Critical Brain Research Articles

Systemic and Intra-Habenular Activation of the Orphan G Protein-Coupled Receptor GPR139 Decreases Compulsive-Like Alcohol Drinking and Hyperalgesia in Alcohol-Dependent Rats.

GPR139 is an orphan G protein-coupled receptor (GPCR) that is expressed mainly in the brain, with the highest expression in the medial habenula. The modulation of GPR139 receptor function has been hypothesized to be beneficial in the treatment of some mental disorders, but behavioral studies have not yet provided causal evidence of the role of GPR139 in brain dysfunction. Because of the high expression of GPR139 in the habenula, a critical brain region in addiction, we hypothesized that GPR139 may play role in alcohol dependence. Thus, we tested the effect of GPR139 receptor activation using the selective, brain-penetrant receptor agonist JNJ-63533054 on addiction-like behaviors in alcohol-dependent male rats. Systemic administration of JNJ-63533054 (30 mg/kg but not 10 mg/kg, p.o.) reversed the escalation of alcohol self-administration in alcohol-dependent rats, without affecting water or saccharin intake in dependent rats or alcohol intake in nondependent rats. Moreover, systemic JNJ-63533054 administration decreased withdrawal-induced hyperalgesia, without affecting somatic signs of alcohol withdrawal. Further analysis demonstrated that JNJ-63533054 was effective only in a subgroup of dependent rats that exhibited compulsive-like alcohol drinking. Finally, site-specific microinjection of JNJ-63533054 in the habenula but not interpeduncular nucleus (IPN) reduced both alcohol self-administration and withdrawal-induced hyperalgesia in dependent rats. These results provide robust preclinical evidence that GPR139 receptor activation reverses key addiction-like behaviors in dependent animals, suggest that GPR139 may be a novel target for the treatment of alcohol use disorder, and demonstrate that GPR139 is functionally relevant in regulating mammalian behavior.

S119. Low threshold Linked Quadri-Polar (LQP)-TceMEP during left middle cerebral artery aneurysm clipping: A case report

Introduction Traditional TceMEP stimultion (one anode and one cathode) during aneurysm surgery is limited due to the use of higher stimulation intensity ( ∼ 150 V) activating the motor tract at a subcortical level, bypassing the cortical and superficial subcortical level. (LQP)-TceMEP technique has the advantage of using two anodes and two cathodes stimulating electrodes bilaterally. Using lower threshold stimulation allows widening the range of current spread, and may activate a more cortical or superficial subcortical level. Methods A 65 year old female underwent an elective surgery for a left MCA bifurcation clipping. No history of neurological disease or contraindication for intraoperative neurophysiological monitoring (IONM). Image : 7 mm AP by 5 mm transverse by 6.5 mm cranio-caudal posteriorly projecting saccular aneurysm at the left middle cerebral artery (MCA) bifurcation. Baselines were obtained prior to incision, and Desfluorane:3.0%, Propofol:75 g/kg/min. Remifentanil 0.3 g/kg/min, was implemented for this case. We strongly recommend TIVA for this type of cases. SSEPs (MN-UN-PTN). (LQP)-TceMEP at low threshold (40–48 V), train of 4, ISI 1.5, PW:75. CMAP were recorded from distal muscles: brachioradialis or flexor carpi radialis, abductor pollicis brevis, first dorsal interosseous and abductor hallucis. EEG. Results After placement of the first temporary clip at the M1 position there were no (LQP)-TceMEP changes noted at 48 V/150 mA. After another temporary clip was placed at the aneurysm neck, the potentials remain stable at 48 V/152 mA. After placement of a longer clip at the base of the neck of the aneurysm, the (LQP)-TceMEP showed significant changes at 48 V/150 mA and the intensity was increased to 54 V/158 mA with no improvement noted; the surgical team was notified. The upper and lower extremities cortical component of the SSEPs remain unchanged related to aneurysm clipping.After approximately 20 min the (LQP)-TceMEP was able to be evoked, however at a higher stimulation intensity (60 V), which we hypothesized to be bypassing the area of injury. Conclusion The use of the (LQP)-TceMEP technique gave us the opportunity to monitor the motor pathway continuously without patient movement related to transcranial stimualtion and without interfering with the surgical procedure due to the low stimulation used in this case, (40–48 V). With low threshold stimulation, we assume activation of the motor tract at a cortical or superficial subcortical level without bypassing critical brain areas. (TIVA) strongly recommend (not in this case), we had reliable responses throughout the case (until the aforementioned incident), which was also dependent on the patient’s preexisting conditions and body type. After surgery, the patient demonstrated a pure motor deficit (right hemiplegia), expressive aphasia (Broca’s area) and normal sensation. Imaging studies showed cortical (left inferior frontal lobe) and subcortical stroke. Three months after surgery the patient recovered movement and speech.

Neuro-computational account of how mood fluctuations arise and affect decision making

The influence of mood on choices is a well-established but poorly understood phenomenon. Here, we suggest a three-fold neuro-computational account: (1) the integration of positive and negative events over time induce mood fluctuations, (2) which are underpinned by variations in the baseline activities of critical brain valuation regions, (3) which in turn modulate the relative weights assigned to key dimensions of choice options. We validate this model in healthy participants, using feedback in a quiz task to induce mood fluctuations, and a choice task (accepting vs. declining a motor challenge) to reveal their effects. Using fMRI, we demonstrate the pivotal role of the ventromedial prefrontal cortex and anterior insula, in which baseline activities respectively increase and decrease with theoretical mood level and respectively enhance the weighting of potential gains and losses during decision making. The same mechanisms might explain how decisions are biased in mood disorders at longer timescales.

Functional MRI technologies in the study of medication treatment effect on Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of late‐life dementia. Characterized by progressive neurodegeneration, the disease is expressed as gradual memory loss together with decline in cognitive abilities and other brain functions. Despite extensive research over the past decade, the cause and cure of AD both remain largely unknown. Several AD‐associated deficits have been targeted for interventions, including those based on amyloid‐beta, tau, and inflammation hypotheses. Only 2 types of medications—cholinesterase inhibitors and memantine—have been approved, to control the cognitive symptoms of AD such as the loss of memory, language, and executive function. Noninvasive in vivo functional magnetic resonance imaging (MRI) technologies, including the blood oxygen level‐dependent functional MRI, arterial spin labeling‐based perfusion MRI, and the proton magnetic resonance spectroscopy have been used to study the effect of ChEIs and memantine in the brain. Most of these studies have demonstrated increased functional activation and connectivity, increased regional brain blood flow and volume post‐treatment, and positive responses of critical brain metabolites reflecting neuronal status and functionality in patients with AD and mild cognitive impairment. The findings have contributed to the understanding of the mechanisms underlying the medication treatments and support the crucial role of functional MRI technologies in the development and refinement of AD medication therapies.

Exposure to opiates in male adolescent rats alters pain perception in the male offspring.

During the past decades, the use/misuse of opioids has increased dramatically among adolescent population. It is now well acknowledged that various morphological and physiological changes occur in the brain during adolescence. During this critical period, brain development and maturation could be affected by several factors including stress, drug abuse, nutritional status, etc. Although studies on transgenerational effects of substances such as alcohol, nicotine, and cocaine have focused on both paternal and maternal drug exposure, most reports on transgenerational effects of morphine are restricted to maternal exposure. Thus, in this study, we aimed to investigate the transgenerational effect of paternal morphine exposure during adolescence on pain perception and antinociceptive effect of morphine in rat offspring. Male rats received escalating doses of morphine for 10 days during postnatal days 31-40. Twenty days after the last morphine injection, male rats were mated with intact female rats, and then behavioral tests were conducted on the male offspring on postnatal day 60. Pain perception and morphine antinociception were evaluated using the formalin test. Our results demonstrated that morphine-sired and saline-sired animals differed in the interphase and phase 2 of the formalin test. These findings indicate a significant transgenerational effect of paternal morphine exposure on pain-related behaviors in rat offspring.

F15. DIFFERENTIAL EXPRESSION PATTERNS OF EPIDERMAL GROWTH FACTOR (EGF) AND IMMUNE SYSTEM MARKERS IN DORSOLATERAL PREFRONTAL (BA46) AND ORBITOFRONTAL (BA11) CORTICES IN SCHIZOPHRENIA AND MOOD DISORDER

BackgroundEnvironmental risk factors that operate at maternal, foetal and post-natal levels, causing immune activation are known risk factors for schizophrenia. How this risk is transduced is unknown but one plausible disease mechanism may be through immune activation perturbing central nervous system growth factor systems, such as the epidermal growth factor (EGF) system critical to neuronal differentiation, maturation and plasticity, altering neurodevelopment. These interactions between EGF and immune systems may involve specific critical brain regions and not others.MethodsThe expression of candidate genes from EGF and immune systems and related signalling pathways, including ligands, receptors and intermediary molecules, were examined in post-mortem dorsolateral prefrontal (DLPFC) (n=114 genes) and orbitofrontal cortical (OFC) (n=105 genes) tissues, from schizophrenia and mood disorder patients and healthy controls (n=68), using the Fluidigm Biomark qRT-PCR platform. Data were analysed by ANOVA or corresponding non-parametric test (Kruskal-Wallis) in GraphPad Prism 6/7 statistical software and p values were adjusted for multiple testing (Benjamini-Hochberg).ResultsIn DLPFC, 68 genes were significantly differently expressed between diagnostic groups. In comparison to healthy controls, 60 genes were differentially expressed in schizophrenia and 14 in the mood disorder group. Collectively these differentially expressed genes belonged predominantly to ERBB signalling and associated MAPK, PI3K and MTOR pathways and with immune pathways involving toll like receptor (TLR), TNF, nuclear factor kappa B (NFB), JAK-STAT, and complement signalling. Although there was some overlap the expression profiles in schizophrenia and mood disorder differed considerably. There were genes (n=15) with significantly lowered expression in both patient groups compared to controls which belonged predominantly to immune pathways such as TNF and TLR. However, 36 genes were differentially expressed between schizophrenia and mood disorder, all of them having lower expression in schizophrenia, predominantly representing pathways PI3K/MTOR, MAPK, TLR and TNF signalling via NFKB. Gene expression in EGF system signalling via MAPK and PI3K pathways, and interleukin signalling via JAK-STAT were significantly lower in schizophrenia than in mood disorder and healthy controls. ErbB4 was the only gene significantly elevated in a patient group (mood disorder) compared to the controls.In comparison to DLPFC, only five genes out of the 105 examined were differentially expressed between the diagnostic groups in OFC, which belonged to NFB, TLR, JAK-STAT and growth factor signalling pathways. In comparison to healthy controls all were differentially expressed in schizophrenia and three genes in the mood disorder group. The expression of most genes was decreased in the patient groups compared to control subjects in both brain regions.DiscussionWe conclude that there is a prominent regional difference in the expression of EGF and immune system markers, identifying the DLPFC as a region of high activity for the interaction between these two systems relative to the OFC. In this region, the differing profiles of gene expression between schizophrenia and mood disorder involved EGF signalling pathways including PI3K/MTOR and MAPK along with immune pathways such as TNF, TLR and JAK-STAT signalling, possibly reflecting variant pathological processes involving immune and EGF system signalling between these sets of disorders.

T99. LONG-TERM CANNABIS USE ASSOCIATED WITH ALTERED FUNCTIONING DURING VERBAL LEARNING

BackgroundLong-term use of cannabis has long been associated with changes in cognition, including memory and learning, particularly verbal learning in man. However, evidence regarding the neurobiological underpinnings of impairments in memory following long-term cannabis use has not been consistent. Furthermore, to our knowledge none of the studies published to date have specifically investigated whether brain function differed between cannabis users and non-users while learning new information as estimated over repeated trials. Therefore, we aimed to investigate this.MethodsTwenty-one predominantly cannabis users (CU) who started using cannabis during adolescence and 21 healthy non-using controls (NU), completed a block design verbal paired associates learning task whilst undergoing functional Magnetic Resonance Imaging. The task required participants to learn and recall a set of word-pairs over 4 repeated trials. We examined the interaction between repetition and group (CU vs NU) on brain activation during encoding and recall condition using non-parametric repeated measures analysis of variance.ResultsThere was no significant difference in total recall score between CU and NU. However, there was a significant effect of repetition (p<0.001) on recall score, suggesting that there was a significant improvement in recall score over repeated trials across the two groups of participants. Furthermore, there was a significant interaction between repetition and group on recall score such that the change in recall score over repeated trials significantly differed (p =0.032) between the CU and NU groups. This was associated with a significant interaction (p =0.009) between group and repetition on activation in the midbrain bilaterally, extending to the, parahippocampus, caudate and cingulate gyrus during the encoding condition. There was greater engagement of these regions in CU than in NU over repeated encoding trials.DiscussionThese results suggest that verbal learning is slower and more effortful requiring greater engagement of critical brain areas involved in learning in cannabis users compared to non-users.

Brain Structural Covariance Network Topology in Remitted Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a prevalent, chronic disorder with high psychiatric morbidity; however, a substantial portion of affected individuals experience remission after onset. Alterations in brain network topology derived from cortical thickness correlations are associated with PTSD, but the effects of remitted symptoms on network topology remain essentially unexplored. In this cross-sectional study, US military veterans (N = 317) were partitioned into three diagnostic groups, current PTSD (CURR-PTSD, N = 101), remitted PTSD with lifetime but no current PTSD (REMIT-PTSD, N = 35), and trauma-exposed controls (CONTROL, n = 181). Cortical thickness was assessed for 148 cortical regions (nodes) and suprathreshold interregional partial correlations across subjects constituted connections (edges) in each group. Four centrality measures were compared with characterize between-group differences. The REMIT-PTSD and CONTROL groups showed greater centrality in left frontal pole than the CURR-PTSD group. The REMIT-PTSD group showed greater centrality in right subcallosal gyrus than the other two groups. Both REMIT-PTSD and CURR-PTSD groups showed greater centrality in right superior frontal sulcus than CONTROL group. The centrality in right subcallosal gyrus, left frontal pole, and right superior frontal sulcus may play a role in remission, current symptoms, and PTSD history, respectively. The network centrality changes in critical brain regions and structural networks are associated with remitted PTSD, which typically coincides with enhanced functional behaviors, better emotion regulation, and improved cognitive processing. These brain regions and associated networks may be candidates for developing novel therapies for PTSD. Longitudinal work is needed to characterize vulnerability to chronic PTSD, and resilience to unremitting PTSD.

Alterations of White Matter Integrity and Hippocampal Functional Connectivity in Type 2 Diabetes Without Mild Cognitive Impairment.

Aims: To investigate the white matter (WM) integrity and hippocampal functional connectivity (FC) in type 2 diabetes mellitus (T2DM) patients without mild cognitive impairment (MCI) by using diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively.Methods: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC) were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS) combining region of interests (ROIs) analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), λ1 and λ23) and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Brain volumes were also evaluated among these participants.Results: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC). Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR) and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex.Conclusions: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated.Highlights -T2DM patients without MCI demonstrated no obvious brain volume decrease.-Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients.-Despite no MCI in T2DM patients, decreased functional connectivity between hippocampal region and some critical brain regions were detected.-The alterations in hippocampal functional connectivity were closely associated with those of the white matter structures in T2DM patients.This trial was registered to ClinicalTrials.gov (NCT02420470, https://www.clinicaltrials.gov/).

Relationships between markers of neurologic and endothelial injury during critical illness and long-term cognitive impairment and disability.

Neurologic and endothelial injury biomarkers are associated with prolonged delirium during critical illness and may reflect injury pathways that lead to poor long-term outcomes. We hypothesized that blood-brain barrier (BBB), neuronal, and endothelial injury biomarkers measured during critical illness are associated with cognitive impairment and disability after discharge. We enrolled adults with respiratory failure and/or shock and measured plasma concentrations of BBB (S100B), neuronal (UCHL1, BDNF), and endothelial (E-selectin, PAI-1) injury markerswithin 72h of ICU admission. At 3 and 12months post-discharge, we assessed participants' global cognition, executive function, and activities of daily living (ADL). We used multivariable regression to determine whether biomarkers were associated with outcomes after adjusting for relevant demographic and acute illness covariates. Our study included 419 survivors of critical illness with median age 59years and APACHE II score 25. Higher S100B was associated with worse global cognition at 3 and 12months (P = 0.008; P = 0.01). UCHL1 was nonlinearly associated with global cognition at 3months (P = 0.02). Higher E-selectin was associated with worse global cognition (P = 0.006 at 3months; P = 0.06 at 12months). BDNF and PAI-1 were not associated with global cognition. No biomarkers were associated with executive function. Higher S100B (P = 0.05) and E-selectin (P = 0.02) were associated with increased disability in ADLs at 3months. S100B, a marker of BBB and/or astrocyte injury, and E-selectin, an adhesion molecule and marker of endothelial injury, are associated with long-term cognitive impairment after critical illness, findings that may reflect mechanisms of critical illness brain injury.

Metabotropic glutamate receptor 5 tracer [18F]-FPEB displays increased binding potential in postcentral gyrus and cerebellum of male individuals with autism: a pilot PET study

BackgroundAutism is a neurodevelopmental disorder that is first manifested during early childhood. Postmortem experiments have identified significantly elevated expression of metabotropic glutamate receptor 5 (mGluR5) in cerebellar vermis and prefrontal cortex of individuals with autism.MethodsIn the current study we employed the mGluR5 tracer [18F]-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([18F]-FPEB) to quantify mGluR5 binding in vivo in adults with autism vs. healthy controls using positron emission tomography (PET).ResultsWe identified significantly higher [18F]-FPEB binding potential in the postcentral gyrus and cerebellum of individuals with autism. There was a significant negative correlation between age and [18F]-FPEB binding potential in the cerebellum but not in the postcentral gyrus. In the precuneus, [18F]-FPEB binding potential correlated positively with the lethargy subscale score for the Aberrant Behavioral Checklist (ABC). In cerebellum, there were significant negative correlations between [18F]-FPEB binding potential and ABC total score, ABC hyperactivity subscale score, and the ABC inappropriate speech subscale score.ConclusionsThese novel findings demonstrate for the first time that mGluR5 binding is altered in critical brain areas of subjects with autism, suggesting abnormal glutamate signaling in these regions. Finally, the correlations between altered [18F]-FPEB binding potential in the cerebellum and precuneus suggest that some autistic symptoms may be influenced by abnormal glutamate signaling.

Trans-venous embolization of a basal ganglia ruptured arteriovenous malformation with open surgical arterial control: A hybrid technique

Treatment of ruptured deep-seated arteriovenous malformations is challenging and associated with elevated risks. This is due to the proximity or involvement of critical brain structures and the specifically fine and delicate angioarchitecture of these lesions, making both endovascular and surgical access technically complicated. We present the advantages of a true combined, open surgical and endovascular transvenous approach in a hybrid operating room. The technique may overcome in part the difficulties and may improve safety and risk related concerns.

Hippocampal area CA2: an emerging modulatory gateway in the hippocampal circuit.

The hippocampus is a critical brain region for the formation of declarative memories. While social memory had long been attributed to be a function of the hippocampus, it is only of late that the area CA2 of the hippocampus was demarcated as essential for social memory formation. In addition to this distinct role, CA2 possesses unique molecular, structural and physiological characteristics compared to the other CA regions-CA1 and CA3, and the dentate gyrus (DG). CA2 pyramidal neurons are positioned at a location between CA1 and CA3, receiving inputs from CA3 and DG, in addition to forming a powerful disynaptic circuit with direct input from the entorhinal cortical layer II neurons. CA2 also receives direct inputs from the hypothalamic regions and displays a unique expression pattern for receptors for neuromodulators. The location, inputs, and molecular signatures of the area CA2 point to the possibility that CA2 serves as a modulatory gateway that processes information from the entorhinal cortex and CA3, before relaying them onto CA1, the major output of the hippocampus. This review discusses recent findings regarding plasticity and neuromodulation in the CA2 region of the hippocampus, and how this may have the potential to influence plasticity in connecting circuits, and thereby memory and behaviour.

Controlling the Temporal Structure of Brain Oscillations by Focused Attention Meditation.

Our focus of attention naturally fluctuates between different sources of information even when we desire to focus on a single object. Focused attention (FA) meditation is associated with greater control over this process, yet the neuronal mechanisms underlying this ability are not entirely understood. Here, we hypothesize that the capacity of attention to transiently focus and swiftly change relates to the critical dynamics emerging when neuronal systems balance at a point of instability between order and disorder. In FA meditation, however, the ability to stay focused is trained, which may be associated with a more homogeneous brain state. To test this hypothesis, we applied analytical tools from criticality theory to EEG in meditation practitioners and meditation‐naïve participants from two independent labs. We show that in practitioners—but not in controls—FA meditation strongly suppressed long‐range temporal correlations (LRTC) of neuronal oscillations relative to eyes‐closed rest with remarkable consistency across frequency bands and scalp locations. The ability to reduce LRTC during meditation increased after one year of additional training and was associated with the subjective experience of fully engaging one's attentional resources, also known as absorption. Sustained practice also affected normal waking brain dynamics as reflected in increased LRTC during an eyes‐closed rest state, indicating that brain dynamics are altered beyond the meditative state. Taken together, our findings suggest that the framework of critical brain dynamics is promising for understanding neuronal mechanisms of meditative states and, specifically, we have identified a clear electrophysiological correlate of the FA meditation state.

Pharmacosynthetic Deconstruction of Sleep-Wake Circuits in the Brain.

Over the past decade, basic sleep research investigating the circuitry controlling sleep and wakefulness has been boosted by pharmacosynthetic approaches, including chemogenetic techniques using designed receptors exclusively activated by designer drugs (DREADD). DREADD offers a series of tools that selectively control neuronal activity as a way to probe causal relationship between neuronal sub-populations and the regulation of the sleep-wake cycle. Following the path opened by optogenetics, DREADD tools applied to discrete neuronal sub-populations in numerous brain areas quickly made their contribution to the discovery and the expansion of our understanding of critical brain structures involved in a wide variety of behaviors and in the control of vigilance state architecture.

Prebiotic Effect of Fructooligosaccharides from Morinda officinalis on Alzheimer's Disease in Rodent Models by Targeting the Microbiota-Gut-Brain Axis.

Gut microbiota influences the central nervous system disorders such as Alzheimer’s disease (AD). The prebiotics and probiotics can improve the host cognition. A previous study demonstrated that fructooligosaccharides from Morinda officinalis (OMO) exert effective memory improvements in AD-like animals, thereby considered as potential prebiotics; however, the underlying mechanism still remains enigma. Thus, the present study investigated whether OMO is effective in alleviating AD by targeting the microbiota-gut-brain axis. OMO was administered in rats with AD-like symptoms (D-galactose- and Aβ1-42-induced deficient rats). Significant and systematic deterioration in AD-like animals were identified, including learning and memory abilities, histological changes, production of cytokines, and microbial community shifts. Behavioral experiments demonstrated that OMO administration can ameliorate the learning and memory abilities in both AD-like animals significantly. AD parameters showed that OMO administration cannot only improve oxidative stress and inflammation disorder, but also regulate the synthesis and secretion of neurotransmitter. Histological changes indicated that OMO administration ameliorates the swelling of brain tissues, neuronal apoptosis, and down-regulation of the expression of AD intracellular markers (Tau and Aβ1-42). 16S rRNA sequencing of gut microbiota indicated that OMO administration maintains the diversity and stability of the microbial community. In addition, OMO regulated the composition and metabolism of gut microbiota in inflammatory bowel disease (IBD) mice model treated by overdosed antibiotics and thus showed the prebiotic potential. Moreover, gut microbiota plays a major role in neurodevelopment, leading to alterations in gene expression in critical brain and intestinal regions, thereby resulting in perturbation to the programming of normal cognitive behaviors. Taken together, our findings suggest that the therapeutic effect of the traditional medicine, M. officinalis, on various neurological diseases such as AD, is at least partially contributed by its naturally occurring chemical constituent, OMO, via modulating the interaction between gut ecology and brain physiology.

Brain hubs in lesion models: Predicting functional network topology with lesion patterns in patients

Various important topological properties of healthy brain connectome have recently been identified. However, the manner in which brain lesion changes the functional network topology is unknown. We examined how critical specific brain areas are in the maintenance of network topology using multivariate support vector regression analysis on brain structural and resting-state functional imaging data in 96 patients with brain damages. Patients’ cortical lesion distribution patterns could significantly predict the functional network topology and a set of regions with significant weights in the prediction models were identified as “lesion hubs”. Intriguingly, we found two different types of lesion hubs, whose lesions associated with changes of network topology towards relatively different directions, being either more integrated (global) or more segregated (local), and correspond to hubs identified in healthy functional network in complex manners. Our results pose further important questions about the potential dynamics of the functional brain network after brain damage.

Neuroendoscopy Adapter Module Development for Better Brain Tumor Image Visualization

The issue of brain magnetic resonance image exploration together with classification receives a significant awareness in recent years. Indeed, various computer-aided-diagnosis solutions were suggested to support radiologist in decision-making. In this circumstance, adequate image classification is extremely required as it is the most common critical brain tumors which often develop from subdural hematoma cells, which might be common type in adults. In healthcare milieu, brain MRIs are intended for identification of tumor. In this regard, various computerized diagnosis systems were suggested to help medical professionals in clinical decision-making. As per recent problems, Neuroendoscopy is the gold standard intended for discovering brain tumors; nevertheless, typical Neuroendoscopy can certainly overlook ripped growths. Neuroendoscopy is a minimally-invasive surgical procedure in which the neurosurgeon removes the tumor through small holes in the skull or through the mouth or nose. Neuroendoscopy enables neurosurgeons to access areas of the brain that cannot be reached with traditional surgery to remove the tumor without cutting or harming other parts of the skull. We focused on finding out whether or not visual images of tumor ripped lesions ended up being much better by auto fluorescence image resolution as well as narrow-band image resolution graphic evaluation jointly with the latest neuroendoscopy technique. Also, within the last several years, pathology labs began to proceed in the direction of an entirely digital workflow, using the electronic slides currently being the key element of this technique. Besides lots of benefits regarding storage as well as exploring capabilities with the image information, among the benefits of electronic slides is that they can help the application of image analysis approaches which seek to develop quantitative attributes to assist pathologists in their work. However, systems also have some difficulties in execution and handling. Hence, such conventional method needs automation. We developed and employed to look for the targeted importance along with uncovering the best-focused graphic position by way of aliasing search method incorporated with new Neuroendoscopy Adapter Module (NAM) technique.

Two critical brain networks for generation and combination of remote associations.

Recent functional imaging findings in humans indicate that creativity relies on spontaneous and controlled processes, possibly supported by the default mode and the fronto-parietal control networks, respectively. Here, we examined the ability to generate and combine remote semantic associations, in relation to creative abilities, in patients with focal frontal lesions. Voxel-based lesion-deficit mapping, disconnection-deficit mapping and network-based lesion-deficit approaches revealed critical prefrontal nodes and connections for distinct mechanisms related to creative cognition. Damage to the right medial prefrontal region, or its potential disrupting effect on the default mode network, affected the ability to generate remote ideas, likely by altering the organization of semantic associations. Damage to the left rostrolateral prefrontal region and its connections, or its potential disrupting effect on the left fronto-parietal control network, spared the ability to generate remote ideas but impaired the ability to appropriately combine remote ideas. Hence, the current findings suggest that damage to specific nodes within the default mode and fronto-parietal control networks led to a critical loss of verbal creative abilities by altering distinct cognitive mechanisms.

Put down that smartphone and read to me!

Shared reading between a mother and child is known to benefit that toddler's cognition, social and emotional development, and brain growth. But just what happens inside the brain? To answer this, Hutton et al provide a rather novel, cross-sectional study of 22 low-socioeconomic status mothers and their 4-year-old girls, who completed a functional MRI using an established story-listening task, followed by videotaped observation of an uncoached mother-daughter reading session of the same age-appropriate picture book. Shared-reading scores were positively correlated with functional MRI activation of left frontal and temporal lobes plus the anterior insula, parahippocampus, and putamen. In the reading sessions, only 6 of 22 mother-child dyads shared reading spontaneously without an external prompt, while 10 more required a prompt by the research coordinator. Six did not read at all, due to maternal distraction usually by a smartphone. Shared reading quality scores were significantly negatively correlated with maternal distraction by smartphones. Maternal shared reading experience plays an important role in development of emergent literacy skills for young children. This joint task is associated with brain activation of key language structures, which can be followed by functional MRI. One might wonder whether these same critical brain structures are activated in the child who “interacts” alone with a book on a computer, tablet, or smartphone. Most certainly, a parent more preoccupied with operating a smartphone than interacting with his child adversely affects intellectual development. Article page 204 ▶ Shared Reading Quality and Brain Activation during Story Listening in Preschool-Age ChildrenThe Journal of PediatricsVol. 191PreviewTo explore the relationship between maternal shared reading quality (verbal interactivity and engagement) and brain function during story listening in at-risk, preschool-age children, in the context of behavioral evidence and American Academy of Pediatrics, recommendations. Full-Text PDF