplitude coupling. Several networks of interacting sources were identified with our approach, synchronizing their activity within and across the theta (∼5 Hz), alpha (∼10 Hz), and beta (∼20 Hz) frequency bands and involving multiple brain areas that have previously been associated with attention and motor control. We demonstrate the functional relevance of these networks by showing that phase delays – in contrast to spectral power – were predictive of task performance. The data-driven analysis approach employed in the current study allowed an unbiased examination of functional brain networks based on EEG source level connectivity data. Showcased for multisensory processing, our results provide evidence that large-scale neuronal coupling is vital to long-range communication in the human brain and relevant for the behavioral outcome in a cognitive task.

Morphine-Induced Dendritic Spine Remodeling in Rat Nucleus Accumbens Is Corticosterone Dependent.

BackgroundChronic morphine treatments produce important morphological changes in multiple brain areas including the nucleus accumbens.MethodsIn this study, we have investigated the effect of chronic morphine treatment at a relatively low dose on the morphology of medium spiny neurons in the core and shell of the nucleus accumbens in rats 1 day after the last injection of a chronic morphine treatment (5 mg/kg once per day for 14 days). Medium spiny neurons were labeled with 1,1’ dioctadecyl-3,3,3’,3’-tetramethylindocarbocyanine perchlorate crystal and analyzed by confocal laser-scanning microscope.ResultsOur results show an increase of thin spines and a decrease of stubby spines specifically in the shell of morphine-treated rats compared with control. Since morphine-treated rats also presented an elevation of corticosterone level in plasma, we explored whether spine alterations induced by morphine treatment in the nucleus accumbens could be affected by the depletion of the hormone. Thus, bilaterally adrenalectomized rats were treated with morphine in the same conditions. No more alteration in stubby spines in the shell was detected in morphine-treated rats with a depletion of corticosterone, while a significant increase was observed in mushroom spines in the shell and stubby spines in the core. Regarding the thin spines, the increase observed with morphine compared with saline was lower in adrenalectomized rats than in nonadrenalectomized animals.ConclusionThese results indicate that dendritic spine remodeling in nucleus accumbens following chronic morphine treatment at relatively low doses is dependent on corticosterone levels.

Corticobasal syndrome: neuroimaging and neurophysiological advances.

Corticobasal degeneration (CBD) is a neurodegenerative condition characterized by 4R tau protein deposition in several brain regions that clinically manifests itself as a heterogeneous atypical parkinsonism typically expressed in adulthood. The prototypical clinical phenotype of CBD is corticobasal syndrome (CBS). Important insights into the pathophysiological mechanisms underlying motor and higher cortical symptoms in CBS have been gained by using advanced neuroimaging and neurophysiological techniques. Structural and functional neuroimaging studies often show asymmetric cortical and subcortical abnormalities, mainly involving perirolandic and parietal regions and basal ganglia structures. Neurophysiological investigations including electroencephalography and somatosensory evoked potentials provide useful information on the origin of myoclonus and on cortical sensory loss. Transcranial magnetic stimulation demonstrates heterogeneous and asymmetric changes in the excitability and plasticity of primary motor cortex and abnormal hemispheric connectivity. Neuroimaging and neurophysiological abnormalities in multiple brain areas reflect asymmetric neurodegeneration, leading to asymmetric motor and higher cortical symptoms in CBS.

Multi-sensory Gamma Stimulation Ameliorates Alzheimer’s-Associated Pathology and Improves Cognition

We previously reported that inducing gamma oscillations with a non-invasive light flicker (gamma entrainment using sensory stimulus or GENUS) impacted pathology in the visual cortex of Alzheimer's disease mouse models. Here, we designed auditory tone stimulation that drove gamma frequency neural activity in auditory cortex (AC) and hippocampal CA1. Seven days of auditory GENUS improved spatial and recognition memory and reduced amyloid in AC and hippocampus of 5XFAD mice. Changes in activation responses were evident in microglia, astrocytes, and vasculature. Auditory GENUS also reduced phosphorylated tau in the P301S tauopathy model. Furthermore, combined auditory and visual GENUS, but not either alone, produced microglial-clustering responses, and decreased amyloid in medial prefrontal cortex. Whole brain analysis using SHIELD revealed widespread reduction of amyloid plaques throughout neocortex after multi-sensory GENUS. Thus, GENUS can be achieved through multiple sensory modalities with wide-ranging effects across multiple brain areas to improve cognitive function.

Characteristics of impulsiveness and aggressiveness in patients with hepatolenticular degeneration and its relationship with brain structure

Objective To investigate the impulsivity and aggressiveness characteristics of patients with hepatolenticular degeneration(HLD) and its relationship with brain structure. Methods The Chinese version of the Barratt impulsiveness scale, 11 version(BIS-11-C) and Buss-Perry aggression questionnaire(BPAQ) were assessed in 78 patients with hepatolenticular degeneration(HLD group) and 86 normal adults(health control group). HLD patients were examined by 3.0T magnetic resonance imaging (MRI). The differences in impulsivity and aggressiveness of the two groups were compared, and the relationship was analyzed between impulsivity, aggressiveness and different brain structures in patients with HLD. Results The total impulsive score, unplanned factor score, the total aggressive score and anger factor score of patients with cerebral HLD(61.74±9.82, 26.08±5.06, 82.71±15.92, 20.06±5.74, respectively) were higher than those in patients with hepatic HLD (56.73±7.11, 23.02±4.20, 72.84±11.15, 16.64±5.01, respectively), and health control group(52.19±7.53, 21.50±3.93, 64.64±9.83, 14.27±4.38, respectively), and the differences were significant (F=3.193, 4.646, 11.830, 8.270, all P<0.05). Total impulsive score was positively correlated with aggressive score and physical aggression in HLD group(r=0.299, 0.290, both P<0.05). Unplanned score was positively correlated with aggressive total score (r=0.324) and physical aggression (r=0.320) in HLD group (P<0.05). Frontal lobe injury was the influencing factor of total impulsive score(B=10.263, 95%CI=0.467-19.946, P=0.008), attention score(B=2.837, 95%CI=0.382-5.600, P=0.010) and unplanned factor score(B=3.977, 95%CI=0.848-8.502, P=0.046). Thalamus injury was the influencing factor of aggressive total score and its factor score.Caudate nucleus injury was the influencing factor of aggressive total score (B=10.030, 95% CI=3.351-18.039, P=0.017) and physical aggression score (B=4.432, 95% CI=1.193-7.729, P=0.016). Conclusion Patients with HLD have higher impulsive and aggressive tendencies, which are mainly manifested in unplanned impulsive and anger tendencies.Brain injury may be an important factor affecting impulsiveness and aggression in patients with HLD.Impulsiveness is related with frontal lobe injury and aggression to thalamus and caudate nucleus injury.Impulsiveness and aggressiveness in patients with HLD are not caused by damage to isolated brain areas, but are related to damage to multiple brain areas. Key words: Hepatolenticular degeneration; Wilson's disease; Impulsivity; Aggressiveness; Brain structure damage

Biologically Realistic Mean-Field Models of Conductance-Based Networks of Spiking Neurons with Adaptation.

Accurate population models are needed to build very large-scale neural models, but their derivation is difficult for realistic networks of neurons, in particular when nonlinear properties are involved, such as conductance-based interactions and spike-frequency adaptation. Here, we consider such models based on networks of adaptive exponential integrate-and-fire excitatory and inhibitory neurons. Using a master equation formalism, we derive a mean-field model of such networks and compare it to the full network dynamics. The mean-field model is capable of correctly predicting the average spontaneous activity levels in asynchronous irregular regimes similar to in vivo activity. It also captures the transient temporal response of the network to complex external inputs. Finally, the mean-field model is also able to quantitatively describe regimes where high- and low-activity states alternate (up-down state dynamics), leading to slow oscillations. We conclude that such mean-field models are biologically realistic in the sense that they can capture both spontaneous and evoked activity, and they naturally appear as candidates to build very large-scale models involving multiple brain areas.

Monitoring deep brain stimulation by measuring regional brain oxygen responses in freely moving mice

BackgroundTranslational studies investigating the effects of deep brain stimulation (DBS) on brain function up to now mainly relied on BOLD responses measured with fMRI. However, fMRI studies in rodents face technical and practical limitations (e.g., immobilization, sedation or anesthesia, spatial and temporal resolution of data). Direct measurement of oxygen concentration in the brain using electrochemical sensors is a promising alternative to the use of fMRI. Here, we tested for the first time if such measurements can be combined with DBS. New methodWe combined bilateral DBS in the internal capsule (IC-DBS) with simultaneous amperometric measurements of oxygen in the medial prefrontal cortex (prelimbic area) and striatum of freely moving mice. Using a two-day within-animal experimental design, we tested the effects of DBS on baseline oxygen concentrations, and on novelty- and restraint-induced increases in oxygen concentration. ResultsBasal oxygen levels were stable across the daily sampling periods. Exposure to novelty and immobilization reproducibly increased oxygen concentrations in both areas. IC-DBS did not significantly alter basal oxygen, but reduced the novelty-induced increase in the striatum. Comparison with existing method(s)Amperometric detection of brain oxygen concentration with high temporal and spatial resolution can be performed in a number of key brain areas to study the effects of DBS in animal models of disease. The method is easily implemented and does not require expensive equipment or complicated data analysis processes. ConclusionsDirect and simultaneous measurement of brain oxygen concentration in multiple brain areas can be used to study the effects of bilateral DBS neuromodulation on brain activity in freely moving mice.

VGLUT3 gates psychomotor effects induced by amphetamine.

Several subtypes of modulatory neurons co-express vesicular glutamate transporters (VGLUTs) in addition to their cognate vesicular transporters. These neurons are believed to establish new forms of neuronal communication. The atypical VGLUT3 is of particular interest since in the striatum this subtype is found in tonically active cholinergic interneurons (TANs) and in a subset of 5-HT fibers. The striatum plays a major role in psychomotor effects induced by amphetamine. Whether and how VGLUT3-operated glutamate/ACh or glutamate/5HT co-transmissions modulates psychostimulants-induced maladaptive behaviors is still unknown. Here, we investigate the involvement of VGLUT3 and glutamate co-transmission in amphetamine-induced psychomotor effects and stereotypies. Taking advantage of constitutive and cell-type specific VGLUT3-deficient mouse lines, we tackled the hypothesis that VGLUT3 could gate psychomotor effects (locomotor activity and stereotypies) induced by acute or chronic administration of amphetamine. Interestingly, VGLUT3-null mice demonstrated blunted amphetamine-induced stereotypies as well as reduced striatal ∆FosB expression. VGLUT3-positive varicosities within the striatum arise in part from 5HT neurons. We tested the involvement of VGLUT3 deletion in serotoninergic neurons in amphetamine-induced stereotypies. Mice lacking VGLUT3 specifically in 5HT fibers showed no alteration to amphetamine sensitivity. In contrast, specific deletion of VGLUT3 in cholinergic neurons partially phenocopied the effects observed in the constitutive knock-out mice. Our results show that constitutive deletion of VGLUT3 modulates acute and chronic locomotor effects induced by amphetamine. They point to the fact that the expression of VGLUT3 in multiple brain areas is pivotal in gating amphetamine-induced psychomotor adaptations. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.

Transsacadic Information and Corollary Discharge in Local Field Potentials of Macaque V1.

Approximately three times per second, human visual perception is interrupted by a saccadic eye movement. In addition to taking the eyes to a new location, several lines of evidence suggest that the saccades play multiple roles in visual perception. Indeed, it may be crucial that visual processing is informed about movements of the eyes in order to analyze visual input distinctly and efficiently on each fixation and preserve stable visual perception of the world across saccades. A variety of studies has demonstrated that activity in multiple brain areas is modulated by saccades. The hypothesis tested here is that these signals carry significant information that could be used in visual processing. To test this hypothesis, local field potentials (LFPs) were simultaneously recorded from multiple electrodes in macaque primary visual cortex (V1); support vector machines (SVMs) were used to classify the peri-saccadic LFPs. We find that LFPs in area V1 carry information that can be used to distinguish neural activity associated with fixations from saccades, precisely estimate the onset time of fixations, and reliably infer the directions of saccades. This information may be used by the brain in processes including visual stability, saccadic suppression, receptive field (RF) remapping, fixation amplification, and trans-saccadic visual perception.

The Dynamic Brain Networks of Motor Imagery: Time-Varying Causality Analysis of Scalp EEG.

Motor imagery (MI) requires subjects to visualize the requested motor behaviors, which involves a large-scale network that spans multiple brain areas. The corresponding cortical activity reflected on the scalp is characterized by event-related desynchronization (ERD) and then by event-related synchronization (ERS). However, the network mechanisms that account for the dynamic information processing of MI during the ERD and ERS periods remain unknown. Here, we combined ERD/ERS analysis with the dynamic networks in different MI stages (i.e. motor preparation, ERD and ERS) to probe the dynamic processing of MI information. Our results show that specific dynamic network structures correspond to the ERD/ERS evolution patterns. Specifically, ERD mainly shows the contralateral networks, while ERS has the symmetric networks. Moreover, different dynamic network patterns are also revealed between the two types of MIs, in which the left-hand MIs exhibit a relatively less sustained contralateral network, which may be the network mechanism that accounts for the bilateral ERD/ERS observed for the left-hand MIs. Similar to the network topologies, the three MI stages also appear to be characterized by different network properties. The above findings all demonstrate that different MI stages that involve specific brain networks for dynamically processing the MI information.

Understanding Sensory Information Processing Through Simultaneous Multi-area Population Recordings.

The goal of sensory neuroscience is to understand how the brain creates its myriad of representations of the world, and uses these representations to produce perception and behavior. Circuits of neurons in spatially segregated regions of brain tissue have distinct functional specializations, and these regions are connected to form a functional processing hierarchy. Advances in technology for recording neuronal activity from multiple sites in multiple cortical areas mean that we are now able to collect data that reflects how information is transformed within and between connected members of this hierarchy. This advance is an important step in understanding the brain because, after the sensory organs have transduced a physical signal, every processing stage takes the activity of other neurons as its input, not measurements of the physical world. However, as we explore the potential of studying how populations of neurons in multiple areas respond in concert, we must also expand both the analytical tools that we use to make sense of these data and the scope of the theories that we attempt to define. In this article, we present an overview of some of the most promising analytical approaches for making inferences from population recordings in multiple brain areas, such as dimensionality reduction and measuring changes in correlated variability, and examine how they may be used to address longstanding questions in sensory neuroscience.

Altered Regional Cerebral Blood Flow Associated with Mood and Sleep in Shift Workers: Cerebral Perfusion Magnetic Resonance Imaging Study.

Background and PurposeShift work disrupts the body's circadian rhythms and increases the risk of health problems. Despite evidence of neuropsychological disturbances in shift workers (SW), the brain functional status as measured by brain perfusion in chronic shift work has not been evaluated previously. We investigated the regional cerebral blood flow (rCBF) in SW using perfusion MRI (pMRI) and evaluated the relationships between altered rCBF and sleep, mood, psychometric measures, and quality of life.MethodsFifteen rotational SW and 15 day workers (DW) were enrolled. The participants were all female nurses working at a university-affiliated hospital. During 2 weeks of actigraphy they underwent pMRI scanning and psychometric testing on the last day immediately after working. Demographic characteristics, insomnia, daytime sleepiness, and mood were compared between the groups.ResultsThe participants were aged 35.3±2.9 years (mean±SD) and had been performing their current work for more than 2 years. The demographic characteristics did not differ between SW and DW, but the levels of insomnia, anxiety, depression, and hyperactivity-restlessness in psychometric measures were higher in SW than in DW. Cerebral perfusion in SW was significantly decreased in the cuneus, fusiform/parahippocampal gyri, and cerebellum of the right hemisphere, while it was increased in the inferior occipital gyrus of the left hemisphere. Perfusion changes in SW were significantly correlated with depression and insomnia severity. The onset and duration irregularity of sleep among SW were related to insomnia, mood, hyperactivity/ restlessness, and quality of life.ConclusionsSW experience considerably more insomnia and mood disturbances than do DW, and this is significantly related to perfusion changes in multiple brain areas.

Flexible network community organization during the encoding and retrieval of spatiotemporal episodic memories.

Memory encoding and retrieval involve distinct interactions between multiple brain areas, yet the flexible structure of corresponding large-scale networks during such memory processing remains unclear. Using functional magnetic resonance imaging, we employed a spatiotemporal encoding and retrieval task, detecting functional community structure across the multiple components of our task. Consistent with past work, we identified a set of stable subnetworks, mostly belonging to primary motor and sensory cortices but also identified a subset of flexible hubs, mostly belonging to higher association areas. These “mover” hubs changed connectivity patterns across spatial and temporal memory encoding and retrieval, engaging in an integrative role within the network. Global encoding network and subnetwork dissimilarity predicted retrieval performance. Together, our findings emphasize the importance of flexible network allegiance among some hubs and the importance of network reconfiguration to human episodic memory.

Involvement of CA1 GABAA Receptors in Ketamine-Induced Impairment of Spatial and Non-Spatial Novelty Detection in Mice

Inhibitory GABAergic and excitatory glutamatergic neurons from multiple brain areas, send fibers to the hippocampal CA1 region. NMDA receptors have been identified as important compoents of the brain system underlying memory formation, which that through an increase in glutamate-mediated neurotransmission. Ketamine and other NMDA receptor antagonists produce deficits in cognitive tasks, including both spatial and non-spatial memory. In the current study, we tested whether the activation or inhibition of GABAA receptors in CA1 hippocampal of mice has an impact on ketamine (NMDA antagonist) induced spatial and non-spatial novelty detection deficits. Adult male mice weighing between 25–30 g were used. The open-field method was used to evaluate spatial and non-spatial memory information. Data obtained from the present study revealed that an intra-CA1 injection with a sub-threshold dose the GABAA receptor antagonist bicuculline (0.0625 µg mouse) disrupted spatial memory but restored non-spatial memory induced by lower and higher doses of ketamine (0.05 and 0.01 mg/kg) respectively. Meanwhile, the co-administration of the intra-CA1 injection with a sub-threshold dose of muscimol (GABAA receptor agonist at 0.25 µg/mouse) and a lower dose of ketamine could only impair the ability of non-spatial change detection but could not alter spatial novelty. In conclusion, ketamine (which contributes to the impairment of memory trace stored in the hippocampus) may be generated from GABAA receptors of CA1 neurons and their blockade could prevent these effects.