Distinct Brain Areas Research Articles

PACAP regulates neuroendocrine and behavioral stress responses via CRF-containing neurons of the rat hypothalamic paraventricular nucleus

AbstractPituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide widely distributed in the brain including the hypothalamic paraventricular nucleus (PVN) implying a regulatory role in stress function. Recent evidence indicates that one of the main targets of PACAP within the PVN are corticotropin-releasing factor (CRF) neurons, which are key regulators of the hypothalamic-pituitary-adrenal (HPA) axis. However, the neural correlates that mediate PACAP effects on stress function are not fully understood. In the present study, we characterized the neuronal mechanism by which PACAP regulates neuroendocrine and behavioral stress responses in rats. We found that intracerebroventricular administration of PACAP increased the swim stress-induced c-Fos expression in distinct brain areas of the stress and anxiety circuitry including the parvocellular part of the PVN and changed behavioral stress coping during forced swimming to a more passive coping style (i.e., indicated by increased floating and reduced struggling behavior). Subsequently, PACAP administration directly into the PVN mimicked these behavioral effects and potentiated the plasma ACTH response to forced swim stress suggesting an excitatory role of PACAP on HPA stress axis reactivity. In addition, immunohistochemical analysis revealed a considerable portion of stress-activated CRF neurons in the medial parvocellular part of the PVN that co-localized PAC1 receptors suggesting that PACAP-induced effects on stress function are likely mediated directly by activation of CRF neurons in the PVN. Thus, these findings suggest that the PVN may represent one of the key areas where PACAP regulates the neuroendocrine and behavioral stress response.

The BDNF-ERK/MAPK axis reduces phosphatase and actin regulator1, 2 and 3 (PHACTR1, 2 and 3) mRNA expressions in cortical neurons.

Actin rearrangement and phosphorylation-dephosphorylation in the nervous system contribute to plastic alteration of neuronal structure and function. Phosphatase and actin regulator (PHACTR) family members are actin- and protein phosphatase 1 (PP1)-binding proteins. Because some family members act as regulators of neuronal morphology, studying the regulatory mechanisms of PHACTR is valuable for understanding the basis of neuronal circuit formation. Although expression patterns of PHACTR family molecules (PHACTR1-4) vary across distinct brain areas, little is known about the extracellular ligands that influence their mRNA levels. In this study, we focused on an important neurotrophin, brain-derived neurotrophic factor (BDNF), and examined its effect on mRNA expression of PHACTR family member in cortical neurons. PHACTR1-3, but not PHACTR4, were affected by stimulation of primary cultured cortical neurons with BDNF; namely, sustained downregulation of their mRNA levels was observed. The observed downregulation was blocked by an inhibitor of the extracellular signal-regulated protein kinase/mitogen-activated protein kinase (ERK/MAPK) pathway, U0126, suggesting that ERK/MAPK plays an inhibitory role for gene induction of PHACTR1-3. These findings aid the elucidation of how BDNF regulates actin- and PP1-related neuronal functions.

Whole-Brain Vascular Architecture Mapping Identifies Region-Specific Microvascular Profiles In Vivo.

The novel MR imaging technique of vascular architecture mapping allows in vivo characterization of local changes in cerebral microvasculature, but reference ranges for vascular architecture mapping parameters in healthy brain tissue are lacking, limiting its potential applicability as an MR imaging biomarker in clinical practice. We conducted whole-brain vascular architecture mapping in a large cohort to establish vascular architecture mapping parameter references ranges and identify region-specific cortical and subcortical microvascular profiles. This was a single-center examination of adult patients with unifocal, stable low-grade gliomas with multiband spin- and gradient-echo EPI sequence at 3T using parallel imaging. Voxelwise plotting of resulting values for gradient-echo (R2*) versus spin-echo (R2) relaxation rates during contrast agent bolus administration generates vessel vortex curves that allow the extraction of vascular architecture mapping parameters representative of, eg, vessel type, vessel radius, or CBV in the underlying voxel. Averaged whole-brain parametric maps were calculated for 9 parameters, and VOI analysis was conducted on the basis of a standardized brain atlas and individual cortical GM and WM segmentation. Prevalence of vascular risk factors among subjects (n = 106; mean age, 39.2 [SD, 12.5] years; 56 women) was similar to those in the German population. Compared with WM, we found cortical GM to have larger mean vascular calibers (5.80 [SD, 0.59] versus 4.25 [SD, 0.62] P < .001), increased blood volume fraction (20.40 [SD, 4.49] s-1 versus 11.05 [SD, 2.44] s-1; P < .001), and a dominance of venous vessels. Distinct microvascular profiles emerged for cortical GM, where vascular architecture mapping vessel type indicator differed, eg, between the thalamus and cortical GM (mean, -2.47 [SD, 4.02] s-2 versus -5.41 [SD, 2.84] s-2; P < .001). Intraclass correlation coefficient values indicated overall high test-retest reliability for vascular architecture mapping parameter mean values when comparing multiple scans per subject. Whole-brain vascular architecture mapping in the adult brain reveals region-specific microvascular profiles. The obtained parameter reference ranges for distinct anatomic and functional brain areas may be used for future vascular architecture mapping studies on cerebrovascular pathologies and might facilitate early discovery of microvascular changes, in, eg, neurodegeneration and neuro-oncology.

Same Same, But Different: Brain Areas Underlying the Learning from Repetitive Episodic Prediction Errors.

Prediction errors (PEs) function as learning signals. It is yet unclear how varying compared to repetitive PEs affect episodic memory in brain and behavior. The current study investigated cerebral and behavioral effects of experiencing either multiple alternative versions ("varying") or one single alternative version ("repetitive") of a previously encoded episode. Participants encoded a set of episodes ("originals") by watching videos showing toy stories. During scanning, participants either experienced originals, one single, or multiple alternative versions of the previously encoded episodes. Participants' memory performance was tested through recall of original objects. Varying and repetitive PEs revealed typical brain responses to the detection of mismatching information including inferior frontal and posterior parietal regions, as well as hippocampus, which is further linked to memory reactivation, and the amygdala, known for modulating memory consolidation. Furthermore, experiencing varying and repetitive PEs triggered distinct brain areas as revealed by direct contrast. Among others, experiencing varying versions triggered activity in the caudate, a region that has been associated with PEs. In contrast, repetitive PEs activated brain areas that resembled more those for retrieval of originally encoded episodes. Thus, ACC and posterior cingulate cortex activation seemed to serve both reactivating old and integrating new but similar information in episodic memory. Consistent with neural findings, participants recalled original objects less accurately when only presented with the same, but not varying, PE during fMRI. The current findings suggest that repeated PEs interact more strongly with a recalled original episodic memory than varying PEs.

Attenuation of Nerve Agent Induced Neurodegenerative and Neuroinflammatory Changes in Rats with New Combination Treatment of Galantamine, Atropine and Midazolam.

Acute nerve agent exposure can kill a person within minutes or produce multiple neurotoxic effects and subsequent brain damage with potential long-term adverse outcomes. Recent abuse of nerve-agents on Syrian civilians, during Japan terrorist attacks, and personal assassinations in the UK, and Malaysia indicate their potential threat to world population. Existing nerve agent antidotes offer only incomplete protection especially, if the treatment is delayed. To develop the effective drugs, it is advantageous to elucidate the underlying mechanisms of nerve agent-induced multiple neurological impairments. This study aimed to investigate the molecular basis of neuroinflammation during nerve agent toxicity with focus on inflammasome-associated proteins and neurodegeneration. In rats, NOD-like receptor family pyrin domain containing 3 (NLRP3), and glial fibrillary acidic protein (GFAP) immunoreactivity levels were considerably increased in the hippocampus, piriform cortex, and amygdala areas after single subcutaneous soman exposure (90µg/kg-1). Western analysis indicated a notable increase in the neuroinflammatory indicator proteins, high mobility group box 1 (HMGB1) and inducible nitric oxide synthase (iNOS) levels. The presence of fluorojade-C-stained degenerating neurons in distinct rat brain areas is indicating the neurodegeneration during nerve agent toxicity. Pre-treatment with galantamine (3mg/kg, - 30min) followed by post-treatment of atropine (10mg/kg, i.m.) and midazolam (5mg/kg, i.m.), has completely protected animals from death induced by supra-lethal dose of soman (2XLD50) and reduced the neuroinflammatory and neurodegenerative changes. Results highlight that this new prophylactic and therapeutic drug combination might be an effective treatment option for soldiers deployed in conflict areas and first responders dealing with accidental/deliberate release of nerve agents.

The tip of the iceberg: A call to embrace anti-localizationism in human neuroscience research

Abstract Human neuroscience research remains largely preoccupied with mapping distinct brain areas to complex psychological processes and features of mental health disorders. While this reductionist and localizationist perspective has resulted in several substantive contributions to the field, it has long been viewed as only a piece of the puzzle. Emerging evidence now empirically demonstrates how a historical reliance on localizationist techniques may underlie recent challenges to reproducibility and translation in human neuroscience. To advance discovery, we must collectively better incorporate complex systems and machine-learning approaches that better capture the multidimensional, dynamic, and interacting nature of the brain. Moreover, we must begin to contend with how to best integrate complementary modalities beyond the brain to better understand complex mental processes.

Neural correlates of recalled sadness, joy, and fear states: a source reconstruction EEG study.

The capacity to understand the others' emotional states, particularly if negative (e.g. sadness or fear), underpins the empathic and social brain. Patients who cannot express their emotional states experience social isolation and loneliness, exacerbating distress. We investigated the feasibility of detecting non-invasive scalp-recorded electrophysiological signals that correspond to recalled emotional states of sadness, fear, and joy for potential classification. The neural activation patterns of 20 healthy and right-handed participants were studied using an electrophysiological technique. Analyses were focused on the N400 component of Event-related potentials (ERPs) recorded during silent recall of subjective emotional states; Standardized weighted Low-resolution Electro-magnetic Tomography (swLORETA) was employed for source reconstruction. The study classified individual patterns of brain activation linked to the recollection of three distinct emotional states into seven regions of interest (ROIs). Statistical analysis (ANOVA) of the individual magnitude values revealed the existence of a common emotional circuit, as well as distinct brain areas that were specifically active during recalled sad, happy and fearful states. In particular, the right temporal and left superior frontal areas were more active for sadness, the left limbic region for fear, and the right orbitofrontal cortex for happy affective states. In conclusion, this study successfully demonstrated the feasibility of detecting scalp-recorded electrophysiological signals corresponding to internal and subjective affective states. These findings contribute to our understanding of the emotional brain, and have potential applications for future BCI classification and identification of emotional states in LIS patients who may be unable to express their emotions, thus helping to alleviate social isolation and sense of loneliness.

Exploring Physiological Differences in Brain Areas Using Statistical Complexity Analysis of BOLD Signals.

The brain is a fundamental organ for the human body to function properly, for which it needs to receive a continuous flow of blood, which explains the existence of control mechanisms that act to maintain this flow as constant as possible in a process known as cerebral autoregulation. One way to obtain information on how the levels of oxygen supplied to the brain vary is through of BOLD (Magnetic Resonance) images, which have the advantage of greater spatial resolution than other forms of measurement, such as transcranial Doppler. However, they do not provide good temporal resolution nor allow for continuous prolonged examination. Thus, it is of great importance to find a method to detect regional differences from short BOLD signals. One of the existing alternatives is complexity measures that can detect changes in the variability and temporal organisation of a signal that could reflect different physiological states. The so-called statistical complexity, created to overcome the shortcomings of entropy alone to explain the concept of complexity, has shown potential with haemodynamic signals. The aim of this study is to determine by using statistical complexity whether it is possible to find differences between physiologically distinct brain areas in healthy individuals. The data set includes BOLD images of 10 people obtained at the University Hospital of Leicester NHS Trust with a 1.5 Tesla magnetic resonance imaging scanner. The data were captured for 180 s at a frequency of 1 Hz. Using various combinations of statistical complexities, no differences were found between hemispheres. However, differences were detected between grey matter and white matter, indicating that these measurements are sensitive to differences in brain tissues.

Age-related changes in the architecture and biochemical markers levels in motor-related cortical areas of SHR rats-an ADHD animal model.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder whose exact pathophysiology has not been fully understood yet. Numerous studies have suggested disruptions in the cellular architecture and neuronal activity within brain structures of individuals with ADHD, accompanied by imbalances in the immune system, oxidative stress, and metabolism. This study aims to assess two functionally and histologically distinct brain areas involved in motor control and coordination: the motor cortex (MC) and prefrontal cortex (PFC). Namely, the morphometric analysis of the MC throughout the developmental stages of Spontaneously Hypertensive Rats (SHRs) and Wistar Kyoto Rats (WKYs). Additionally, the study aimed to investigate the levels and activities of specific immune, oxidative stress, and metabolic markers in the PFC of juvenile and maturing SHRs in comparison to WKYs. The most significant MC volume reductions occurred in juvenile SHRs, accompanied by alterations in neuronal density in these brain areas compared to WKYs. Furthermore, juvenile SHRs exhibit heightened levels and activity of various markers, including interleukin-1α (IL-1α), IL-6, serine/threonine-protein mammalian target of rapamycin, RAC-alpha serine/threonine-protein kinase, glucocorticoid receptor β, malondialdehyde, sulfhydryl groups, superoxide dismutase, peroxidase, glutathione reductase, glutathione S-transferase, glucose, fructosamine, iron, lactic acid, alanine, aspartate transaminase, and lactate dehydrogenase. Significant changes in the MC morphometry and elevated levels of inflammatory, oxidative, and metabolic markers in PFC might be associated with disrupted brain development and maturation in ADHD.

A preclinical model of TB meningitis to determine drug penetration and activity at the sites of disease.

Tuberculosis meningitis (TBM) is essentially treated with the first-line regimen used against pulmonary tuberculosis, with a prolonged continuation phase. However, clinical outcomes are poor in comparison, for reasons that are only partially understood, highlighting the need for improved preclinical tools to measure drug distribution and activity at the site of disease. A predictive animal model of TBM would also be of great value to prioritize promising drug regimens to be tested in clinical trials, given the healthy state of the development pipeline for the first time in decades. Here, we report the optimization of a rabbit model of TBM disease induced via inoculation of Mycobacterium tuberculosis into the cisterna magna, recapitulating features typical of clinical TBM: neurological deterioration within months post-infection, acid-fast bacilli in necrotic lesions in the brain and spinal cord, and elevated lactate levels in cerebrospinal fluid (CSF). None of the infected rabbits recovered or controlled the disease. We used young adult rabbits, the size of which allows for spatial drug quantitation in critical compartments of the central nervous system that cannot be collected in clinical studies. To illustrate the translational value of the model, we report the penetration of linezolid from plasma into the CSF, meninges, anatomically distinct brain areas, cervical spine, and lumbar spine. Across animals, we measured the bacterial burden concomitant with neurological deterioration, offering a useful readout for drug efficacy studies. The model thus forms the basis for building a preclinical platform to identify improved regimens and inform clinical trial design.

Reward is not reward: Differential impacts of primary and secondary rewards on expectation, outcome, and prediction error in the human brain's reward processing regions

According to their nature, rewarding stimuli are classified as primary (e.g., food, sex) and secondary (e.g., money) rewards. Neuroimaging studies have provided valuable insights in neural reward processing and its various aspects including reward expectation, outcome and prediction error encoding. However, there is only limited evidence of whether the two different types of rewards are processed in common or distinct brain areas, in particular when considering the different functions of reward processing. We analyzed a sample of 42 healthy, male participants using task-based functional magnetic resonance imaging (fMRI) during a variant of the monetary incentive delay task. We aimed to investigate the effects of three different rewarding stimuli—two primary (food and sex) and one secondary (money)—on the various functions of reward processing. To provide a thorough description, we focused on 12 brain regions of interest and utilized the Bayes factor bound (BFB) to express stimulus-related main effects and pairwise differences at different levels of evidence, ranging from weak to decisive. Our results revealed a dominance of sexually charged stimuli in engaging the brain's reward structures for all investigated aspects of reward processing. Nevertheless, the ventral tegmental area, amygdala, ventral caudate, ventromedial prefrontal cortex, subgenual anterior cingulate cortex, and lateral orbitofrontal cortex were activated by both primary and secondary reward outcomes. For other reward processing functions, i.e., reward expectation and the prediction error, effects of the different stimuli were weaker, and effects from one reward type cannot easily be generalized to the other.

Intermediately synchronised brain states optimise trade-off between subject specificity and predictive capacity

Functional connectivity (FC) refers to the statistical dependencies between activity of distinct brain areas. To study temporal fluctuations in FC within the duration of a functional magnetic resonance imaging (fMRI) scanning session, researchers have proposed the computation of an edge time series (ETS) and their derivatives. Evidence suggests that FC is driven by a few time points of high-amplitude co-fluctuation (HACF) in the ETS, which may also contribute disproportionately to interindividual differences. However, it remains unclear to what degree different time points actually contribute to brain-behaviour associations. Here, we systematically evaluate this question by assessing the predictive utility of FC estimates at different levels of co-fluctuation using machine learning (ML) approaches. We demonstrate that time points of lower and intermediate co-fluctuation levels provide overall highest subject specificity as well as highest predictive capacity of individual-level phenotypes.

Effect of Visual Feedback on Behavioral Control and Functional Activity During Bilateral Hand Movement.

Previous researches state vision as a vital source of information for movement control and more precisely for accurate hand movement. Further, fine bimanual motor activity may be associated with various oscillatory activities within distinct brain areas and inter-hemispheric interactions. However, neural coordination among the distinct brain areas responsible to enhance motor accuracy is still not adequate. In the current study, we investigated task-dependent modulation by simultaneously measuring high time resolution electroencephalogram (EEG), electromyogram (EMG) and force along with bi-manual and unimanual motor tasks. The errors were controlled using visual feedback. To complete the unimanual tasks, the participant was asked to grip the strain gauge using the index finger and thumb of the right hand thereby exerting force on the connected visual feedback system. Whereas the bi-manual task involved finger abduction of the left index finger in two contractions along with visual feedback system and at the same time the right hand gripped using definite force on two conditions that whether visual feedback existed or not for the right hand. Primarily, the existence of visual feedback for the right hand significantly decreased brain network global and local efficiency in theta and alpha bands when compared with the elimination of visual feedback using twenty participants. Brain network activity in theta and alpha bands coordinates to facilitate fine hand movement. The findings may provide new neurological insight on virtual reality auxiliary equipment and participants with neurological disorders that cause movement errors requiring accurate motor training. The current study investigates task-dependent modulation by simultaneously measuring high time resolution electroencephalogram, electromyogram and force along with bi-manual and unimanual motor tasks. The findings show that visual feedback for right hand decreases the force root mean square error of right hand. Visual feedback for right hand decreases local and global efficiency of brain network in theta and alpha bands.

Brain mapping: topography of neurons and their transmitters involved in various brain functions.

Use of the demanding techniques microdialysis or push-pull superfusion makes it possible to identify neurons in distinct brain areas involved in central control of peripheral functions, thus enabling brain mapping. Investigations with the push-pull superfusion technique have shown that mainly catecholaminergic neurons of the posterior and anterior hypothalamus, the locus coeruleus, and the nucleus of the solitary tract are of crucial importance for blood pressure regulation. Experimentally induced blood pressure changes also modify the release of histamine, glutamate, and taurine in the posterior hypothalamus and of serotonin in the locus coeruleus. Furthermore, histaminergic neurons of the nucleus accumbens are involved in memory, serotonergic neurons of the locus coeruleus in response to noxious stimuli, while nitric oxide of striatum has been implicated in neurotoxicity elicited by amphetamines. The involvement of several neurons in one brain function is discussed.

RETRACTED ARTICLE: Functional modular networks identify the pivotal genes associated with morphine addiction and potential drug therapies

Background Chronic morphine usage induces lasting molecular and microcellular adaptations in distinct brain areas, resulting in addiction-related behavioural abnormalities, drug-seeking, and relapse. Nonetheless, the mechanisms of action of the genes responsible for morphine addiction have not been exhaustively studied.MethodsWe obtained morphine addiction-related datasets from the Gene Expression Omnibus (GEO) database and screened for Differentially Expressed Genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) functional modularity constructs were analyzed for genes associated with clinical traits. Venn diagrams were filtered for intersecting common DEGs (CDEGs). Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for functional annotation. Protein–protein interaction network (PPI) and CytoHubba were used to screen for hub genes. Potential treatments for morphine addiction were figured out with the help of an online database.ResultsSixty-five common differential genes linked to morphine addiction were identified, and functional enrichment analysis showed that they were primarily involved in ion channel activity, protein transport, the oxytocin signalling pathway, neuroactive ligand-receptor interactions, and other signalling pathways. Based on the PPI network, ten hub genes (CHN2, OLIG2, UGT8A, CACNB2, TIMP3, FKBP5, ZBTB16, TSC22D3, ISL1, and SLC2A1) were checked. In the data set GSE7762, all of the Area Under Curve (AUC) values for the hub gene Receiver Operating Characteristic (ROC) curves were greater than 0.8. We also used the DGIdb database to look for eight small-molecule drugs that might be useful for treating morphine addiction.ConclusionsThe hub genes are crucial genes associated with morphine addiction in the mouse striatum. The oxytocin signalling pathway may play a vital role in developing morphine addiction.

Neuronal properties of pyramidal cells in lateral prefrontal cortex of the aging rhesus monkey brain are associated with performance deficits on spatial working memory but not executive function.

Age-related declines in cognitive abilities occur as early as middle-age in humans and rhesus monkeys. Specifically, performance by aged individuals on tasks of executive function (EF) and working memory (WM) is characterized by greater frequency of errors, shorter memory spans, increased frequency of perseverative responses, impaired use of feedback and reduced speed of processing. However, how aging precisely differentially impacts specific aspects of these cognitive functions and the distinct brain areas mediating cognition are not well understood. The prefrontal cortex (PFC) is known to mediate EF and WM and is an area that shows a vulnerability to age-related alterations in neuronal morphology. In the current study, we show that performance on EF and WM tasks exhibited significant changes with age, and these impairments correlate with changes in biophysical properties of layer 3 (L3) pyramidal neurons in lateral LPFC (LPFC). Specifically, there was a significant age-related increase in excitability of L3 LPFC pyramidal neurons, consistent with previous studies. Further, this age-related hyperexcitability of LPFC neurons was significantly correlated with age-related decline on a task of WM, but not an EF task. The current study characterizes age-related performance on tasks of WM and EF and provides insight into the neural substrates that may underlie changes in both WM and EF with age.

Investigating Intra-Individual Networks of Response Inhibition and Interference Resolution using 7T MRI

Response inhibition and interference resolution are often considered subcomponents of an overarching inhibition system that utilizes the so-called cortico-basal-ganglia loop. Up until now, most previous functional magnetic resonance imaging (fMRI) literature has compared the two using between-subject designs, pooling data in the form of a meta-analysis or comparing different groups. Here, we investigate the overlap of activation patterns underlying response inhibition and interference resolution on a within-subject level, using ultra-high field MRI. In this model-based study, we furthered the functional analysis with cognitive modelling techniques to provide a more in-depth understanding of behaviour. We applied the stop-signal task and multi-source interference task to measure response inhibition and interference resolution, respectively. Our results lead us to conclude that these constructs are rooted in anatomically distinct brain areas and provide little evidence for spatial overlap. Across the two tasks, common BOLD responses were observed in the inferior frontal gyrus and anterior insula. Interference resolution relied more heavily on subcortical components, specifically nodes of the commonly referred to indirect and hyperdirect pathways, as well as the anterior cingulate cortex, and pre-supplementary motor area. Our data indicated that orbitofrontal cortex activation is specific to response inhibition. Our model-based approach provided evidence for the dissimilarity in behavioural dynamics between the two tasks. The current work exemplifies the importance of reducing inter-individual variance when comparing network patterns and the value of UHF-MRI for high resolution functional mapping.

Exploration of static functional connectivity and dynamic functional connectivity alterations in the primary visual cortex among patients with high myopia via seed-based functional connectivity analysis.

This study was conducted to explore differences in static functional connectivity (sFC) and dynamic functional connectivity (dFC) alteration patterns in the primary visual area (V1) among high myopia (HM) patients and healthy controls (HCs) via seed-based functional connectivity (FC) analysis. Resting-state functional magnetic resonance imaging (fMRI) scans were performed on 82 HM patients and 59 HCs who were closely matched for age, sex, and weight. Seed-based FC analysis was performed to identify alterations in the sFC and dFC patterns of the V1 in HM patients and HCs. Associations between mean sFC and dFC signal values and clinical symptoms in distinct brain areas among HM patients were identified via correlation analysis. Static and dynamic changes in brain activity in HM patients were investigated by assessments of sFC and dFC via calculation of the total time series mean and sliding-window analysis. In the left anterior cingulate gyrus (L-ACG)/left superior parietal gyrus (L-SPG) and left V1, sFC values were significantly greater in HM patients than in HCs. In the L-ACG and right V1, sFC values were also significantly greater in HM patients than in HCs [two-tailed, voxel-level P < 0.01, Gaussian random field (GRF) correction, cluster-level P < 0.05]. In the left calcarine cortex (L-CAL) and left V1, dFC values were significantly lower in HM patients than in HCs. In the right lingual gyrus (R-LING) and right V1, dFC values were also significantly lower in HM patients than in HCs (two-tailed, voxel-level P < 0.01, GRF correction, cluster-level P < 0.05). Patients with HM exhibited significantly disturbed FC between the V1 and various brain regions, including L-ACG, L-SPG, L-CAL, and R-LING. This disturbance suggests that patients with HM could exhibit impaired cognitive and emotional processing functions, top-down control of visual attention, and visual information processing functions. HM patients and HCs could be distinguished from each other with high accuracy using sFC and dFC variabilities. These findings may help to identify the neural mechanism of decreased visual performance in HM patients.

Depression-Associated Negr1 Gene-Deficiency Induces Alterations in the Monoaminergic Neurotransmission Enhancing Time-Dependent Sensitization to Amphetamine in Male Mice.

In GWAS studies, the neural adhesion molecule encoding the neuronal growth regulator 1 (NEGR1) gene has been consistently linked with both depression and obesity. Although the linkage between NEGR1 and depression is the strongest, evidence also suggests the involvement of NEGR1 in a wide spectrum of psychiatric conditions. Here we show the expression of NEGR1 both in tyrosine- and tryptophan hydroxylase-positive cells. Negr1-/- mice show a time-dependent increase in behavioral sensitization to amphetamine associated with increased dopamine release in both the dorsal and ventral striatum. Upregulation of transcripts encoding dopamine and serotonin transporters and higher levels of several monoamines and their metabolites was evident in distinct brain areas of Negr1-/- mice. Chronic (23 days) escitalopram-induced reduction of serotonin and dopamine turnover is enhanced in Negr1-/- mice, and escitalopram rescued reduced weight of hippocampi in Negr1-/- mice. The current study is the first to show alterations in the brain monoaminergic systems in Negr1-deficient mice, suggesting that monoaminergic neural circuits contribute to both depressive and obesity-related phenotypes linked to the human NEGR1 gene.

Children's syntax is supported by the maturation of BA44 at 4years, but of the posterior STS at 3years of age.

Within the first years of life, children learn major aspects of their native language. However, the ability to process complex sentence structures, a core faculty in human language called syntax, emerges only slowly. A milestone in syntax acquisition is reached around the age of 4years, when children learn a variety of syntactic concepts. Here, we ask which maturational changes in the child's brain underlie the emergence of syntactically complex sentence processing around this critical age. We relate markers of cortical brain maturation to 3- and 4-year-olds' sentence processing in contrast to other language abilities. Our results show that distinct cortical brain areas support sentence processing in the two age groups. Sentence production abilities at 3years were associated with increased surface area in the most posterior part of the left superior temporal sulcus, whereas 4-year-olds showed an association with cortical thickness in the left posterior part of Broca's area, i.e. BA44. The present findings suggest that sentence processing abilities rely on the maturation of distinct cortical regions in 3- compared to 4-year-olds. The observed shift to more mature regions involved in processing syntactically complex sentences may underlie behavioral milestones in syntax acquisition at around 4years.