The Biological Mechanism of Maternal Depression’s Negative Influences on Offspring Development: A Review

Maternal depression is a prevalent disorder among mothers: nearly 20% of women have experienced different levels of depressive symptoms during motherhood. The symptoms usually disappear by three years after their children were born, but some women experience them chronically. Maternal depression has been researched in terms of its negative influence on offspring since the 1960s. Children of chronically depressed mothers show delays in cognitive, emotional, and behavioral development. Moreover, they may even face mental health challenges themselves. How does maternal depression influence offspring? Previous studies have focused on the behaviors of mothers and found that mothers with depression interact with their children in a less engaging way. Recently, more researchers started to pay attention to the biological mechanism of this maternal depression’s negative influence. Cortisol, a hormone associated with stress, is regarded as a potential pathway of the transgenerational transmission of depression. Mothers with prenatal depression have elevated cortisol level during pregnancy, which is passed down to their children. After they are born, children of depressed mothers react to stress with more dramatic changes in cortisol level and compromised stress-coping abilities. Moreover, prenatal maternal depression also seems to shape the functional connectivity of amygdala, a brain area related to stress and emotions. For life situations like schooling, competing with peers or making significant decisions, children with decreased or abnormal stress-coping abilities will be in disadvantageous positions. Attenuated stress coping abilities brought by hormonal and neural changes may be a biological mechanism for children’s lower performance in cognitive and behavioral tasks.

Functional Changes in Brain Activity Using Hypnosis: A Systematic Review

Hypnosis has proven a powerful method in indications such as pain control and anxiety reduction. As recently discussed, it has been yielding increased attention from medical/dental perspectives. This systematic review (PROSPERO-registration-ID-CRD42021259187) aimed to critically evaluate and discuss functional changes in brain activity using hypnosis by means of different imaging techniques. Randomized controlled trials, cohort, comparative, cross-sectional, evaluation and validation studies from three databases—Cochrane, Embase and Medline via PubMed from January 1979 to August 2021—were reviewed using an ad hoc prepared search string and following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. A total of 10404 articles were identified, 1194 duplicates were removed and 9190 papers were discarded after consulting article titles/abstracts. Ultimately, 20 papers were assessed for eligibility, and 20 papers were included after a hand search (ntotal = 40). Despite a broad heterogenicity of included studies, evidence of functional changes in brain activity using hypnosis was identified. Electromyography (EMG) startle amplitudes result in greater activity in the frontal brain area; amplitudes using Somatosensory Event-Related Potentials (SERPs) showed similar results. Electroencephalography (EEG) oscillations of θ activity are positively associated with response to hypnosis. EEG results showed greater amplitudes for highly hypnotizable subjects over the left hemisphere. Less activity during hypnosis was observed in the insula and anterior cingulate cortex (ACC).

Dependence of Working Memory on Coordinated Activity Across Brain Areas

Neural signatures of working memory (WM) have been reported in numerous brain areas, suggesting a distributed neural substrate for memory maintenance. In the current manuscript we provide an updated review of the literature focusing on intracranial neurophysiological recordings during WM in primates. Such signatures of WM include changes in firing rate or local oscillatory power within an area, along with measures of coordinated activity between areas based on synchronization between oscillations. In comparing the ability of various neural signatures in any brain area to predict behavioral performance, we observe that synchrony between areas is more frequently and robustly correlated with WM performance than any of the within-area neural signatures. We further review the evidence for alteration of inter-areal synchrony in brain disorders, consistent with an important role for such synchrony during behavior. Additionally, results of causal studies indicate that manipulating synchrony across areas is especially effective at influencing WM task performance. Each of these lines of research supports the critical role of inter-areal synchrony in WM. Finally, we propose a framework for interactions between prefrontal and sensory areas during WM, incorporating a range of experimental findings and offering an explanation for the observed link between intra-areal measures and WM performance.

AAV11 permits efficient retrograde targeting of projection neurons

Viral tracers that permit efficient retrograde targeting of projection neurons are powerful vehicles for structural and functional dissections of the neural circuit and for the treatment of brain diseases. Recombinant adeno-associated viruses (rAAVs) are the most potential candidates because they are low-toxic with high-level transgene expression and minimal host immune responses. Currently, some rAAVs based on capsid engineering for retrograde tracing have been widely used in the analysis and manipulation of neural circuits, but suffer from brain area selectivity and inefficient retrograde transduction in certain neural connections. Here, we discovered that the recombinant adeno-associated virus 11 (rAAV11) exhibits potent retrograde labeling of projection neurons with enhanced efficiency to rAAV2-retro in some neural connections. Combined with calcium recording technology, rAAV11 can be used to monitor neuronal activities by expressing Cre recombinase or calcium-sensitive functional probe. In addition, we further showed the suitability of rAAV11 for astrocyte targeting. These properties make rAAV11 a promising tool for the mapping and manipulation of neural circuits and gene therapy of some neurological and neurodegenerative disorders.

Spatiotemporal Patterns of Adaptation-Induced Slow Oscillations in a Whole-Brain Model of Slow-Wave Sleep

During slow-wave sleep, the brain is in a self-organized regime in which slow oscillations (SOs) between up- and down-states travel across the cortex. While an isolated piece of cortex can produce SOs, the brain-wide propagation of these oscillations are thought to be mediated by the long-range axonal connections. We address the mechanism of how SOs emerge and recruit large parts of the brain using a whole-brain model constructed from empirical connectivity data in which SOs are induced independently in each brain area by a local adaptation mechanism. Using an evolutionary optimization approach, good fits to human resting-state fMRI data and sleep EEG data are found at values of the adaptation strength close to a bifurcation where the model produces a balance between local and global SOs with realistic spatiotemporal statistics. Local oscillations are more frequent, last shorter, and have a lower amplitude. Global oscillations spread as waves of silence across the undirected brain graph, traveling from anterior to posterior regions. These traveling waves are caused by heterogeneities in the brain network in which the connection strengths between brain areas determine which areas transition to a down-state first, and thus initiate traveling waves across the cortex. Our results demonstrate the utility of whole-brain models for explaining the origin of large-scale cortical oscillations and how they are shaped by the connectome.

Spindle-Shaped Neurons in the Human Posteromedial (Precuneus) Cortex

The human posteromedial cortex (PMC), which includes the precuneus (PC), represents a multimodal brain area implicated in emotion, conscious awareness, spatial cognition, and social behavior. Here, we describe the presence of Nissl-stained elongated spindle-shaped neurons (suggestive of von Economo neurons, VENs) in the cortical layer V of the anterior and central PC of adult humans. The adapted “single-section” Golgi method for postmortem tissue was used to study these neurons close to pyramidal ones in layer V until merging with layer VI polymorphic cells. From three-dimensional (3D) reconstructed images, we describe the cell body, two main longitudinally oriented ascending and descending dendrites as well as the occurrence of spines from proximal to distal segments. The primary dendritic shafts give rise to thin collateral branches with a radial orientation, and pleomorphic spines were observed with a sparse to moderate density along the dendritic length. Other spindle-shaped cells were observed with straight dendritic shafts and rare branches or with an axon emerging from the soma. We discuss the morphology of these cells and those considered VENs in cortical areas forming integrated brain networks for higher-order activities. The presence of spindle-shaped neurons and the current discussion on the morphology of putative VENs address the need for an in-depth neurochemical and transcriptomic characterization of the PC cytoarchitecture. These findings would include these spindle-shaped cells in the synaptic and information processing by the default mode network and for general intelligence in healthy individuals and in neuropsychiatric disorders involving the PC in the context of the PMC functioning.

Children with Strabismus and Amblyopia Presented Abnormal Spontaneous Brain Activities Measured through Fractional Amplitude of Low-frequency Fluctuation (fALFF)

Purpose: Based on fMRI technology, we explored whether children with strabismus and amblyopia (SA) showed significant change in fractional amplitude of low-frequency fluctuation (fALFF) values in specific brain regions compared with healthy controls, and whether this change could point to the clinical manifestations and pathogenesis of children with strabismus to a certain extent.Methods: We enrolled 23 children with SA and same number matched healthy control in the ophthalmology department of the First Affiliated Hospital of Nanchang University, and the whole brain was scanned by rs-fMRI. The fALFF value of each brain area was derived to examine whether there is a statistical difference in the two groups. Meanwhile, ROC curve was made in a view to evaluate whether this difference proves useful as a diagnostic index. Finally, analyze whether changes in the fALFF value of some specific brain regions are related to clinical manifestations.Results: report to HCs children with SA presented a decreased fALFF values in left temporal pole: the superior temporal gyrus, right middle temporal gyrus, right superior frontal gyrus, right supplementary motor area. Meanwhile, they also showed higher fALFF values in specific brain areas, which included left precentral gyrus, left inferior Parietal, left Precuneus.Conclusion: Children with SA showed abnormal fALFF values in different brain regions. Most of these regions were allocated to the visual formation pathway. The eye movement-related pathway or other visual-related pathways, suggesting the pathological mechanism of the patient.

Relevance of a Novel Circuit-Level Model of Episodic Memories to Alzheimer’s Disease

The medial temporal lobe memory system has long been identified as the brain region showing the first histopathological changes in early Alzheimer’s disease (AD), and the functional decline observed in patients also points to a loss of function in this brain area. Nonetheless, the exact identity of the neurons and networks that undergo deterioration has not been determined so far. A recent study has identified the entorhinal and hippocampal neural circuits responsible for encoding new episodic memories. Using this novel model we describe the elements of the episodic memory network that are especially vulnerable in early AD. We provide a hypothesis of how reduced reelin signaling within such a network can promote AD-related changes. Establishing novel associations and creating a temporal structure for new episodic memories are both affected in AD. Here, we furnish a reasonable explanation for both of these previous observations.

Behavioral Prioritization Enhances Working Memory Precision and Neural Population Gain

Humans allocate visual working memory (WM) resource according to behavioral relevance, resulting in more precise memories for more important items. Theoretically, items may be maintained by feature-tuned neural populations, where the relative gain of the populations encoding each item determines precision. To test this hypothesis, we compared the amplitudes of delay period activity in the different parts of retinotopic maps representing each of several WM items, predicting the amplitudes would track behavioral priority. Using fMRI, we scanned participants while they remembered the location of multiple items over a WM delay and then reported the location of one probed item using a memory-guided saccade. Importantly, items were not equally probable to be probed (0.6, 0.3, 0.1, 0.0), which was indicated with a precue. We analyzed fMRI activity in 10 visual field maps in occipital, parietal, and frontal cortex known to be important for visual WM. In early visual cortex, but not association cortex, the amplitude of BOLD activation within voxels corresponding to the retinotopic location of visual WM items increased with the priority of the item. Interestingly, these results were contrasted with a common finding that higher-level brain regions had greater delay period activity, demonstrating a dissociation between the absolute amount of activity in a brain area and the activity of different spatially selective populations within it. These results suggest that the distribution of WM resources according to priority sculpts the relative gains of neural populations that encode items, offering a neural mechanism for how prioritization impacts memory precision.

Protective effects of Derinat, a nucleotide-based drug, on experimental traumatic brain injury, and its cellular mechanisms

Traumatic brain injury is the most common cause of death and disability in young people including sport athletes and soldiers, people under 45 years of age in the industrialized countries, representing a growing health problem in developing countries, as well as in aging communities. Treatment of the latter is a serious challenge for modern medicine. This type of injury leads to many kinds of disorders and, quite often, to disability. These issue require development of new methods for brain trauma treatment. The new approach to brain trauma treatment was studied in murine experiments. In particular, sodium salt of deoxyribonucleic acid (DNA) was used. This preparation is a drug known as a mixture of peptides with immunomodulatory effect which is widely used for different kinds of therapy. Derinat, a sodium salt of DNA, isolated from the caviar of Russian sturgeon, is a proven immunomodulator for treatment of diseases associatd with reactive oxygen species (ROS), including brain ischemia-reperfusion (IR) injury. Here we show that treatment with Derinat exert neuroprotective, anti-oxidative, and anti-inflammatory effects in experimental model of traumatic brain injury (TBI) in rats. Intraperitoneal injection of Derinat several times over 3 days after TBI showed less pronounced damage of the injured brain area. Immunohistochemical study showed that the Derinat-induced morphological changes of microglia in cerebral cortex and hippocampus 7 days after TBI. TBI-induced accumulation of 8-oxoguanine (8-oxoG), the marker of oxidative damage, was significantly attenuated by Derinat administration, both on 7th and 14th day after TBI. To investigate cellular mechanism of anti-inflammatory effects, the primary cultures of murine microglia supplied with ATP (50 M and 1 mM), as a substance released at injured site, were used to mimic the in vitro inflammatory response. Derinate treatment caused an increase of glial levels of mRNAs encoding neurotrophic factor (GDNF) and nerve growth factor (NGF) in the presence of ATP, whereas tissue plasminogen activator (tPA) mRNA was inhibited by ATP with or without Derinat. Interleukin-6 (IL-6) mRNA expression was not affected by ATP but was increased by Derinat. Both mRNA and protein levels of ATP-induced TNFα production were significantly inhibited by Derinat. These results partially contribute to understanding mechanisms of immunomodulatory effects of DNA preparations in traumatic brain injury.