Maternal brain response to own baby-cry is affected by cesarean section delivery

PubMed Central

Swain, James E.; Tasgin, Esra; Mayes, Linda C.; Feldman, Ruth; Constable, R. Todd; Leckman, James F.

2011-01-01

A range of early circumstances surrounding the birth of a child affects peripartum hormones, parental behavior and infant wellbeing. One of these factors, which may lead to postpartum depression, is the mode of delivery: vaginal delivery (VD) or cesarean section delivery (CSD). To test the hypothesis that CSD mothers would be less responsive to own baby-cry stimuli than VD mothers in the immediate postpartum period, we conducted functional magnetic resonance imaging, 2–4 weeks after delivery, of the brains of six mothers who delivered vaginally and six who had an elective CSD. VD mothers’ brains were significantly more responsive than CSD mothers’ brains to their own baby-cry in the superior and middle temporal gyri, superior frontal gyrus, medial fusiform gyrus, superior parietal lobe, as well as regions of the caudate, thalamus, hypothalamus, amygdala and pons. Also, within preferentially active regions of VD brains, there were correlations across all 12 mothers with out-of-magnet variables. These include correlations between own baby-cry responses in the left and right lenticular nuclei and parental preoccupations (r = .64, p < .05 and .67, p < .05 respectively), as well as in the superior frontal cortex and Beck depression inventory (r = .78, p < .01). First this suggests that VD mothers are more sensitive to own baby-cry than CSD mothers in the early postpartum in sensory processing, empathy, arousal, motivation, reward and habit-regulation circuits. Second, independent of mode of delivery, parental worries and mood are related to specific brain activations in response to own baby-cry. PMID:18771508

Early detection of consciousness in patients with acute severe traumatic brain injury.

PubMed

Edlow, Brian L; Chatelle, Camille; Spencer, Camille A; Chu, Catherine J; Bodien, Yelena G; O'Connor, Kathryn L; Hirschberg, Ronald E; Hochberg, Leigh R; Giacino, Joseph T; Rosenthal, Eric S; Wu, Ona

2017-09-01

See Schiff (doi:10.1093/awx209) for a scientific commentary on this article. Patients with acute severe traumatic brain injury may recover consciousness before self-expression. Without behavioural evidence of consciousness at the bedside, clinicians may render an inaccurate prognosis, increasing the likelihood of withholding life-sustaining therapies or denying rehabilitative services. Task-based functional magnetic resonance imaging and electroencephalography techniques have revealed covert consciousness in the chronic setting, but these techniques have not been tested in the intensive care unit. We prospectively enrolled 16 patients admitted to the intensive care unit for acute severe traumatic brain injury to test two hypotheses: (i) in patients who lack behavioural evidence of language expression and comprehension, functional magnetic resonance imaging and electroencephalography detect command-following during a motor imagery task (i.e. cognitive motor dissociation) and association cortex responses during language and music stimuli (i.e. higher-order cortex motor dissociation); and (ii) early responses to these paradigms are associated with better 6-month outcomes on the Glasgow Outcome Scale-Extended. Patients underwent functional magnetic resonance imaging on post-injury Day 9.2 ± 5.0 and electroencephalography on Day 9.8 ± 4.6. At the time of imaging, behavioural evaluation with the Coma Recovery Scale-Revised indicated coma (n = 2), vegetative state (n = 3), minimally conscious state without language (n = 3), minimally conscious state with language (n = 4) or post-traumatic confusional state (n = 4). Cognitive motor dissociation was identified in four patients, including three whose behavioural diagnosis suggested a vegetative state. Higher-order cortex motor dissociation was identified in two additional patients. Complete absence of responses to language, music and motor imagery was only observed in coma patients. In patients with behavioural evidence

Dynamic contrast-enhanced MR imaging pharmacokinetic parameters as predictors of treatment response of brain metastases in patients with lung cancer.

PubMed

Kuchcinski, Grégory; Le Rhun, Emilie; Cortot, Alexis B; Drumez, Elodie; Duhal, Romain; Lalisse, Maxime; Dumont, Julien; Lopes, Renaud; Pruvo, Jean-Pierre; Leclerc, Xavier; Delmaire, Christine

2017-09-01

To determine the diagnostic accuracy of pharmacokinetic parameters measured by dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in predicting the response of brain metastases to antineoplastic therapy in patients with lung cancer. Forty-four consecutive patients with lung cancer, harbouring 123 newly diagnosed brain metastases prospectively underwent conventional 3-T MRI at baseline (within 1 month before treatment), during the early (7-10 weeks) and midterm (5-7 months) post-treatment period. An additional DCE MRI sequence was performed during baseline and early post-treatment MRI to evaluate baseline pharmacokinetic parameters (K trans , k ep , v e , v p ) and their early variation (∆K trans , ∆k ep , ∆v e , ∆v p ). The objective response was judged by the volume variation of each metastasis from baseline to midterm MRI. ROC curve analysis determined the best DCE MRI parameter to predict the objective response. Baseline DCE MRI parameters were not associated with the objective response. Early ∆K trans , ∆v e and ∆v p were significantly associated with the objective response (p = 0.02, p = 0.001 and p = 0.02, respectively). The best predictor of objective response was ∆v e with an area under the curve of 0.93 [95% CI = 0.87, 0.99]. DCE MRI and early ∆v e may be a useful tool to predict the objective response of brain metastases in patients with lung cancer. • DCE MRI could predict the response of brain metastases from lung cancer • ∆v e was the best predictor of response • DCE MRI could be used to individualize patients' follow-up.

Hypobaric Hypoxia Exacerbates the Neuroinflammatory Response to Traumatic Brain Injury

PubMed Central

Goodman, Michael D.; Makley, Amy T.; Huber, Nathan L.; Clarke, Callisia N.; Friend, Lou Ann W.; Schuster, Rebecca M.; Bailey, Stephanie R.; Barnes, Stephen L.; Dorlac, Warren C.; Johannigman, Jay A.; Lentsch, Alex B.; Pritts, Timothy A.

2015-01-01

Objective To determine the inflammatory effects of time-dependent exposure to the hypobaric environment of simulated aeromedical evacuation following traumatic brain injury (TBI). Methods Mice were subjected to a blunt TBI or sham injury. Righting reflex response (RRR) time was assessed as an indicator of neurologic recovery. Three or 24 h (Early and Delayed groups, respectively) after TBI, mice were exposed to hypobaric flight conditions (Fly) or ground-level control (No Fly) for 5 h. Arterial blood gas samples were obtained from all groups during simulated flight. Serum and cortical brain samples were analyzed for inflammatory cytokines after flight. Neuron specific enolase (NSE) was measured as a serum biomarker of TBI severity. Results TBI resulted in prolonged RRR time compared with sham injury. After TBI alone, serum levels of interleukin-6 (IL-6) and keratinocyte-derived chemokine (KC) were increased by 6 h post-injury. Simulated flight significantly reduced arterial oxygen saturation levels in the Fly group. Post-injury altitude exposure increased cerebral levels of IL-6 and macrophage inflammatory protein-1α (MIP-1α), as well as serum NSE in the Early but not Delayed Flight group compared to ground-level controls. Conclusions The hypobaric environment of aero-medical evacuation results in significant hypoxia. Early, but not delayed, exposure to a hypobaric environment following TBI increases the neuroinflammatory response to injury and the severity of secondary brain injury. Optimization of the post-injury time to fly using serum cytokine and biomarker levels may reduce the potential secondary cerebral injury induced by aeromedical evacuation. PMID:20850781

Face and location processing in children with early unilateral brain injury.

PubMed

Paul, Brianna; Appelbaum, Mark; Carapetian, Stephanie; Hesselink, John; Nass, Ruth; Trauner, Doris; Stiles, Joan

2014-07-01

Human visuospatial functions are commonly divided into those dependent on the ventral visual stream (ventral occipitotemporal regions), which allows for processing the 'what' of an object, and the dorsal visual stream (dorsal occipitoparietal regions), which allows for processing 'where' an object is in space. Information about the development of each of the two streams has been accumulating, but very little is known about the effects of injury, particularly very early injury, on this developmental process. Using a set of computerized dorsal and ventral stream tasks matched for stimuli, required response, and difficulty (for typically-developing individuals), we sought to compare the differential effects of injury to the two systems by examining performance in individuals with perinatal brain injury (PBI), who present with selective deficits in visuospatial processing from a young age. Thirty participants (mean=15.1 years) with early unilateral brain injury (15 right hemisphere PBI, 15 left hemisphere PBI) and 16 matched controls participated. On our tasks children with PBI performed more poorly than controls (lower accuracy and longer response times), and this was particularly prominent for the ventral stream task. Lateralization of PBI was also a factor, as the dorsal stream task did not seem to be associated with lateralized deficits, with both PBI groups showing only subtle decrements in performance, while the ventral stream task elicited deficits from RPBI children that do not appear to improve with age. Our findings suggest that early injury results in lesion-specific visuospatial deficits that persist into adolescence. Further, as the stimuli used in our ventral stream task were faces, our findings are consistent with what is known about the neural systems for face processing, namely, that they are established relatively early, follow a comparatively rapid developmental trajectory (conferring a vulnerability to early insult), and are biased toward the right

Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes.

PubMed

Renier, Nicolas; Adams, Eliza L; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E; Kadiri, Lolahon; Umadevi Venkataraju, Kannan; Zhou, Yu; Wang, Victoria X; Tang, Cheuk Y; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

2016-06-16

Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization, and quantification of the activity of all neurons across the entire brain, which has not, to date, been achieved in the mammalian brain. We introduce a pipeline for high-speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Last, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping of brain activity by automated volume analysis of immediate early genes

PubMed Central

Renier, Nicolas; Adams, Eliza L.; Kirst, Christoph; Wu, Zhuhao; Azevedo, Ricardo; Kohl, Johannes; Autry, Anita E.; Kadiri, Lolahon; Venkataraju, Kannan Umadevi; Zhou, Yu; Wang, Victoria X.; Tang, Cheuk Y.; Olsen, Olav; Dulac, Catherine; Osten, Pavel; Tessier-Lavigne, Marc

2016-01-01

Summary Understanding how neural information is processed in physiological and pathological states would benefit from precise detection, localization and quantification of the activity of all neurons across the entire brain, which has not to date been achieved in the mammalian brain. We introduce a pipeline for high speed acquisition of brain activity at cellular resolution through profiling immediate early gene expression using immunostaining and light-sheet fluorescence imaging, followed by automated mapping and analysis of activity by an open-source software program we term ClearMap. We validate the pipeline first by analysis of brain regions activated in response to Haloperidol. Next, we report new cortical regions downstream of whisker-evoked sensory processing during active exploration. Lastly, we combine activity mapping with axon tracing to uncover new brain regions differentially activated during parenting behavior. This pipeline is widely applicable to different experimental paradigms, including animal species for which transgenic activity reporters are not readily available. PMID:27238021

Temporal orienting precedes intersensory attention and has opposing effects on early evoked brain activity.

PubMed

Keil, Julian; Pomper, Ulrich; Feuerbach, Nele; Senkowski, Daniel

2017-03-01

Intersensory attention (IA) describes the process of directing attention to a specific modality. Temporal orienting (TO) characterizes directing attention to a specific moment in time. Previously, studies indicated that these two processes could have opposite effects on early evoked brain activity. The exact time-course and processing stages of both processes are still unknown. In this human electroencephalography study, we investigated the effects of IA and TO on visuo-tactile stimulus processing within one paradigm. IA was manipulated by presenting auditory cues to indicate whether participants should detect visual or tactile targets in visuo-tactile stimuli. TO was manipulated by presenting stimuli block-wise at fixed or variable inter-stimulus intervals. We observed that TO affects evoked activity to visuo-tactile stimuli prior to IA. Moreover, we found that TO reduces the amplitude of early evoked brain activity, whereas IA enhances it. Using beamformer source-localization, we observed that IA increases neural responses in sensory areas of the attended modality whereas TO reduces brain activity in widespread cortical areas. Based on these findings we derive an updated working model for the effects of temporal and intersensory attention on early evoked brain activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Children's Executive Functions: Are They Poorer after Very Early Brain Insult

ERIC Educational Resources Information Center

Anderson, Vicki; Spencer-Smith, Megan; Coleman, Lee; Anderson, Peter; Williams, Jackie; Greenham, Mardee; Leventer, Richard J.; Jacobs, Rani

2010-01-01

Traditionally early brain insult (EBI) has been considered to have better outcome than later injury, consistent with the notion that the young brain is flexible and able to reorganize. Recent research findings question this view, suggesting that EBI might lead to poorer outcome than brain insult at any other age. Exploring this early vulnerability…

Media representations of early human development: protecting, feeding and loving the developing brain.

PubMed

O'Connor, Cliodhna; Joffe, Helene

2013-11-01

The public profile of neurodevelopmental research has expanded in recent years. This paper applies social representations theory to explore how early brain development was represented in the UK print media in the first decade of the 21st century. A thematic analysis was performed on 505 newspaper articles published between 2000 and 2010 that discussed early brain development. Media coverage centred around concern with 'protecting' the prenatal brain (identifying threats to foetal neurodevelopment), 'feeding' the infant brain (indicating the patterns of nutrition that enhance brain development) and 'loving' the young child's brain (elucidating the developmental significance of emotionally nurturing family environments). The media focused almost exclusively on the role of parental action in promoting optimal neurodevelopment, rarely acknowledging wider structural, cultural or political means of supporting child development. The significance of parental care was intensified by deterministic interpretations of critical periods, which implied that inappropriate parental input would produce profound and enduring neurobiological impairments. Neurodevelopmental research was also used to promulgate normative judgements concerning the acceptability of certain gender roles and family contexts. The paper argues that media representations of neurodevelopment stress parental responsibility for shaping a child's future while relegating the contributions of genetic or wider societal factors, and examines the consequences of these representations for society and family life. Copyright © 2012 Elsevier Ltd. All rights reserved.

Bone density and brain atrophy in early Alzheimer's disease.

PubMed

Loskutova, Natalia; Honea, Robyn A; Vidoni, Eric D; Brooks, William M; Burns, Jeffrey M

2009-01-01

Studies suggest a link between bone loss and Alzheimer's disease. To examine bone mineral density (BMD) in early Alzheimer's disease (AD) and its relationship to brain structure and cognition, we evaluated 71 patients with early stage AD (Clinical Dementia Rating (CDR) 0.5 and 1) and 69 non-demented elderly control participants (CDR 0). Measures included whole body BMD by dual energy x-ray absorptiometry (DXA) and normalized whole brain volumes computed from structural MRI scans. Cognition was assessed with a standard neuropsychological test battery. Mean BMD was lower in the early AD group (1.11 +/- 0.13) compared to the non-demented control group (1.16 +/- 0.12, p = 0.02), independent of age, gender, habitual physical activity, smoking, depression, estrogen replacement, and apolipoprotein E4 carrier status. In the early AD group, BMD was related to whole brain volume (b = 0.18, p = 0.03). BMD was also associated with cognitive performance, primarily in tests of memory (logical memory [b = 0.15, p = 0.04], delayed logical memory [b = 0.16, p = 0.02], and the selective reminding task - free recall [b = 0.18, p = 0.009]). BMD is reduced in the earliest clinical stages of AD and associated with brain atrophy and memory decline, suggesting that central mechanisms may contribute to bone loss in early AD.

Early Influences on Brain Architecture: An Interview with Neuroscientist Eric Knudsen. Perspectives

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2006

2006-01-01

Early experience has a powerful and lasting influence on how the brain develops. The physical and chemical conditions that encourage the building of a strong, adaptive brain architecture are present early in life. As brains age, a number of changes lock in the ways information is processed, making it more difficult for the brain to change to other…

Deep brain stimulation effects in dystonia: time course of electrophysiological changes in early treatment.

PubMed

Ruge, Diane; Tisch, Stephen; Hariz, Marwan I; Zrinzo, Ludvic; Bhatia, Kailash P; Quinn, Niall P; Jahanshahi, Marjan; Limousin, Patricia; Rothwell, John C

2011-08-15

Deep brain stimulation to the internal globus pallidus is an effective treatment for primary dystonia. The optimal clinical effect often occurs only weeks to months after starting stimulation. To better understand the underlying electrophysiological changes in this period, we assessed longitudinally 2 pathophysiological markers of dystonia in patients prior to and in the early treatment period (1, 3, 6 months) after deep brain stimulation surgery. Transcranial magnetic stimulation was used to track changes in short-latency intracortical inhibition, a measure of excitability of GABA(A) -ergic corticocortical connections and long-term potentiation-like synaptic plasticity (as a response to paired associative stimulation). Deep brain stimulation remained on for the duration of the study. Prior to surgery, inhibition was reduced and plasticity increased in patients compared with healthy controls. Following surgery and commencement of deep brain stimulation, short-latency intracortical inhibition increased toward normal levels over the following months with the same monotonic time course as the patients' clinical benefit. In contrast, synaptic plasticity changed rapidly, following a nonmonotonic time course: it was absent early (1 month) after surgery, and then over the following months increased toward levels observed in healthy individuals. We postulate that before surgery preexisting high levels of plasticity form strong memories of dystonic movement patterns. When deep brain stimulation is turned on, it disrupts abnormal basal ganglia signals, resulting in the absent response to paired associative stimulation at 1 month. Clinical benefit is delayed because engrams of abnormal movement persist and take time to normalize. Our observations suggest that plasticity may be a driver of long-term therapeutic effects of deep brain stimulation in dystonia. Copyright © 2011 Movement Disorder Society.

Early Brain Vulnerability in Wolfram Syndrome

PubMed Central

Hershey, Tamara; Lugar, Heather M.; Shimony, Joshua S.; Rutlin, Jerrel; Koller, Jonathan M.; Perantie, Dana C.; Paciorkowski, Alex R.; Eisenstein, Sarah A.; Permutt, M. Alan

2012-01-01

Wolfram Syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development. PMID:22792385

Sigmund Freud-early network theories of the brain.

PubMed

Surbeck, Werner; Killeen, Tim; Vetter, Johannes; Hildebrandt, Gerhard

2018-06-01

Since the early days of modern neuroscience, psychological models of brain function have been a key component in the development of new knowledge. These models aim to provide a framework that allows the integration of discoveries derived from the fundamental disciplines of neuroscience, including anatomy and physiology, as well as clinical neurology and psychiatry. During the initial stages of his career, Sigmund Freud (1856-1939), became actively involved in these nascent fields with a burgeoning interest in functional neuroanatomy. In contrast to his contemporaries, Freud was convinced that cognition could not be localised to separate modules and that the brain processes cognition not in a merely serial manner but in a parallel and dynamic fashion-anticipating fundamental aspects of current network theories of brain function. This article aims to shed light on Freud's seminal, yet oft-overlooked, early work on functional neuroanatomy and his reasons for finally abandoning the conventional neuroscientific "brain-based" reference frame in order to conceptualise the mind from a purely psychological perspective.

Brain Responses to Lexical-Semantic Priming in Children At-Risk for Dyslexia

ERIC Educational Resources Information Center

Torkildsen, Janne von Koss; Syversen, Gro; Simonsen, Hanne Gram; Moen, Inger; Lindgren, Magnus

2007-01-01

Deviances in early event-related potential (ERP) components reflecting auditory and phonological processing are well-documented in children at familial risk for dyslexia. However, little is known about brain responses which index processing in other linguistic domains such as lexicon, semantics and syntax in this group. The present study…

Narrative discourse in children with early focal brain injury.

PubMed

Reilly, J S; Bates, E A; Marchman, V A

1998-02-15

Children with early brain damage, unlike adult stroke victims, often go on to develop nearly normal language. However, the route and extent of their linguistic development are still unclear, as is the relationship between lesion site and patterns of delay and recovery. Here we address these questions by examining narratives from children with early brain damage. Thirty children (ages 3:7-10:10) with pre- or perinatal unilateral focal brain damage and their matched controls participated in a storytelling task. Analyses focused on linguistic proficiency and narrative competence. Overall, children with brain damage scored significantly lower than their age-matched controls on both linguistic (morphological and syntactic) indices and those targeting broader narrative qualities. Rather than indicating that children with brain damage fully catch up, these data suggest that deficits in linguistic abilities reassert themselves as children face new linguistic challenges. Interestingly, after age 5, site of lesion does not appear to be a significant factor and the delays we have witnessed do not map onto the lesion profiles observed in adults with analogous brain injuries.

Changes in spontaneous brain activity in early Parkinson's disease.

PubMed

Yang, Hong; Zhou, Xiaohong Joe; Zhang, Min-Ming; Zheng, Xu-Ning; Zhao, Yi-Lei; Wang, Jue

2013-08-09

Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of p<0.05 was determined by AlphaSim and used in statistical analysis. Compared with the healthy controls, the early PD group showed significantly increased ReHo in a number of brain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=-0

Manifestations of early brain recovery associated with abstinence from alcoholism.

PubMed

Bartsch, Andreas J; Homola, György; Biller, Armin; Smith, Stephen M; Weijers, Heinz-Gerd; Wiesbeck, Gerhard A; Jenkinson, Mark; De Stefano, Nicola; Solymosi, László; Bendszus, Martin

2007-01-01

Chronic alcohol abuse results in morphological, metabolic, and functional brain damage which may, to some extent, be reversible with early effects upon abstinence. Although morphometric, spectroscopic, and neuropsychological indicators of cerebral regeneration have been described previously, the overall amount and spatial preference of early brain recovery attained by abstinence and its associations with other indicators of regeneration are not well established. We investigated global and local brain volume changes in a longitudinal two-timepoint study with T1-weighted MRI at admission and after short-term (6-7 weeks) sobriety follow-up in 15 uncomplicated, recently detoxified alcoholics. Volumetric brain gain was related to metabolic and neuropsychological recovery. On admission and after short-term abstinence, structural image evaluation using normalization of atrophy (SIENA), its voxelwise statistical extension to multiple subjects, proton MR spectroscopy (1H-MRS), and neuropsychological tests were applied. Upon short-term sobriety, 1H-MRS levels of cerebellar choline and frontomesial N-acetylaspartate (NAA) were significantly augmented. Automatically detected global brain volume gain amounted to nearly two per cent on average and was spatially significant around the superior vermis, perimesencephalic, periventricular and frontal brain edges. It correlated positively with the percentages of cerebellar and frontomesial choline increase, as detected by 1H-MRS. Moreover, frontomesial NAA gains were associated with improved performance on the d2-test of attention. In 10 age- and gender-matched healthy control subjects, no significant brain volume or metabolite changes were observed. Although cerebral osmotic regulations may occur initially upon sobriety, significant increases of cerebellar choline and frontomesial NAA levels detected at stable brain water integrals and creatine concentrations, serum electrolytes and red blood cell indices in our patient sample

Resilience in mathematics after early brain injury: The roles of parental input and early plasticity.

PubMed

Glenn, Dana E; Demir-Lira, Özlem Ece; Gibson, Dominic J; Congdon, Eliza L; Levine, Susan C

2018-04-01

Children with early focal unilateral brain injury show remarkable plasticity in language development. However, little is known about how early brain injury influences mathematical learning. Here, we examine early number understanding, comparing cardinal number knowledge of typically developing children (TD) and children with pre- and perinatal lesions (BI) between 42 and 50 months of age. We also examine how this knowledge relates to the number words children hear from their primary caregivers early in life. We find that children with BI, are, on average, slightly behind TD children in both cardinal number knowledge and later mathematical performance, and show slightly slower learning rates than TD children in cardinal number knowledge during the preschool years. We also find that parents' "number talk" to their toddlers predicts later mathematical ability for both TD children and children with BI. These findings suggest a relatively optimistic story in which neural plasticity is at play in children's mathematical development following early brain injury. Further, the effects of early number input suggest that intervening to enrich the number talk that children with BI hear during the preschool years could narrow the math achievement gap. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Novel Risk Stratification Score for Predicting Early Distant Brain Failure and Salvage Whole Brain Radiotherapy after Stereotactic Radiosurgery for Brain Metastases

PubMed Central

Press, Robert H.; Prabhu, Roshan S.; Nickleach, Dana C.; Liu, Yuan; Shu, Hui-Kuo G.; Kandula, Shravan; Patel, Kirtesh R.; Curran, Walter J.; Crocker, Ian

2015-01-01

Background The purpose of this study was to evaluate predictors of early distant brain failure (DBF) and salvage whole brain radiotherapy (WBRT) after treatment with stereotactic radiosurgery (SRS) for brain metastases and create a clinically relevant risk score in order to stratify patients’ risk of these events. Methods We reviewed records of 270 patients with brain metastases treated with SRS between 2003-2012. Pre-treatment patient and tumor characteristics were analyzed by univariate and multivariable analyses. Cumulative incidence (CI) of first DBF and salvage WBRT were calculated. Significant factors were used to create a score for stratifying early (6-month) DBF risk. Results No prior WBRT, total lesion volume <1.3 cm3, primary breast cancer or malignant melanoma histology, and multiple metastases (≥2) were found to be significant predictors for early DBF. Each factor was ascribed one point due to similar hazard ratios. Scores of 0-1, 2, and 3-4 were considered low, intermediate, and high risk, respectively. This correlated with 6-month CI of DBF of 16.6%, 28.8%, and 54.4%, respectively (p<0.001). For patients without prior WBRT, the 6-month CI of salvage WBRT by 6-months was 2%, 17.7%, and 25.7%, respectively (p<0.001). Conclusion Early DBF after SRS requiring salvage WBRT remains a significant clinical problem. Patient stratification for early DBF can better inform the decision for initial treatment strategy for brain metastases. The provided risk score may help predict for early DBF and subsequent salvage WBRT if initial SRS is used. External validation is needed prior to clinical implementation. PMID:26242475

Validation of the Early Functional Abilities scale: An assessment of four dimensions in early recovery after traumatic brain injury.

PubMed

Poulsen, Ingrid; Kreiner, Svend; Engberg, Aase W

2018-02-13

The Early Functional Abilities scale assesses the restoration of brain function after brain injury, based on 4 dimensions. The primary objective of this study was to evaluate the validity, objectivity, reliability and measurement precision of the Early Functional Abilities scale by Rasch model item analysis. A secondary objective was to examine the relationship between the Early Functional Abilities scale and the Functional Independence Measurement™, in order to establish the criterion validity of the Early Functional Abilities scale and to compare the sensitivity of measurements using the 2 instruments. The Rasch analysis was based on the assessment of 408 adult patients at admission to sub-acute rehabilitation in Copenhagen, Denmark after traumatic brain injury. The Early Functional Abilities scale provides valid and objective measurement of vegetative (autonomic), facio-oral, sensorimotor and communicative/cognitive functions. Removal of one item from the sensorimotor scale confirmed unidimensionality for each of the 4 subscales, but not for the entire scale. The Early Functional Abilities subscales are sensitive to differences between patients in ranges in which the Functional Independence Measurement™ has a floor effect. The Early Functional Abilities scale assesses the early recovery of important aspects of brain function after traumatic brain injury, but is not unidimensional. We recommend removal of the "standing" item and calculation of summary subscales for the separate dimensions.

Prolonged maternal separation disturbs the serotonergic system during early brain development.

PubMed

Ohta, Ken-Ichi; Miki, Takanori; Warita, Katsuhiko; Suzuki, Shingo; Kusaka, Takashi; Yakura, Tomiko; Liu, Jun-Qian; Tamai, Motoki; Takeuchi, Yoshiki

2014-04-01

Early life stress interrupts brain development through the disturbance of various neurotransmitter and neurotrophic factor activities, but the details remain unclear. In the current study, we focused on the serotonergic system, which plays a critical role in brain development, and examined the time-dependent influence of prolonged maternal separation on male Sprague-Dawley rats. The rats were separated from their dams for 3h twice-daily during postnatal days (PDs) 2-20. The influence of prolonged maternal separation was analyzed on PDs 7, 14, 21, and 28 using HPLC to assess concentrations of serotonin and 5-hydroxyindoleacetic acid and using real-time RT-PCR to measure mRNA expression of the serotonin 1A and 2A receptors in various brain regions. HPLC revealed imbalance between serotonin and 5-hydroxyindoleacetic acid in midbrain raphe nuclei, the amygdala, the hippocampus, and the medial prefrontal cortex (mPFC) on PDs 7 and 14. Furthermore, real-time RT-PCR showed attenuation of mRNA expression of the serotonin 1A receptor in the hippocampus and the mPFC and of the serotonin 2A receptor only in the mPFC on PDs 7 and 14. The observed alterations returned to control levels after maternal separation ended. These findings suggest that the early life stress of prolonged maternal separation disturbs the serotonergic system during a crucial period of brain development, which might in part be responsible for emotional abnormalities later in life. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Starting Smart: How Early Experiences Affect Brain Development. Second Edition.

ERIC Educational Resources Information Center

Hawley, Theresa

Based on recent research, it is now believed that brain growth is highly dependent upon children's early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring the connections among neurons. The forming and breaking of…

Loss of serum IGF-I input to the brain as an early biomarker of disease onset in Alzheimer mice

PubMed Central

Trueba-Sáiz, A; Cavada, C; Fernandez, A M; Leon, T; González, D A; Fortea Ormaechea, J; Lleó, A; Del Ser, T; Nuñez, A; Torres-Aleman, I

2013-01-01

Circulating insulin-like growth factor I (IGF-I) enters the brain and promotes clearance of amyloid peptides known to accumulate in Alzheimer's disease (AD) brains. Both patients and mouse models of AD show decreased level of circulating IGF-I enter the brain as evidenced by a lower ratio of cerebrospinal fluid/plasma IGF-I. Importantly, in presymptomatic AD mice this reduction is already manifested as a decreased brain input of serum IGF-I in response to environmental enrichment. To explore a potential diagnostic use of this early loss of IGF-I input, we monitored electrocorticogram (ECG) responses to systemic IGF-I in mice. Whereas control mice showed enhanced ECG activity after IGF-I, presymptomatic AD mice showed blunted ECG responses. Because nonhuman primates showed identically enhanced electroencephalogram (EEG) activity in response to systemic IGF-I, loss of the EEG signature of serum IGF-I may be exploited as a disease biomarker in AD patients. PMID:24301648

Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury.

PubMed

Yang, Lianhong; Yang, Jianhua; Li, Guoqian; Li, Yi; Wu, Rong; Cheng, Jinping; Tang, Yamei

2017-03-01

The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.

DEVELOPMENTAL CHANGES IN SEROTONIN SIGNALING: IMPLICATIONS FOR EARLY BRAIN FUNCTION, BEHAVIOR AND ADAPTATION

PubMed Central

BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.

2017-01-01

The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950

Starting Smart: How Early Experiences Affect Brain Development. An Ounce of Prevention Fund Paper.

ERIC Educational Resources Information Center

Ounce of Prevention Fund.

Recent research has provided great insight into the impact of early experience on brain development. It is now believed that brain growth is highly dependent upon early experiences. Neurons allow communication and coordinated functioning among various brain areas. Brain development after birth consists of an ongoing process of wiring and rewiring…

Normal variation in early parental sensitivity predicts child structural brain development.

PubMed

Kok, Rianne; Thijssen, Sandra; Bakermans-Kranenburg, Marian J; Jaddoe, Vincent W V; Verhulst, Frank C; White, Tonya; van IJzendoorn, Marinus H; Tiemeier, Henning

2015-10-01

Early caregiving can have an impact on brain structure and function in children. The influence of extreme caregiving experiences has been demonstrated, but studies on the influence of normal variation in parenting quality are scarce. Moreover, no studies to date have included the role of both maternal and paternal sensitivity in child brain maturation. This study examined the prospective relation between mothers' and fathers' sensitive caregiving in early childhood and brain structure later in childhood. Participants were enrolled in a population-based prenatal cohort. For 191 families, maternal and paternal sensitivity was repeatedly observed when the child was between 1 year and 4 years of age. Head circumference was assessed at 6 weeks, and brain structure was assessed using magnetic resonance imaging (MRI) measurements at 8 years of age. Higher levels of parental sensitivity in early childhood were associated with larger total brain volume (adjusted β = 0.15, p = .01) and gray matter volume (adjusted β = 0.16, p = .01) at 8 years, controlling for infant head size. Higher levels of maternal sensitivity in early childhood were associated with a larger gray matter volume (adjusted β = 0.13, p = .04) at 8 years, independent of infant head circumference. Associations with maternal versus paternal sensitivity were not significantly different. Normal variation in caregiving quality is related to markers of more optimal brain development in children. The results illustrate the important role of both mothers and fathers in child brain development. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Plasticity following early-life brain injury: Insights from quantitative MRI.

PubMed

Fiori, Simona; Guzzetta, Andrea

2015-03-01

Over the last decade, the application of novel advanced neuroimaging techniques to study congenital brain damage has provided invaluable insights into the mechanisms underlying early neuroplasticity. The concept that is clearly emerging, both from human and nun-human studies, is that functional reorganization in the immature brain is substantially different from that of the more mature, developed brain. This applies to the reorganization of language, the sensorimotor system, and the visual system. The rapid implementation and development of higher order imaging methods will offer increased, currently unavailable knowledge about the specific mechanisms of cerebral plasticity in infancy, which is essential to support the development of early therapeutic interventions aimed at supporting and enhancing functional reorganization during a time of greatest potential brain plasticity. Copyright © 2015. Published by Elsevier Inc.

Linking Brain Principles to High-Quality Early Childhood Education

ERIC Educational Resources Information Center

Rushton, Stephen; Juola-Rushton, Anne

2011-01-01

Many educators are already knowledgeable about and skilled in best practices. And much of what is happening in developmentally appropriate programs exemplifies "brain compatible" practices. Being educated in the connections between best practices and brain compatibility is an important part of the knowledge base of early childhood educators. Just…

Repeated diffusion MRI reveals earliest time point for stratification of radiotherapy response in brain metastases

NASA Astrophysics Data System (ADS)

Mahmood, Faisal; Johannesen, Helle H.; Geertsen, Poul; Hansen, Rasmus H.

2017-04-01

An imaging biomarker for early prediction of treatment response potentially provides a non-invasive tool for better prognostics and individualized management of the disease. Radiotherapy (RT) response is generally related to changes in gross tumor volume manifesting months later. In this prospective study we investigated the apparent diffusion coefficient (ADC), perfusion fraction and pseudo diffusion coefficient derived from diffusion weighted MRI as potential early biomarkers for radiotherapy response of brain metastases. It was a particular aim to assess the optimal time point for acquiring the DW-MRI scan during the course of treatment, since to our knowledge this important question has not been addressed directly in previous studies. Twenty-nine metastases (N  =  29) from twenty-one patients, treated with whole-brain fractionated external beam RT were analyzed. Patients were scanned with a 1 T MRI system to acquire DW-, T2*W-, T2W- and T1W scans, before start of RT, at each fraction and at follow up two to three months after RT. The DW-MRI parameters were derived using regions of interest based on high b-value images (b  =  800 s mm-2). Both volumetric and RECIST criteria were applied for response evaluation. It was found that in non-responding metastases the mean ADC decreased and in responding metastases it increased. The volume based response proved to be far more consistently predictable by the ADC change found at fraction number 7 and later, compared to the linear response (RECIST). The perfusion fraction and pseudo diffusion coefficient did not show sufficient prognostic value with either response assessment criteria. In conclusion this study shows that the ADC derived using high b-values may be a reliable biomarker for early assessment of radiotherapy response for brain metastases patients. The earliest response stratification can be achieved using two DW-MRI scans, one pre-treatment and one at treatment day 7-9 (equivalent to 21 Gy).

Early Alzheimer's and Parkinson's disease pathology in urban children: Friend versus Foe responses--it is time to face the evidence.

PubMed

Calderón-Garcidueñas, Lilian; Franco-Lira, Maricela; Mora-Tiscareño, Antonieta; Medina-Cortina, Humberto; Torres-Jardón, Ricardo; Kavanaugh, Michael

2013-01-01

Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health.

Infants' brain responses to speech suggest analysis by synthesis.

PubMed

Kuhl, Patricia K; Ramírez, Rey R; Bosseler, Alexis; Lin, Jo-Fu Lotus; Imada, Toshiaki

2014-08-05

Historic theories of speech perception (Motor Theory and Analysis by Synthesis) invoked listeners' knowledge of speech production to explain speech perception. Neuroimaging data show that adult listeners activate motor brain areas during speech perception. In two experiments using magnetoencephalography (MEG), we investigated motor brain activation, as well as auditory brain activation, during discrimination of native and nonnative syllables in infants at two ages that straddle the developmental transition from language-universal to language-specific speech perception. Adults are also tested in Exp. 1. MEG data revealed that 7-mo-old infants activate auditory (superior temporal) as well as motor brain areas (Broca's area, cerebellum) in response to speech, and equivalently for native and nonnative syllables. However, in 11- and 12-mo-old infants, native speech activates auditory brain areas to a greater degree than nonnative, whereas nonnative speech activates motor brain areas to a greater degree than native speech. This double dissociation in 11- to 12-mo-old infants matches the pattern of results obtained in adult listeners. Our infant data are consistent with Analysis by Synthesis: auditory analysis of speech is coupled with synthesis of the motor plans necessary to produce the speech signal. The findings have implications for: (i) perception-action theories of speech perception, (ii) the impact of "motherese" on early language learning, and (iii) the "social-gating" hypothesis and humans' development of social understanding.

Early parental care is important for hippocampal maturation: evidence from brain morphology in humans.

PubMed

Rao, Hengyi; Betancourt, Laura; Giannetta, Joan M; Brodsky, Nancy L; Korczykowski, Marc; Avants, Brian B; Gee, James C; Wang, Jiongjiong; Hurt, Hallam; Detre, John A; Farah, Martha J

2010-01-01

The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation.

Early brain development in infants at high risk for autism spectrum disorder

PubMed Central

Hazlett, Heather Cody; Gu, Hongbin; Munsell, Brent C.; Kim, Sun Hyung; Styner, Martin; Wolff, Jason J.; Elison, Jed T.; Swanson, Meghan R.; Zhu, Hongtu; Botteron, Kelly N.; Collins, D. Louis; Constantino, John N.; Dager, Stephen R.; Estes, Annette M.; Evans, Alan C.; Fonov, Vladimir S.; Gerig, Guido; Kostopoulos, Penelope; McKinstry, Robert C.; Pandey, Juhi; Paterson, Sarah; Pruett, John R.; Schultz, Robert T.; Shaw, Dennis W.; Zwaigenbaum, Lonnie; Piven, Joseph

2017-01-01

Summary Brain enlargement has been observed in children with Autism Spectrum Disorder (ASD), but the timing of this phenomenon and its relationship to the appearance of behavioral symptoms is unknown. Retrospective head circumference and longitudinal brain volume studies of 2 year olds followed up at age 4 years, have provided evidence that increased brain volume may emerge early in development.1, 2 Studies of infants at high familial risk for autism can provide insight into the early development of autism and have found that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life3,4. These observations suggest that prospective brain imaging studies of infants at high familial risk for ASD might identify early post-natal changes in brain volume occurring before the emergence of an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that cortical surface area hyper-expansion between 6-12 months of age precedes brain volume overgrowth observed between 12-24 months in the 15 high-risk infants diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep learning algorithm primarily using surface area information from brain MRI at 6 and 12 months of age predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81%, sensitivity of 88%). These findings demonstrate that early brain changes unfold during the period in which autistic behaviors are first emerging. PMID:28202961

Early brain development in infants at high risk for autism spectrum disorder.

PubMed

Hazlett, Heather Cody; Gu, Hongbin; Munsell, Brent C; Kim, Sun Hyung; Styner, Martin; Wolff, Jason J; Elison, Jed T; Swanson, Meghan R; Zhu, Hongtu; Botteron, Kelly N; Collins, D Louis; Constantino, John N; Dager, Stephen R; Estes, Annette M; Evans, Alan C; Fonov, Vladimir S; Gerig, Guido; Kostopoulos, Penelope; McKinstry, Robert C; Pandey, Juhi; Paterson, Sarah; Pruett, John R; Schultz, Robert T; Shaw, Dennis W; Zwaigenbaum, Lonnie; Piven, Joseph

2017-02-15

Brain enlargement has been observed in children with autism spectrum disorder (ASD), but the timing of this phenomenon, and the relationship between ASD and the appearance of behavioural symptoms, are unknown. Retrospective head circumference and longitudinal brain volume studies of two-year olds followed up at four years of age have provided evidence that increased brain volume may emerge early in development. Studies of infants at high familial risk of autism can provide insight into the early development of autism and have shown that characteristic social deficits in ASD emerge during the latter part of the first and in the second year of life. These observations suggest that prospective brain-imaging studies of infants at high familial risk of ASD might identify early postnatal changes in brain volume that occur before an ASD diagnosis. In this prospective neuroimaging study of 106 infants at high familial risk of ASD and 42 low-risk infants, we show that hyperexpansion of the cortical surface area between 6 and 12 months of age precedes brain volume overgrowth observed between 12 and 24 months in 15 high-risk infants who were diagnosed with autism at 24 months. Brain volume overgrowth was linked to the emergence and severity of autistic social deficits. A deep-learning algorithm that primarily uses surface area information from magnetic resonance imaging of the brain of 6-12-month-old individuals predicted the diagnosis of autism in individual high-risk children at 24 months (with a positive predictive value of 81% and a sensitivity of 88%). These findings demonstrate that early brain changes occur during the period in which autistic behaviours are first emerging.

Brain Development and Early Learning: Research on Brain Development. Quality Matters. Volume 1, Winter 2007

ERIC Educational Resources Information Center

Edie, David; Schmid, Deborah

2007-01-01

For decades researchers have been aware of the extraordinary development of a child's brain during the first five years of life. Recent advances in neuroscience have helped crystallize earlier findings, bringing new clarity and understanding to the field of early childhood brain development. Children are born ready to learn. They cultivate 85…

Joint Pairing and Structured Mapping of Convolutional Brain Morphological Multiplexes for Early Dementia Diagnosis.

PubMed

Lisowska, Anna; Rekik, Islem

2018-06-21

Diagnosis of brain dementia, particularly early mild cognitive impairment (eMCI), is critical for early intervention to prevent the onset of Alzheimer's Disease (AD), where cognitive decline is severe and irreversible. There is a large body of machine-learning based research investigating how dementia alters brain connectivity, mainly using structural (derived from diffusion MRI) and functional (derived from resting-state functional MRI) brain connectomic data. However, how early dementia affects cortical brain connections in morphology remains largely unexplored. To fill this gap, we propose a joint morphological brain multiplexes pairing and mapping strategy for early MCI detection, where a brain multiplex not only encodes the similarity in morphology between pairs of brain regions, but also a pair of brain morphological networks. Experimental results confirm that the proposed framework outperforms in classification accuracy several state-of-the-art methods. More importantly, we unprecedentedly identified most discriminative brain morphological networks between eMCI and NC, which included the paired views derived from maximum principal curvature and the sulcal depth for the left hemisphere and sulcal depth and the average curvature for the right hemisphere. We also identified the most highly correlated morphological brain connections in our cohort, which included the (pericalcarine cortex, insula cortex) on the maximum principal curvature view, (entorhinal cortex, insula cortex) on the mean sulcal depth view, and (entorhinal cortex, pericalcarine cortex) on the mean average curvature view, for both hemispheres. These highly correlated morphological connections might serve as biomarkers for early MCI diagnosis.

Infants’ brain responses to speech suggest Analysis by Synthesis

PubMed Central

Kuhl, Patricia K.; Ramírez, Rey R.; Bosseler, Alexis; Lin, Jo-Fu Lotus; Imada, Toshiaki

2014-01-01

Historic theories of speech perception (Motor Theory and Analysis by Synthesis) invoked listeners’ knowledge of speech production to explain speech perception. Neuroimaging data show that adult listeners activate motor brain areas during speech perception. In two experiments using magnetoencephalography (MEG), we investigated motor brain activation, as well as auditory brain activation, during discrimination of native and nonnative syllables in infants at two ages that straddle the developmental transition from language-universal to language-specific speech perception. Adults are also tested in Exp. 1. MEG data revealed that 7-mo-old infants activate auditory (superior temporal) as well as motor brain areas (Broca’s area, cerebellum) in response to speech, and equivalently for native and nonnative syllables. However, in 11- and 12-mo-old infants, native speech activates auditory brain areas to a greater degree than nonnative, whereas nonnative speech activates motor brain areas to a greater degree than native speech. This double dissociation in 11- to 12-mo-old infants matches the pattern of results obtained in adult listeners. Our infant data are consistent with Analysis by Synthesis: auditory analysis of speech is coupled with synthesis of the motor plans necessary to produce the speech signal. The findings have implications for: (i) perception-action theories of speech perception, (ii) the impact of “motherese” on early language learning, and (iii) the “social-gating” hypothesis and humans’ development of social understanding. PMID:25024207

Prenatal cocaine effects on brain structure in early infancy.

PubMed

Grewen, Karen; Burchinal, Margaret; Vachet, Clement; Gouttard, Sylvain; Gilmore, John H; Lin, Weili; Johns, Josephine; Elam, Mala; Gerig, Guido

2014-11-01

Prenatal cocaine exposure (PCE) is related to subtle deficits in cognitive and behavioral function in infancy, childhood and adolescence. Very little is known about the effects of in utero PCE on early brain development that may contribute to these impairments. The purpose of this study was to examine brain structural differences in infants with and without PCE. We conducted MRI scans of newborns (mean age = 5 weeks) to determine cocaine's impact on early brain structural development. Subjects were three groups of infants: 33 with PCE co-morbid with other drugs, 46 drug-free controls and 40 with prenatal exposure to other drugs (nicotine, alcohol, marijuana, opiates, SSRIs) but without cocaine. Infants with PCE exhibited lesser total gray matter (GM) volume and greater total cerebral spinal fluid (CSF) volume compared with controls and infants with non-cocaine drug exposure. Analysis of regional volumes revealed that whole brain GM differences were driven primarily by lesser GM in prefrontal and frontal brain regions in infants with PCE, while more posterior regions (parietal, occipital) did not differ across groups. Greater CSF volumes in PCE infants were present in prefrontal, frontal and parietal but not occipital regions. Greatest differences (GM reduction, CSF enlargement) in PCE infants were observed in dorsal prefrontal cortex. Results suggest that PCE is associated with structural deficits in neonatal cortical gray matter, specifically in prefrontal and frontal regions involved in executive function and inhibitory control. Longitudinal study is required to determine whether these early differences persist and contribute to deficits in cognitive functions and enhanced risk for drug abuse seen at school age and in later life. Copyright © 2014 Elsevier Inc. All rights reserved.

Brain signatures of early lexical and morphological learning of a new language.

PubMed

Havas, Viktória; Laine, Matti; Rodríguez Fornells, Antoni

2017-07-01

Morphology is an important part of language processing but little is known about how adult second language learners acquire morphological rules. Using a word-picture associative learning task, we have previously shown that a brief exposure to novel words with embedded morphological structure (suffix for natural gender) is enough for language learners to acquire the hidden morphological rule. Here we used this paradigm to study the brain signatures of early morphological learning in a novel language in adults. Behavioural measures indicated successful lexical (word stem) and morphological (gender suffix) learning. A day after the learning phase, event-related brain potentials registered during a recognition memory task revealed enhanced N400 and P600 components for stem and suffix violations, respectively. An additional effect observed with combined suffix and stem violations was an enhancement of an early N2 component, most probably related to conflict-detection processes. Successful morphological learning was also evident in the ERP responses to the subsequent rule-generalization task with new stems, where violation of the morphological rule was associated with an early (250-400ms) and late positivity (750-900ms). Overall, these findings tend to converge with lexical and morphosyntactic violation effects observed in L1 processing, suggesting that even after a short exposure, adult language learners can acquire both novel words and novel morphological rules. Copyright © 2017 Elsevier Ltd. All rights reserved.

How Early Events Affect Growing Brains. An Interview with Neuroscientist Pat Levitt

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2006

2006-01-01

Recent advances in neuroscience show clearly how experience can change brain neurochemicals, and how this in turn affects the way the brain functions. As a result, early negative events actually get built into the growing brain's neurochemistry, altering the brain's architecture. Research is continuing to investigate how children with genetic…

Early Brain Development Research Review and Update

ERIC Educational Resources Information Center

Schiller, Pam

2010-01-01

Thanks to imaging technology used in neurobiology, people have access to useful and critical information regarding the development of the human brain. This information allows them to become much more effective in helping children in their early development. In fact, when people base their practices on the findings from medical science research,…

How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture

PubMed Central

Fox, Sharon E.; Levitt, Pat; Nelson, Charles A.

2009-01-01

Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this paper a conceptual framework is provided for considering how the structure of early experience gets “under the skin.” The paper begins with a description of the genetic framework that lays the foundation for brain development, and then to the ways experience interacts with and modifies the structures and functions of the developing brain. Much of the attention is focused on early experience and sensitive periods, although it is made clear that later experience also plays an important role in maintaining and elaborating this early wiring diagram, which is critical to establishing a solid footing for development beyond the early years. PMID:20331653

Voxel-based analysis of the immediate early gene, c-jun, in the honey bee brain after a sucrose stimulus.

PubMed

McNeill, M S; Robinson, G E

2015-06-01

Immediate early genes (IEGs) have served as useful markers of brain neuronal activity in mammals, and more recently in insects. The mammalian canonical IEG, c-jun, is part of regulatory pathways conserved in insects and has been shown to be responsive to alarm pheromone in honey bees. We tested whether c-jun was responsive in honey bees to another behaviourally relevant stimulus, sucrose, in order to further identify the brain regions involved in sucrose processing. To identify responsive regions, we developed a new method of voxel-based analysis of c-jun mRNA expression. We found that c-jun is expressed in somata throughout the brain. It was rapidly induced in response to sucrose stimuli, and it responded in somata near the antennal and mechanosensory motor centre, mushroom body calices and lateral protocerebrum, which are known to be involved in sucrose processing. c-jun also responded to sucrose in somata near the lateral suboesophageal ganglion, dorsal optic lobe, ventral optic lobe and dorsal posterior protocerebrum, which had not been previously identified by other methods. These results demonstrate the utility of voxel-based analysis of mRNA expression in the insect brain. © 2015 The Royal Entomological Society.

Changes of brain response induced by simulated weightlessness

NASA Astrophysics Data System (ADS)

Wei, Jinhe; Yan, Gongdong; Guan, Zhiqiang

The characteristics change of brain response was studied during 15° head-down tilt (HDT) comparing with 45° head-up tilt (HUT). The brain responses evaluated included the EEG power spectra change at rest and during mental arithmetic, and the event-related potentials (ERPs) of somatosensory, selective attention and mental arithmetic activities. The prominent feature of brain response change during HDT revealed that the brain function was inhibited to some extent. Such inhibition included that the significant increment of "40Hz" activity during HUT arithmetic almost disappeared during HDT arithmetic, and that the positive-potential effect induced by HDT presented in all kinds of ERPs measured, but the slow negative wave reflecting mental arithmetic and memory process was elongated. These data suggest that the brain function be affected profoundly by the simulated weightlessness, therefore, the brain function change during space flight should be studied systematically.

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.

PubMed

Chen, Yuncai; Baram, Tallie Z

2016-01-01

Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes 'normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational

Brain Ischemia Induces Diversified Neuroantigen-Specific T-Cell Responses That Exacerbate Brain Injury.

PubMed

Jin, Wei-Na; Gonzales, Rayna; Feng, Yan; Wood, Kristofer; Chai, Zhi; Dong, Jing-Fei; La Cava, Antonio; Shi, Fu-Dong; Liu, Qiang

2018-06-01

Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury. Using a mouse strain that harbors a transgenic T-cell receptor to a central nervous system antigen, MOG 35-55 (myelin oligodendrocyte glycoprotein) epitope (2D2), we determined the anatomic location and involvement of antigen-presenting cells in the development of T-cell reactivity after brain ischemia and how T-cell reactivity impacts stroke outcome. Transient middle cerebral artery occlusion and photothrombotic stroke models were used in this study. We also quantified the presence and status of T cells from brain slices of ischemic patients. By coupling transfer of labeled MOG 35-55 -specific (2D2) T cells with tetramer tracking, we show an expansion in reactivity of 2D2 T cells to MOG 91-108 and MOG 103-125 in transient middle cerebral artery occlusion and photothrombotic stroke models. This reactivity and T-cell activation first occur locally in the brain after ischemia. Also, microglia act as antigen-presenting cells that effectively present MOG antigens, and depletion of microglia ablates expansion of 2D2 reactive T cells. Notably, the adoptive transfer of neuroantigen-experienced 2D2 T cells exacerbates Th1/Th17 responses and brain injury. Finally, T-cell activation and MOG-specific T cells are present in the brain of patients with ischemic stroke. Our findings suggest that brain ischemia activates and diversifies T-cell responses locally, which exacerbates ischemic brain injury. © 2018 The Authors.

Mind Over Matter: The Brain's Response to Marijuana

MedlinePlus

... Brain's Response to Marijuana The Brain's Response to Marijuana Print Hi, my name is Sara Bellum. Welcome ... issue, we'll investigate the fascinating facts about marijuana. You may have heard it called pot, weed, ...

Early Brain and Child Development: Connections to Early Education and Child Care

ERIC Educational Resources Information Center

Romano, Judith T.

2013-01-01

The vast majority of young children spend time in settings outside of the home, and the nature of those settings directly impacts the child's health and development. The ecobiodevelopmental framework of early brain and child development serve as the backdrop for establishing quality. This article describes the use of quality rating systems,…

Genomic responses in rat cerebral cortex after traumatic brain injury

PubMed Central

von Gertten, Christina; Morales, Amilcar Flores; Holmin, Staffan; Mathiesen, Tiit; Nordqvist, Ann-Christin Sandberg

2005-01-01

Background Traumatic brain injury (TBI) initiates a complex sequence of destructive and neuroprotective cellular responses. The initial mechanical injury is followed by an extended time period of secondary brain damage. Due to the complicated pathological picture a better understanding of the molecular events occurring during this secondary phase of injury is needed. This study was aimed at analysing gene expression patterns following cerebral cortical contusion in rat using high throughput microarray technology with the goal of identifying genes involved in an early and in a more delayed phase of trauma, as genomic responses behind secondary mechanisms likely are time-dependent. Results Among the upregulated genes 1 day post injury, were transcription factors and genes involved in metabolism, e.g. STAT-3, C/EBP-δ and cytochrome p450. At 4 days post injury we observed increased gene expression of inflammatory factors, proteases and their inhibitors, like cathepsins, α-2-macroglobulin and C1q. Notably, genes with biological function clustered to immune response were significantly upregulated 4 days after injury, which was not found following 1 day. Osteopontin and one of its receptors, CD-44, were both upregulated showing a local mRNA- and immunoreactivity pattern in and around the injury site. Fewer genes had decreased expression both 1 and 4 days post injury and included genes implicated in transport, metabolism, signalling, and extra cellular matrix formation, e.g. vitronectin, neuroserpin and angiotensinogen. Conclusion The different patterns of gene expression, with little overlap in genes, 1 and 4 days post injury showed time dependence in genomic responses to trauma. An early induction of factors involved in transcription could lead to the later inflammatory response with strongly upregulated CD-44 and osteopontin expression. An increased knowledge of genes regulating the pathological mechanisms in trauma will help to find future treatment targets. Since

Pedophilic brain potential responses to adult erotic stimuli.

PubMed

Knott, Verner; Impey, Danielle; Fisher, Derek; Delpero, Emily; Fedoroff, Paul

2016-02-01

Cognitive mechanisms associated with the relative lack of sexual interest in adults by pedophiles are poorly understood and may benefit from investigations examining how the brain processes adult erotic stimuli. The current study used event-related brain potentials (ERP) to investigate the time course of the explicit processing of erotic, emotional, and neutral pictures in 22 pedophilic patients and 22 healthy controls. Consistent with previous studies, early latency anterior ERP components were highly selective for erotic pictures. Although the ERPs elicited by emotional stimuli were similar in patients and controls, an early frontal positive (P2) component starting as early as 185 ms was significantly attenuated and slow to onset in pedophilia, and correlated with a clinical measure of cognitive distortions. Failure of rapid attentional capture by erotic stimuli suggests a relative reduction in early processing in pedophilic patients which may be associated with relatively diminished sexual interest in adults. Copyright © 2016. Published by Elsevier B.V.

Restrained eaters show altered brain response to food odor.

PubMed

Kemmotsu, Nobuko; Murphy, Claire

2006-02-28

Do restrained and unrestrained eaters differ in their brain response to food odor? We addressed this question by examining restrained eaters' brain response to food (chocolate) and non-food (geraniol, floral) odors, both when odor was attended to and when ignored. Using olfactory event-related potentials (OERPs), we found that restrained eaters and controls responded similarly to the non-food odor; however, unlike controls, restrained eaters showed no increase in brain response to the food odor when they focused attention on it. Rather, restrained eaters showed attenuated OERP amplitudes to the food odor in both attended and ignored conditions, suggesting that the brain's response to attended food odor was abnormally suppressed.

Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

PubMed

Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

2009-01-01

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

Brain responses in 4-month-old infants are already language specific.

PubMed

Friederici, Angela D; Friedrich, Manuela; Christophe, Anne

2007-07-17

Language is the most important faculty that distinguishes humans from other animals. Infants learn their native language fast and effortlessly during the first years of life, as a function of the linguistic input in their environment. Behavioral studies reported the discrimination of melodic contours [1] and stress patterns [2, 3] in 1-4-month-olds. Behavioral [4, 5] and brain measures [6-8] have shown language-independent discrimination of phonetic contrasts at that age. Language-specific discrimination, however, has been reported for phonetic contrasts only for 6-12-month-olds [9-12]. Here we demonstrate language-specific discrimination of stress patterns in 4-month-old German and French infants by using electrophysiological brain measures. We compare the processing of disyllabic words differing in their rhythmic structure, mimicking German words being stressed on the first syllable, e.g., pápa/daddy[13], and French ones being stressed on the second syllable, e.g., papá/daddy. Event-related brain potentials reveal that experience with German and French differentially affects the brain responses of 4-month-old infants, with each language group displaying a processing advantage for the rhythmic structure typical in its native language. These data indicate language-specific neural representations of word forms in the infant brain as early as 4 months of age.

Early Adverse Caregiving Experiences and Preschoolers' Current Attachment Affect Brain Responses during Facial Familiarity Processing: An ERP Study.

PubMed

Kungl, Melanie T; Bovenschen, Ina; Spangler, Gottfried

2017-01-01

When being placed into more benign environments like foster care, children from adverse rearing backgrounds are capable of forming attachment relationships to new caregivers within the first year of placement, while certain problematic social behaviors appear to be more persistent. Assuming that early averse experiences shape neural circuits underlying social behavior, neurophysiological studies on individual differences in early social-information processing have great informative value. More precisely, ERP studies have repeatedly shown face processing to be sensitive to experience especially regarding the caregiving background. However, studies on effects of early adverse caregiving experiences are restricted to children with a history of institutionalization. Also, no study has investigated effects of attachment security as a marker of the quality of the caregiver-child relationship. Thus, the current study asks how adverse caregiving experiences and attachment security to (new) caregivers affect early- and mid-latency ERPs sensitive to facial familiarity processing. Therefore, pre-school aged foster children during their second year within the foster home were compared to an age matched control group. Attachment was assessed using the AQS and neurophysiological data was collected during a passive viewing task presenting (foster) mother and stranger faces. Foster children were comparable to the control group with regard to attachment security. On a neurophysiological level, however, the foster group showed dampened N170 amplitudes for both face types. In both foster and control children, dampened N170 amplitudes were also found for stranger as compared to (foster) mother faces, and, for insecurely attached children as compared to securely attached children. This neural pattern may be viewed as a result of poorer social interactions earlier in life. Still, there was no effect on P1 amplitudes. Indicating heightened attentional processing, Nc amplitude responses

Regional brain activity during early-stage intense romantic love predicted relationship outcomes after 40 months: an fMRI assessment.

PubMed

Xu, Xiaomeng; Brown, Lucy; Aron, Arthur; Cao, Guikang; Feng, Tingyong; Acevedo, Bianca; Weng, Xuchu

2012-09-20

Early-stage romantic love is associated with activation in reward and motivation systems of the brain. Can these localized activations, or others, predict long-term relationship stability? We contacted participants from a previous fMRI study of early-stage love by Xu et al. [34] after 40 months from initial assessments. We compared brain activation during the initial assessment at early-stage love for those who were still together at 40 months and those who were apart, and surveyed those still together about their relationship happiness and commitment at 40 months. Six participants who were still with their partners at 40 months (compared to six who had broken up) showed less activation during early-stage love in the medial orbitofrontal cortex, right subcallosal cingulate and right accumbens, regions implicated in long-term love and relationship satisfaction [1,2]. These regions of deactivation at the early stage of love were also negatively correlated with relationship happiness scores collected at 40 months. Other areas involved were the caudate tail, and temporal and parietal lobes. These data are preliminary evidence that neural responses in the early stages of romantic love can predict relationship stability and quality up to 40 months later in the relationship. The brain regions involved suggest that forebrain reward functions may be predictive for relationship stability, as well as regions involved in social evaluation, emotional regulation, and mood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Study of a fetal brain affected by a severe form of tyrosine hydroxylase deficiency, a rare cause of early parkinsonism.

PubMed

Tristán-Noguero, Alba; Díez, Héctor; Jou, Cristina; Pineda, Mercè; Ormazábal, Aida; Sánchez, Aurora; Artuch, Rafael; Garcia-Cazorla, Àngels

2016-06-01

Tyrosine hydroxylase (TH) deficiency is an inborn error of dopamine synthesis. Two clinical phenotypes have been described. The THD "B" phenotype produces a severe encephalopathy of early-onset with sub-optimal L-Dopa response, whereas the "A" phenotype has a better L-Dopa response and outcome. The objective of the study is to describe the expression of key synaptic proteins and neurodevelopmental markers in a fetal brain of THD "B" phenotype. The brain of a 16-week-old miscarried human fetus was dissected in different brain areas and frozen until the analysis. TH gene study revealed the p.R328W/p.T399M mutations, the same mutations that produced a B phenotype in her sister. After protein extraction, western blot analyses were performed to assess protein expression. The results were compared to an age-matched control. We observed a decreased expression in TH and in other dopaminergic proteins, such as VMAT 1 and 2 and dopamine receptors, especially D2DR. GABAergic and glutamatergic proteins such as GABA VT, NMDAR1 and calbindin were also altered. Developmental markers for synapses, axons and dendrites were decreased whereas markers of neuronal volume were preserved. Although this is an isolated case, this brain sample is unique and corresponds to the first reported study of a THD brain. It provides interesting information about the influence of dopamine as a regulator of other neurotransmitter systems, brain development and movement disorders with origin at the embryological state. This study could also contribute to a better understanding of the pathophysiology of THD at early fetal stages.

Children processing music: electric brain responses reveal musical competence and gender differences.

PubMed

Koelsch, Stefan; Grossmann, Tobias; Gunter, Thomas C; Hahne, Anja; Schröger, Erich; Friederici, Angela D

2003-07-01

Numerous studies investigated physiological correlates of the processing of musical information in adults. How these correlates develop during childhood is poorly understood. In the present study, we measured event-related electric brain potentials elicited in 5- and 9-year-old children while they listened to (major-minor tonal) music. Stimuli were chord sequences, infrequently containing harmonically inappropriate chords. Our results demonstrate that the degree of (in)appropriateness of the chords modified the brain responses in both groups according to music-theoretical principles. This suggests that already 5-year-old children process music according to a well-established cognitive representation of the major-minor tonal system and according to music-syntactic regularities. Moreover, we show that, in contrast to adults, an early negative brain response was left predominant in boys, whereas it was bilateral in girls, indicating a gender difference in children processing music, and revealing that children process music with a hemispheric weighting different from that of adults. Because children process, in contrast to adults, music in the same hemispheres as they process language, results indicate that children process music and language more similarly than adults. This finding might support the notion of a common origin of music and language in the human brain, and concurs with findings that demonstrate the importance of musical features of speech for the acquisition of language.

Real-time photoacoustic imaging of rat deep brain: hemodynamic responses to hypoxia

NASA Astrophysics Data System (ADS)

Kawauchi, Satoko; Iwazaki, Hideaki; Ida, Taiichiro; Hosaka, Tomoya; Kawaguchi, Yasushi; Nawashiro, Hiroshi; Sato, Shunichi

2013-03-01

Hemodynamic responses of the brain to hypoxia or ischemia are one of the major interests in neurosurgery and neuroscience. In this study, we performed real-time transcutaneous PA imaging of the rat brain that was exposed to a hypoxic stress and investigated depth-resolved responses of the brain, including the hippocampus. A linear-array 8ch 10-MHz ultrasonic sensor (measurement length, 10 mm) was placed on the shaved scalp. Nanosecond, 570-nm and 595- nm light pulses were used to excite PA signals indicating cerebral blood volume (CBV) and blood deoxygenation, respectively. Under spontaneous respiration, inhalation gas was switched from air to nitrogen, and then reswitched to oxygen, during which real-time PA imaging was performed continuously. High-contrast PA signals were observed from the depth regions corresponding to the scalp, skull, cortex and hippocampus. After starting hypoxia, PA signals at 595 nm increased immediately in both the cortex and hippocampus for about 1.5 min, showing hemoglobin deoxygenation. On the other hand, PA signals at 570 nm coming from these regions did not increase in the early phase but started to increase at about 1.5 min after starting hypoxia, indicating reactive hyperemia to hypoxia. During hypoxia, PA signals coming from the scalp decreased transiently, which is presumably due to compensatory response in the peripheral tissue to preserve blood perfusion in the brain. The reoxygenation caused a gradual recovery of these PA signals. These findings demonstrate the usefulness of PA imaging for real-time, depth-resolved observation of cerebral hemodynamics.

fMRI during natural sleep as a method to study brain function during early childhood.

PubMed

Redcay, Elizabeth; Kennedy, Daniel P; Courchesne, Eric

2007-12-01

Many techniques to study early functional brain development lack the whole-brain spatial resolution that is available with fMRI. We utilized a relatively novel method in which fMRI data were collected from children during natural sleep. Stimulus-evoked responses to auditory and visual stimuli as well as stimulus-independent functional networks were examined in typically developing 2-4-year-old children. Reliable fMRI data were collected from 13 children during presentation of auditory stimuli (tones, vocal sounds, and nonvocal sounds) in a block design. Twelve children were presented with visual flashing lights at 2.5 Hz. When analyses combined all three types of auditory stimulus conditions as compared to rest, activation included bilateral superior temporal gyri/sulci (STG/S) and right cerebellum. Direct comparisons between conditions revealed significantly greater responses to nonvocal sounds and tones than to vocal sounds in a number of brain regions including superior temporal gyrus/sulcus, medial frontal cortex and right lateral cerebellum. The response to visual stimuli was localized to occipital cortex. Furthermore, stimulus-independent functional connectivity MRI analyses (fcMRI) revealed functional connectivity between STG and other temporal regions (including contralateral STG) and medial and lateral prefrontal regions. Functional connectivity with an occipital seed was localized to occipital and parietal cortex. In sum, 2-4 year olds showed a differential fMRI response both between stimulus modalities and between stimuli in the auditory modality. Furthermore, superior temporal regions showed functional connectivity with numerous higher-order regions during sleep. We conclude that the use of sleep fMRI may be a valuable tool for examining functional brain organization in young children.

Enhanced microglial pro-inflammatory response to lipopolysaccharide correlates with brain infiltration and blood-brain barrier dysregulation in a mouse model of telomere shortening.

PubMed

Raj, Divya D A; Moser, Jill; van der Pol, Susanne M A; van Os, Ronald P; Holtman, Inge R; Brouwer, Nieske; Oeseburg, Hisko; Schaafsma, Wandert; Wesseling, Evelyn M; den Dunnen, Wilfred; Biber, Knut P H; de Vries, Helga E; Eggen, Bart J L; Boddeke, Hendrikus W G M

2015-12-01

Microglia are a proliferative population of resident brain macrophages that under physiological conditions self-renew independent of hematopoiesis. Microglia are innate immune cells actively surveying the brain and are the earliest responders to injury. During aging, microglia elicit an enhanced innate immune response also referred to as 'priming'. To date, it remains unknown whether telomere shortening affects the proliferative capacity and induces priming of microglia. We addressed this issue using early (first-generation G1 mTerc(-/-) )- and late-generation (third-generation G3 and G4 mTerc(-/-) ) telomerase-deficient mice, which carry a homozygous deletion for the telomerase RNA component gene (mTerc). Late-generation mTerc(-/-) microglia show telomere shortening and decreased proliferation efficiency. Under physiological conditions, gene expression and functionality of G3 mTerc(-/-) microglia are comparable with microglia derived from G1 mTerc(-/-) mice despite changes in morphology. However, after intraperitoneal injection of bacterial lipopolysaccharide (LPS), G3 mTerc(-/-) microglia mice show an enhanced pro-inflammatory response. Nevertheless, this enhanced inflammatory response was not accompanied by an increased expression of genes known to be associated with age-associated microglia priming. The increased inflammatory response in microglia correlates closely with increased peripheral inflammation, a loss of blood-brain barrier integrity, and infiltration of immune cells in the brain parenchyma in this mouse model of telomere shortening. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Heme oxygenase-1 exacerbates early brain injury after intracerebral haemorrhage

PubMed Central

Wang, Jian; Doré, Sylvain

2008-01-01

Because heme oxygenase (HO) is the rate limiting enzyme in the degradation of the pro-oxidant hemin/heme from blood, here we investigated the contribution of the inducible HO-1 to early brain injury produced by intracerebral haemorrhage (ICH). We found that after induction of ICH, HO-1 proteins were highly detectable in the peri-ICH region predominantly in microglia/macrophages and endothelial cells. Remarkably, the injury volume was significantly smaller in HO-1 knockout (HO-1−/−) mice than in wild-type controls 24 and 72 h after ICH. Although the brain water content did not appear to be significantly different, the protection in HO-1−/− mice was associated with a marked reduction in ICH-induced leucocyte infiltration, microglia/macrophage activation and free radical levels. These data reveal a previously unrecognized role of HO-1 in early brain injury after ICH. Thus, modulation of HO-1 signalling should be assessed further in clinical settings, especially for haemorrhagic states. PMID:17525142

Research Review: Cholinergic Mechanisms, Early Brain Development, and Risk for Schizophrenia

ERIC Educational Resources Information Center

Ross, Randal G.; Stevens, Karen E.; Proctor, William R.; Leonard, Sherry; Kisley, Michael A.; Hunter, Sharon K.; Freedman, Robert; Adams, Catherine E.

2010-01-01

The onset of diagnostic symptomology for neuropsychiatric diseases is often the end result of a decades-long process of aberrant brain development. Identification of novel treatment strategies aimed at normalizing early brain development and preventing mental illness should be a major therapeutic goal. However, there are few models for how this…

A Survey of English Sixth Formers' Knowledge of Early Brain Development.

PubMed

Nolan, Mary

2017-10-01

Objectives To ascertain the knowledge of young people aged 16 to 19 of early brain development and their attitudes towards the care of babies and preschool children. Design Cross-sectional, school- and college-based survey including all sixth form students present on the days of data collection. The survey instrument comprised forced-choice questions in four sections: Demographics, Perceptions and Understanding of Early Childhood Development, Parental Behaviors to Support Early Brain development, and Resource Needs and Usage. Setting Two sixth form schools and one sixth form college in three towns of varying affluence in the West Midlands of the United Kingdom. Method The survey was mounted online and completed by 905 students who returned it directly to the researcher. Results Most students knew that tobacco, alcohol, and drugs are hazardous in pregnancy, and many recognized the impact of maternal stress on fetal brain development. Many believed that babies can be "spoiled" and did not appreciate the importance of reading to babies and of the relationship between play and early brain development. A significant minority thought that physical activity and a healthy diet have little impact on young children's development. Respondents said they would turn firstly to their parents for advice on baby care rather than professionals. Conclusion Young people need educating about parenting activities that support the all-round healthy development of infants. The importance of a healthy diet, physical activity, reading, and play should be included in sixth form curricula and antenatal classes. Consideration should be given to educating grandparents because of their influence on new parents.

Global Genetic Variations Predict Brain Response to Faces

PubMed Central

Dickie, Erin W.; Tahmasebi, Amir; French, Leon; Kovacevic, Natasa; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun; Büchel, Christian; Conrod, Patricia; Flor, Herta; Garavan, Hugh; Gallinat, Juergen; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Lawrence, Claire; Mann, Karl; Martinot, Jean-Luc; Nees, Frauke; Nichols, Thomas; Lathrop, Mark; Loth, Eva; Pausova, Zdenka; Rietschel, Marcela; Smolka, Michal N.; Ströhle, Andreas; Toro, Roberto; Schumann, Gunter; Paus, Tomáš

2014-01-01

Face expressions are a rich source of social signals. Here we estimated the proportion of phenotypic variance in the brain response to facial expressions explained by common genetic variance captured by ∼500,000 single nucleotide polymorphisms. Using genomic-relationship-matrix restricted maximum likelihood (GREML), we related this global genetic variance to that in the brain response to facial expressions, as assessed with functional magnetic resonance imaging (fMRI) in a community-based sample of adolescents (n = 1,620). Brain response to facial expressions was measured in 25 regions constituting a face network, as defined previously. In 9 out of these 25 regions, common genetic variance explained a significant proportion of phenotypic variance (40–50%) in their response to ambiguous facial expressions; this was not the case for angry facial expressions. Across the network, the strength of the genotype-phenotype relationship varied as a function of the inter-individual variability in the number of functional connections possessed by a given region (R2 = 0.38, p<0.001). Furthermore, this variability showed an inverted U relationship with both the number of observed connections (R2 = 0.48, p<0.001) and the magnitude of brain response (R2 = 0.32, p<0.001). Thus, a significant proportion of the brain response to facial expressions is predicted by common genetic variance in a subset of regions constituting the face network. These regions show the highest inter-individual variability in the number of connections with other network nodes, suggesting that the genetic model captures variations across the adolescent brains in co-opting these regions into the face network. PMID:25122193

The effects of brain serotonin deficiency on behavioural disinhibition and anxiety-like behaviour following mild early life stress.

PubMed

Sachs, Benjamin D; Rodriguiz, Ramona M; Siesser, William B; Kenan, Alexander; Royer, Elizabeth L; Jacobsen, Jacob P R; Wetsel, William C; Caron, Marc G

2013-10-01

Aberrant serotonin (5-HT) signalling and exposure to early life stress have both been suggested to play a role in anxiety- and impulsivity-related behaviours. However, whether congenital 5-HT deficiency × early life stress interactions influence the development of anxiety- or impulsivity-like behaviour has not been established. Here, we examined the effects of early life maternal separation (MS) stress on anxiety-like behaviour and behavioural disinhibition, a type of impulsivity-like behaviour, in wild-type (WT) and tryptophan hydroxylase 2 (Tph2) knock-in (Tph2KI) mice, which exhibit ~60-80% reductions in the levels of brain 5-HT due to a R439H mutation in Tph2. We also investigated the effects of 5-HT deficiency and early life stress on adult hippocampal neurogenesis, plasma corticosterone levels and several signal transduction pathways in the amygdala. We demonstrate that MS slightly increases anxiety-like behaviour in WT mice and induces behavioural disinhibition in Tph2KI animals. We also demonstrate that MS leads to a slight decrease in cell proliferation within the hippocampus and potentiates corticosterone responses to acute stress, but these effects are not affected by brain 5-HT deficiency. However, we show that 5-HT deficiency leads to significant alterations in SGK-1 and GSK3β signalling and NMDA receptor expression in the amygdala in response to MS. Together, these findings support a potential role for 5-HT-dependent signalling in the amygdala in regulating the long-term effects of early life stress on anxiety-like behaviour and behavioural disinhibition.

Brain responses differ to faces of mothers and fathers.

PubMed

Arsalidou, Marie; Barbeau, Emmanuel J; Bayless, Sarah J; Taylor, Margot J

2010-10-01

We encounter many faces each day but relatively few are personally familiar. Once faces are familiar, they evoke semantic and social information known about the person. Neuroimaging studies demonstrate differential brain activity to familiar and non-familiar faces; however, brain responses related to personally familiar faces have been more rarely studied. We examined brain activity with fMRI in adults in response to faces of their mothers and fathers compared to faces of celebrities and strangers. Overall, faces of mothers elicited more activity in core and extended brain regions associated with face processing, compared to fathers, celebrity or stranger faces. Fathers' faces elicited activity in the caudate, a deep brain structure associated with feelings of love. These new findings of differential brain responses elicited by faces of mothers and fathers are consistent with psychological research on attachment, evident even during adulthood. 2010 Elsevier Inc. All rights reserved.

Early Exposure to Toxic Substances Damages Brain Architecture. Working Paper #4

ERIC Educational Resources Information Center

National Scientific Council on the Developing Child, 2006

2006-01-01

New science shows that exposure to toxins prenatally or early in life can have a devastating and lifelong effect on the developing architecture of the brain. Exposures to many chemicals have much more severe consequences for embryos, fetuses, and young children, whose brains are still developing, than for adults. Substances that can have a truly…

External Validity of a Risk Stratification Score Predicting Early Distant Brain Failure and Salvage Whole Brain Radiation Therapy After Stereotactic Radiosurgery for Brain Metastases.

PubMed

Press, Robert H; Boselli, Danielle M; Symanowski, James T; Lankford, Scott P; McCammon, Robert J; Moeller, Benjamin J; Heinzerling, John H; Fasola, Carolina E; Burri, Stuart H; Patel, Kirtesh R; Asher, Anthony L; Sumrall, Ashley L; Curran, Walter J; Shu, Hui-Kuo G; Crocker, Ian R; Prabhu, Roshan S

2017-07-01

A scoring system using pretreatment factors was recently published for predicting the risk of early (≤6 months) distant brain failure (DBF) and salvage whole brain radiation therapy (WBRT) after stereotactic radiosurgery (SRS) alone. Four risk factors were identified: (1) lack of prior WBRT; (2) melanoma or breast histologic features; (3) multiple brain metastases; and (4) total volume of brain metastases <1.3 cm 3 , with each factor assigned 1 point. The purpose of this study was to assess the validity of this scoring system and its appropriateness for clinical use in an independent external patient population. We reviewed the records of 247 patients with 388 brain metastases treated with SRS between 2010 at 2013 at Levine Cancer Institute. The Press (Emory) risk score was calculated and applied to the validation cohort population, and subsequent risk groups were analyzed using cumulative incidence. The low-risk (LR) group had a significantly lower risk of early DBF than did the high-risk (HR) group (22.6% vs 44%, P=.004), but there was no difference between the HR and intermediate-risk (IR) groups (41.2% vs 44%, P=.79). Total lesion volume <1.3 cm 3  (P=.004), malignant melanoma (P=.007), and multiple metastases (P<.001) were validated as predictors for early DBF. Prior WBRT and breast cancer histologic features did not retain prognostic significance. Risk stratification for risk of early salvage WBRT were similar, with a trend toward an increased risk for HR compared with LR (P=.09) but no difference between IR and HR (P=.53). The 3-level Emory risk score was shown to not be externally valid, but the model was able to stratify between 2 levels (LR and not-LR [combined IR and HR]) for early (≤6 months) DBF. These results reinforce the importance of validating predictive models in independent cohorts. Further refinement of this scoring system with molecular information and in additional contemporary patient populations is warranted. Copyright © 2017

Early behavioral intervention, brain plasticity, and the prevention of autism spectrum disorder.

PubMed

Dawson, Geraldine

2008-01-01

Advances in the fields of cognitive and affective developmental neuroscience, developmental psychopathology, neurobiology, genetics, and applied behavior analysis have contributed to a more optimistic outcome for individuals with autism spectrum disorder (ASD). These advances have led to new methods for early detection and more effective treatments. For the first time, prevention of ASD is plausible. Prevention will entail detecting infants at risk before the full syndrome is present and implementing treatments designed to alter the course of early behavioral and brain development. This article describes a developmental model of risk, risk processes, symptom emergence, and adaptation in ASD that offers a framework for understanding early brain plasticity in ASD and its role in prevention of the disorder.

Responses of brain and non-brain endothelial cells to meningitis-causing Escherichia coli K1.

PubMed

Paul-Satyaseela, Maneesh; Xie, Yi; Di Cello, Francescopaolo; Kim, Kwang Sik

2006-03-31

Bacterial interaction with specific host tissue may contribute to its propensity to cause an infection in a particular site. In this study, we examined whether meningitis-causing Escherichia coli K1 interaction with human brain microvascular endothelial cells, which constitute the blood-brain barrier, differed from its interaction with non-brain endothelial cells derived from skin and umbilical cord. We showed that E. coli K1 association was significantly greater with human brain microvascular endothelial cells than with non-brain endothelial cells. In addition, human brain microvascular endothelial cells maintained their morphology and intercellular junctional resistance in response to E. coli K1. In contrast, non-brain endothelial cells exhibited decreased transendothelial electrical resistance and detachment from the matrix upon exposure to E. coli K1. These different responses of brain and non-brain endothelial cells to E. coli K1 may form the basis of E. coli K1's propensity to cause meningitis.

Early life stress-induced alterations in rat brain structures measured with high resolution MRI.

PubMed

Sarabdjitsingh, R Angela; Loi, Manila; Joëls, Marian; Dijkhuizen, Rick M; van der Toorn, Annette

2017-01-01

Adverse experiences early in life impair cognitive function both in rodents and humans. In humans this increases the vulnerability to develop mental illnesses while in the rodent brain early life stress (ELS) abnormalities are associated with changes in synaptic plasticity, excitability and microstructure. Detailed information on the effects of ELS on rodent brain structural integrity at large and connectivity within the brain is currently lacking; this information is highly relevant for understanding the mechanism by which early life stress predisposes to mental illnesses. Here, we exposed rats to 24 hours of maternal deprivation (MD) at postnatal day 3, a paradigm known to increase corticosterone levels and thereby activate glucocorticoid receptors in the brain. Using structural magnetic resonance imaging we examined: i) volumetric changes and white/grey matter properties of the whole cerebrum and of specific brain areas; and ii) whether potential alterations could be normalized by blocking glucocorticoid receptors with mifepristone during the critical developmental window of early adolescence, i.e. between postnatal days 26 and 28. The results show that MD caused a volumetric reduction of the prefrontal cortex, particularly the ventromedial part, and the orbitofrontal cortex. Within the whole cerebrum, white (relative to grey) matter volume was decreased and region-specifically in prefrontal cortex and dorsomedial striatum following MD. A trend was found for the hippocampus. Grey matter fractions were not affected. Treatment with mifepristone did not normalize these changes. This study indicates that early life stress in rodents has long lasting consequences for the volume and structural integrity of the brain. However, changes were relatively modest and-unlike behavior- not mitigated by blockade of glucocorticoid receptors during a critical developmental period.

Early brain development toward shaping of human mind: an integrative psychoneurodevelopmental model in prenatal and perinatal medicine.

PubMed

Hruby, Radovan; Maas, Lili M; Fedor-Freybergh, P G

2013-01-01

The article introduces an integrative psychoneurodevelopmental model of complex human brain and mind development based on the latest findings in prenatal and perinatal medicine in terms of integrative neuroscience. The human brain development is extraordinarily complex set of events and could be influenced by a lot of factors. It is supported by new insights into the early neuro-ontogenic processes with the help of structural 3D magnetic resonance imaging or diffusion tensor imaging of fetal human brain. Various factors and targets for neural development including birth weight variability, fetal and early-life programming, fetal neurobehavioral states and fetal behavioral responses to various stimuli and others are discussed. Molecular biology reveals increasing sets of genes families as well as transcription and neurotropic factors together with critical epigenetic mechanisms to be deeply employed in the crucial neurodevelopmental events. Another field of critical importance is psychoimmuno-neuroendocrinology. Various effects of glucocorticoids as well as other hormones, prenatal stress and fetal HPA axis modulation are thought to be of special importance for brain development. The early postnatal period is characterized by the next intense shaping of complex competences, induced mainly by the very unique mother - newborn´s interactions and bonding. All these mechanisms serve to shape individual human mind with complex abilities and neurobehavioral strategies. Continuous research elucidating these special competences of human fetus and newborn/child supports integrative neuroscientific approach to involve various scientific disciplines for the next progress in human brain and mind research, and opens new scientific challenges and philosophic attitudes. New findings and approaches in this field could establish new methods in science, in primary prevention and treatment strategies, and markedly contribute to the development of modern integrative and personalized

Cholinergic Mechanisms, Early Brain Development, and Risk for Schizophrenia

PubMed Central

Ross, Randal G; Stevens, Karen E; Proctor, William R; Leonard, Sherry; Kisley, Michael A; Hunter, Sharon K; Freedman, Robert; Adams, Catherine E

2009-01-01

Neuropsychiatric diseases are complex illnesses where the onset of diagnostic symptomology is often the end result of a decades-long process of aberrant brain development. The identification of novel treatment strategies aimed at normalizing early brain development and preventing mental illness should be a major therapeutic goal; however, there are few models for how this goal might be achieved. This report uses the attentional deficits of schizophrenia as an example and reviews data from genetic, anatomical, physiological, and pharmacologic studies to hypothesize a developmental model with translational primary prevention implications. Specifically, the model suggests that an early interaction between α7 nicotinic receptor density and choline availability may contribute to the development of schizophrenia-associated attentional deficits. Translational implications, including perinatal dietary choline supplementation, are discussed. It is hoped that presentation of this model will stimulate other efforts to develop empirically-driven primary prevention strategies. PMID:19925602

Early caregiving and physiological stress responses.

PubMed

Luecken, Linda J; Lemery, Kathryn S

2004-05-01

Inadequate early caregiving has been associated with risks of stress-related psychological and physical illness over the life span. Dysregulated physiological stress responses may represent a mechanism linking early caregiving to health outcomes. This paper reviews evidence linking early caregiving to physiological responses that can increase vulnerability to stress-related illness. A number of high-risk family characteristics, including high conflict, divorce, abuse, and parental psychopathology, are considered in the development of stress vulnerability. Three theoretical pathways linking caregiving to physiological stress responses are outlined: genetic, psychosocial, and cognitive-affective. Exciting preliminary evidence suggests that early caregiving can impact long-term physiological stress responses. Directions for future research in this area are suggested.

Optimization of SSVEP brain responses with application to eight-command Brain-Computer Interface.

PubMed

Bakardjian, Hovagim; Tanaka, Toshihisa; Cichocki, Andrzej

2010-01-18

This study pursues the optimization of the brain responses to small reversing patterns in a Steady-State Visual Evoked Potentials (SSVEP) paradigm, which could be used to maximize the efficiency of applications such as Brain-Computer Interfaces (BCI). We investigated the SSVEP frequency response for 32 frequencies (5-84 Hz), and the time dynamics of the brain response at 8, 14 and 28 Hz, to aid the definition of the optimal neurophysiological parameters and to outline the onset-delay and other limitations of SSVEP stimuli in applications such as our previously described four-command BCI system. Our results showed that the 5.6-15.3 Hz pattern reversal stimulation evoked the strongest responses, peaking at 12 Hz, and exhibiting weaker local maxima at 28 and 42 Hz. After stimulation onset, the long-term SSVEP response was highly non-stationary and the dynamics, including the first peak, was frequency-dependent. The evaluation of the performance of a frequency-optimized eight-command BCI system with dynamic neurofeedback showed a mean success rate of 98%, and a time delay of 3.4s. Robust BCI performance was achieved by all subjects even when using numerous small patterns clustered very close to each other and moving rapidly in 2D space. These results emphasize the need for SSVEP applications to optimize not only the analysis algorithms but also the stimuli in order to maximize the brain responses they rely on. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

The mating brain: early maturing sneaker males maintain investment into the brain also under fast body growth in Atlantic salmon (Salmo salar).

PubMed

Kotrschal, Alexander; Trombley, Susanne; Rogell, Björn; Brannström, Ioana; Foconi, Eric; Schmitz, Monika; Kolm, Niclas

It has been suggested that mating behaviours require high levels of cognitive ability. However, since investment into mating and the brain both are costly features, their relationship is likely characterized by energetic trade-offs. Empirical data on the subject remains equivocal. We investigated if early sexual maturation was associated with brain development in Atlantic salmon ( Salmo salar ), in which males can either stay in the river and sexually mature at a small size (sneaker males) or migrate to the sea and delay sexual maturation until they have grown much larger (anadromous males). Specifically, we tested how sexual maturation may induce plastic changes in brain development by rearing juveniles on either natural or ad libitum feeding levels. After their first season we compared brain size and brain region volumes across both types of male mating tactics and females. Body growth increased greatly across both male mating tactics and females during ad libitum feeding as compared to natural feeding levels. However, despite similar relative increases in body size, early maturing sneaker males maintained larger relative brain size during ad libitum feeding levels as compared to anadromous males and females. We also detected several differences in the relative size of separate brain regions across feeding treatments, sexes and mating strategies. For instance, the relative size of the cognitive centre of the brain, the telencephalon, was largest in sneaker males. Our data support that a large relative brain size is maintained in individuals that start reproduction early also during fast body growth. We propose that the cognitive demands during complex mating behaviours maintain a high level of investment into brain development in reproducing individuals.

Brain Imaging of Human Sexual Response: Recent Developments and Future Directions.

PubMed

Ruesink, Gerben B; Georgiadis, Janniko R

2017-01-01

The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Stable patterns of brain activation have been established for different phases of the sexual response, especially with regard to the wanting phase, and changes in these patterns can be linked to sexual response variations, including sexual dysfunctions. From this solid basis, connectivity studies of the human sexual response have begun to add a deeper understanding of the brain network function and structure involved. The study of "sexual" brain connectivity is still very young. Yet, by approaching the brain as a connected organ, the essence of brain function is captured much more accurately, increasing the likelihood of finding useful biomarkers and targets for intervention in sexual dysfunction.

Role of von Willebrand Factor and ADAMTS13 in early brain injury after experimental subarachnoid hemorrhage.

PubMed

Wan, H; Wang, Y; Ai, J; Brathwaite, S; Ni, H; Macdonald, R L; Hol, E M; Meijers, J C M; Vergouwen, M D I

2018-05-05

Early brain injury is an important determinant of poor functional outcome and case-fatality after aneurysmal subarachnoid hemorrhage (SAH) and associated with early platelet aggregation. No treatment exists for early brain injury after SAH. We investigated if von Willebrand Factor (VWF) is involved in the pathogenesis of early brain injury, and if ultra-early treatment with recombinant ADAMTS13 (rADAMTS13) reduces early brain injury after experimental SAH. Experimental SAH in mice was induced by prechiasmatic injection of non-anticoagulated blood from a littermate. The following experimental SAH groups were investigated: C57BL/6J control (n=21), VWF -/- (n=25), ADAMTS13 -/- (n=23), and C57BL/6J treated with rADAMTS13 (n=26). Mice were sacrificed at 2 hours post-SAH. Primary outcome measures were microglial activation (Iba-1 surface area) and neuronal injury (number of cleaved caspase-3 positive neurons). Compared with controls, microglial activation was decreased in VWF -/- mice (mean difference -20.0%; 95% CI: -4.0% to -38.6%), increased in ADAMTS13 -/- mice (mean difference +34.0%; 95% CI: 16.2% to 51.7%), and decreased in rADAMTS13 treated mice (mean difference -22.1%; 95% CI: -3.4% to -39.1%). Compared with controls (185 neurons [IQR 133-353]), neuronal injury in the cerebral cortex was decreased in VWF -/- mice (63 neurons [IQR 25-78]), not changed in ADAMTS13 -/- mice (53 neurons [IQR 26-221]), and reduced in rADAMTS13 treated mice (45 neurons [IQR 9-115]). Our findings suggest that VWF is involved in the pathogenesis of early brain injury and support the further study of rADAMTS13 as a treatment option for early brain injury after SAH. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Premature brain aging in humans exposed to maternal nutrient restriction during early gestation.

PubMed

Franke, Katja; Gaser, Christian; Roseboom, Tessa J; Schwab, Matthias; de Rooij, Susanne R

2018-06-01

Prenatal exposure to undernutrition is widespread in both developing and industrialized countries, causing irreversible damage to the developing brain, resulting in altered brain structure and decreased cognitive function during adulthood. The Dutch famine in 1944/45 was a humanitarian disaster, now enabling studies of the effects of prenatal undernutrition during gestation on brain aging in late adulthood. We hypothesized that study participants prenatally exposed to maternal nutrient restriction (MNR) would demonstrate altered brain structure resembling premature brain aging in late adulthood, expecting the effect being stronger in men. Utilizing the Dutch famine birth cohort (n = 118; mean age: 67.5 ± 0.9 years), this study implements an innovative biomarker for individual brain aging, using structural neuroimaging. BrainAGE was calculated using state-of-the-art pattern recognition methods, trained on an independent healthy reference sample, then applied to the Dutch famine MRI sample, to evaluate the effects of prenatal undernutrition during early gestation on individual brain aging in late adulthood. Exposure to famine in early gestation was associated with BrainAGE scores indicative of an older-appearing brain in the male sample (mean difference to subjects born before famine: 4.3 years, p < 0.05). Furthermore, in explaining the observed variance in individual BrainAGE scores in the male sample, maternal age at birth, head circumference at birth, medical treatment of hypertension, history of cerebral incidences, actual heart rate, and current alcohol intake emerged to be the most influential variables (adjusted R 2  = 0.63, p < 0.01). The findings of our study on exposure to prenatal undernutrition being associated with a status of premature brain aging during late adulthood, as well as individual brain structure being shaped by birth- and late-life health characteristics, are strongly supporting the critical importance of sufficient nutrient

Inflammatory Responses in Brain Ischemia

PubMed Central

Kawabori, Masahito; Yenari, Midori A.

2017-01-01

Brain infarction causes tissue death by ischemia due to occlusion of the cerebral vessels and recent work has shown that post stroke inflammation contributes significantly to the development of ischemic pathology. Because secondary damage by brain inflammation may have a longer therapeutic time window compared to the rescue of primary damage following arterial occlusion, controlling inflammation would be an obvious therapeutic target. A substantial amount of experimentall progress in this area has been made in recent years. However, it is difficult to elucidate the precise mechanisms of the inflammatory responses following ischemic stroke because inflammation is a complex series of interactions between inflammatory cells and molecules, all of which could be either detrimental or beneficial. We review recent advances in neuroinflammation and the modulation of inflammatory signaling pathways in brain ischemia. Potential targets for treatment of ischemic stroke will also be covered. The roles of the immune system and brain damage versus repair will help to clarify how immune modulation may treat stroke. PMID:25666795

Necrostatin-1 attenuates early brain injury after subarachnoid hemorrhage in rats by inhibiting necroptosis.

PubMed

Chen, Fuxiang; Su, Xingfen; Lin, Zhangya; Lin, Yuanxiang; Yu, Lianghong; Cai, Jiawei; Kang, Dezhi; Hu, Liwen

2017-01-01

Necroptosis is programmed cell death that has been recently proposed and reported to be involved in several neurologic diseases. However, the role of necroptosis in early brain injury after subarachnoid hemorrhage (SAH) is still unknown. The purpose of this study was to investigate whether necroptosis was involved in SAH-induced early brain injury, and to assess the possible neuroprotective effect of necrostatin-1 using an endovascular perforation rat model of SAH. Our results showed that the expression levels of necroptosis-related proteins including RIP1, RIP3 and MLKL in the basal cortex all increased at 3 hours after SAH ( P <0.05) and peaked at 48 hours after SAH ( P <0.05). However, they were greatly reduced after treatment with necrostatin-1 ( P <0.05). Concurrently, neurologic outcomes were significantly improved after necrostatin-1 treatment ( P <0.05). Furthermore, brain edema, blood-brain barrier disruption, necrotic cell death and neuroinflammation were also greatly inhibited after necrostatin-1 treatment. These results indicate that necroptosis is an important mechanism of cell death involved in the early brain injury after experimental SAH. Necrostatin-1 perhaps can serve as a promising neuroprotective agent for SAH treatment.

Development of a Human Neurovascular Unit Organotypic Systems Model of Early Brain Development

EPA Science Inventory

The inability to model human brain and blood-brain barrier development in vitro poses a major challenge in studies of how chemicals impact early neurogenic periods. During human development, disruption of thyroid hormone (TH) signaling is related to adverse morphological effects ...

Human Traumatic Brain Injury Induces Autoantibody Response against Glial Fibrillary Acidic Protein and Its Breakdown Products

PubMed Central

Mondello, Stefania; Newsom, Kimberly J.; Yang, Zhihui; Yang, Boxuan; Kobeissy, Firas; Guingab, Joy; Glushakova, Olena; Robicsek, Steven; Heaton, Shelley; Buki, Andras; Hannay, Julia; Gold, Mark S.; Rubenstein, Richard; Lu, Xi-chun May; Dave, Jitendra R.; Schmid, Kara; Tortella, Frank; Robertson, Claudia S.; Wang, Kevin K. W.

2014-01-01

The role of systemic autoimmunity in human traumatic brain injury (TBI) and other forms of brain injuries is recognized but not well understood. In this study, a systematic investigation was performed to identify serum autoantibody responses to brain-specific proteins after TBI in humans. TBI autoantibodies showed predominant immunoreactivity against a cluster of bands from 38–50 kDa on human brain immunoblots, which were identified as GFAP and GFAP breakdown products. GFAP autoantibody levels increased by 7 days after injury, and were of the IgG subtype predominantly. Results from in vitro tests and rat TBI experiments also indicated that calpain was responsible for removing the amino and carboxyl termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody staining co-localized with GFAP in injured rat brain and in primary rat astrocytes. These results suggest that GFAP breakdown products persist within degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter living astroglia cells in culture and its presence appears to compromise glial cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP autoantibody levels from early (0–1 days) to late (7–10 days) times post injury. Changes in autoantibody levels were negatively correlated with outcome as measured by GOS-E score at 6 months, suggesting that TBI patients with greater anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients. PMID:24667434

Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for psychopathology

PubMed Central

Booij, Linda; Tremblay, Richard E.; Szyf, Moshe; Benkelfat, Chawki

2015-01-01

Background Despite more than 60 years of research in the role of serotonin (5-HT) in psychopathology, many questions still remain. From a developmental perspective, studies have provided more insight into how 5-HT dysfunctions acquired in utero or early in life may modulate brain development. This paper discusses the relevance of the developmental role of 5-HT for the understanding of psychopathology. We review developmental milestones of the 5-HT system, how genetic and environmental 5-HT disturbances could affect brain development and the potential role of DNA methylation in 5-HT genes for brain development. Methods Studies were identified using common databases (e.g., PubMed, Google Scholar) and reference lists. Results Despite the widely supported view that the 5-HT system matures in early life, different 5-HT receptors, proteins and enzymes have different developmental patterns, and development is brain region–specific. A disruption in 5-HT homeostasis during development may lead to structural and functional changes in brain circuits that modulate emotional stress responses, including subcortical limbic and (pre)frontal areas. This may result in a predisposition to psychopathology. DNA methylation might be one of the underlying physiologic mechanisms. Limitations There is a need for prospective studies. The impact of stressors during adolescence on the 5-HT system is understudied. Questions regarding efficacy of drugs acting on 5-HT still remain. Conclusion A multidisciplinary and longitudinal approach in designing studies on the role of 5-HT in psychopathology might help to bring us closer to the understanding of the role of 5-HT in psychopathology. PMID:25285876

Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure.

PubMed

Barbier, Estelle; Pierrefiche, Olivier; Vaudry, David; Vaudry, Hubert; Daoust, Martine; Naassila, Mickaël

2008-12-01

Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring.

A review on neuroimaging studies of genetic and environmental influences on early brain development.

PubMed

Gao, Wei; Grewen, Karen; Knickmeyer, Rebecca C; Qiu, Anqi; Salzwedel, Andrew; Lin, Weili; Gilmore, John H

2018-04-16

The past decades witnessed a surge of interest in neuroimaging study of normal and abnormal early brain development. Structural and functional studies of normal early brain development revealed massive structural maturation as well as sequential, coordinated, and hierarchical emergence of functional networks during the infancy period, providing a great foundation for the investigation of abnormal early brain development mechanisms. Indeed, studies of altered brain development associated with either genetic or environmental risks emerged and thrived. In this paper, we will review selected studies of genetic and environmental risks that have been relatively more extensively investigated-familial risks, candidate risk genes, and genome-wide association studies (GWAS) on the genetic side; maternal mood disorders and prenatal drug exposures on the environmental side. Emerging studies on environment-gene interactions will also be reviewed. Our goal was not to perform an exhaustive review of all studies in the field but to leverage some representative ones to summarize the current state, point out potential limitations, and elicit discussions on important future directions. Copyright © 2018 Elsevier Inc. All rights reserved.

The relationship between age and brain response to visual erotic stimuli in healthy heterosexual males.

PubMed

Seo, Y; Jeong, B; Kim, J-W; Choi, J

2010-01-01

The various changes of sexuality, including decreased sexual desire and erectile dysfunction, are also accompanied with aging. To understand the effect of aging on sexuality, we explored the relationship between age and the visual erotic stimulation-related brain response in sexually active male subjects. Twelve healthy, heterosexual male subjects (age 22-47 years) were recorded the functional magnetic resonance imaging (fMRI) signals of their brain activation elicited by passive viewing erotic (ERO), happy-faced (HA) couple, food and nature pictures. Mixed effect analysis and correlation analysis were performed to investigate the relationship between the age and the change of brain activity elicited by erotic stimuli. Our results showed age was positively correlated with the activation of right occipital fusiform gyrus and amygdala, and negatively correlated with the activation of right insula and inferior frontal gyrus. These findings suggest age might be related with functional decline in brain regions being involved in both interoceptive sensation and prefrontal modulation while it is related with the incremental activity of the brain region for early processing of visual emotional stimuli in sexually healthy men.

Brain Arteriovenous Malformation Pathogenesis: A Response-to-Injury Paradigm

PubMed Central

Kim, Helen; Su, Hua; Weinsheimer, Shantel; Pawlikowska, Ludmila; Young, William L.

2011-01-01

Brain arteriovenous malformations (AVMs) are a rare but important cause of intracranial hemorrhage (ICH) in young adults. In this paper, we review both human and animal studies of brain AVM, focusing on the: (1) natural history of AVM hemorrhage; (2) genetic and expression studies of AVM susceptibility and hemorrhage; and (3) strategies for development of a brain AVM model in adult mice. These data target various mechanisms which must act in concert to regulate normal angiogenic response to injury. Based on the various lines of evidence reviewed in this paper, we propose a “response-to-injury” model of brain AVM pathogenesis. PMID:21725736

Lipopolysaccharide hyporesponsiveness: protective or damaging response to the brain?

PubMed

Pardon, Marie Christine

2015-01-01

Lipopolysaccharide (LPS) endotoxins are widely used as experimental models of systemic bacterial infection and trigger robust inflammation by potently activating toll-like receptors 4 (TLR4) expressed on innate immune cells. Their ability to trigger robust neuroinflammation despite poor brain penetration can prove useful for the understanding of how inflammation induced by viral infections contributes to the pathogenesis of neurodegenerative diseases. A single LPS challenge often result in a blunted inflammatory response to subsequent stimulation by LPS and other TLR ligands, but the extent to which endotoxin tolerance occur in the brain requires further clarification. LPS is also thought to render the brain transiently resistant to subsequent brain injuries by attenuating the concomitant pro-inflammatory response. While LPS hyporesponsiveness and preconditioning are classically seen as protective mechanisms limiting the toxic effects of sustained inflammation, recent research casts doubt as to whether they have beneficial or detrimental roles on the brain and in neurodegenerative disease. These observations suggest that spatio-temporal aspects of the immune responses to LPS and the disease status are determinant factors. Endotoxin tolerance may lead to a late pro-inflammatory response with potential harmful consequences. And while reduced TLR4 signaling reduces the risk of neurodegenerative diseases, up-regulation of anti-inflammatory cytokines associated with LPS hyporesponsiveness can have deleterious consequences to the brain by inhibiting the protective phenotype of microglia, aggravating the progression of some neurodegenerative conditions such as Alzheimer's disease. Beneficial effects of LPS preconditioning, however appear to require a stimulation of anti-inflammatory mediators rather than an attenuation of the pro-inflammatory response.

A new rabbit model for the study of early brain injury after subarachnoid hemorrhage.

PubMed

Marbacher, Serge; Andereggen, Lukas; Neuschmelting, Volker; Widmer, Hans Rudolf; von Gunten, Michael; Takala, Jukka; Jakob, Stephan M; Fandino, Javier

2012-07-15

Pathophysiological disturbances during subarachnoid hemorrhage (SAH) and within the first few days thereafter are responsible for significant brain damage. Early brain injury (EBI) after SAH has become the focus of current research activities. The purpose of the present study was to evaluate whether a novel rabbit SAH model provokes EBI by means of neuronal degeneration, brain tissue death, and apoptosis in cerebral vascular endothelial cells. SAH was performed using an extra-intracranial blood shunt. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and bilateral regional cerebral blood flow (rCBF) were continuously measured. Apoptosis and neurodegeneration were detected 24h post-SAH in basilar artery endothelial cells, bilateral basal cortex, and hippocampus (CA1 and CA3) using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB), respectively. ICP increase caused a CPP decrease to almost zero (8±5mmHg) and decreases in left and right rCBF to 23±8% and 19±9% of their baseline values. TUNEL- and FJB-stained sections revealed significant apoptosis and neurodegeneration in both basal cortex and hippocampal regions compared to sham-operated animals. The apoptotic index in basilar artery endothelial cells was 74%±11%. The blood shunt rabbit SAH model elicits acute physiological dearrangements and provokes marked and consistent early damage to the hippocampus, basal cortex, and cerebral vasculature 24h thereafter. These findings make the model a valid tool for investigation of pre-vasospasm pathophysiological mechanisms and novel treatment modalities. Copyright © 2012 Elsevier B.V. All rights reserved.

Brain metabolite alterations and cognitive dysfunction in early Huntington’s Disease

PubMed Central

Unschuld, Paul G.; Edden, Richard A. E.; Carass, Aaron; Liu, Xinyang; Shanahan, Megan; Wang, Xin; Oishi, Kenichi; Brandt, Jason; Bassett, Susan S.; Redgrave, Graham W.; Margolis, Russell L.; van Zijl, Peter C. M.; Barker, Peter B.; Ross, Christopher A.

2012-01-01

Background Huntington’s Disease (HD) is a neurodegenerative disorder characterized by early cognitive decline, which progresses at later stages to dementia and severe movement disorder. HD is caused by a cytosine-adenine-guanine triplet-repeat expansion mutation in the Huntingtin gene, allowing early diagnosis by genetic testing. This study aims to identify the relationship of N-acetylaspartate and other brain metabolites to cognitive function in HD-mutation carriers by using high field strength magnetic-resonance-spectroscopy at 7-Tesla. Methods Twelve individuals with the HD-mutation in premanifest or early stage of disease versus twelve healthy controls underwent 1H magnetic-resonance-spectroscopy (7.2ml voxel in the posterior cingulate cortex) at 7-Tesla, and also T1-weighted structural magnetic-resonance-imaging. All participants received standardized tests of cognitive functioning including the Montreal Cognitive Assessment and standardized quantified neurological examination within an hour before scanning. Results Individuals with the HD mutation had significantly lower posterior cingulate cortex N-acetylaspartate (−9.6%, p=0.02) and glutamate levels (−10.1%, p=0.02) than controls. By contrast, in this small group, measures of brain morphology including striatal and ventricle volumes did not differ significantly. Linear regression with Montreal Cognitive Assessment scores revealed significant correlations with N-acetylaspartate (r2=0.50, p=0.01) and glutamate (r2=0.64, p=0.002) in HD subjects. Conclusions Our data suggest a relationship between reduced N-acetylaspartate and glutamate levels in the posterior cingulate cortex with cognitive decline in early stages of HD. N-acetylaspartate and glutamate magnetic-resonance-spectroscopy signals of the posterior cingulate cortex region may serve as potential biomarkers of disease progression or treatment outcome in HD and other neurodegenerative disorders with early cognitive dysfunction, when structural

Reversing the Real Brain Drain: Early Years Study--A Response.

ERIC Educational Resources Information Center

Killoran, Isabel

2001-01-01

Presents concerns over the "Early Years Study" (McCain & Mustard). Focuses on diversity issues related to the readiness measure used, parenting styles, and the importance of first language development. Questions the report's definition of "developmentally-attuned." Concludes by expressing hope that the Early Years Study…

Inter-subject synchronization of brain responses during natural music listening

PubMed Central

Abrams, Daniel A.; Ryali, Srikanth; Chen, Tianwen; Chordia, Parag; Khouzam, Amirah; Levitin, Daniel J.; Menon, Vinod

2015-01-01

Music is a cultural universal and a rich part of the human experience. However, little is known about common brain systems that support the processing and integration of extended, naturalistic ‘real-world’ music stimuli. We examined this question by presenting extended excerpts of symphonic music, and two pseudomusical stimuli in which the temporal and spectral structure of the Natural Music condition were disrupted, to non-musician participants undergoing functional brain imaging and analysing synchronized spatiotemporal activity patterns between listeners. We found that music synchronizes brain responses across listeners in bilateral auditory midbrain and thalamus, primary auditory and auditory association cortex, right-lateralized structures in frontal and parietal cortex, and motor planning regions of the brain. These effects were greater for natural music compared to the pseudo-musical control conditions. Remarkably, inter-subject synchronization in the inferior colliculus and medial geniculate nucleus was also greater for the natural music condition, indicating that synchronization at these early stages of auditory processing is not simply driven by spectro-temporal features of the stimulus. Increased synchronization during music listening was also evident in a right-hemisphere fronto-parietal attention network and bilateral cortical regions involved in motor planning. While these brain structures have previously been implicated in various aspects of musical processing, our results are the first to show that these regions track structural elements of a musical stimulus over extended time periods lasting minutes. Our results show that a hierarchical distributed network is synchronized between individuals during the processing of extended musical sequences, and provide new insight into the temporal integration of complex and biologically salient auditory sequences. PMID:23578016

Inter-subject synchronization of brain responses during natural music listening.

PubMed

Abrams, Daniel A; Ryali, Srikanth; Chen, Tianwen; Chordia, Parag; Khouzam, Amirah; Levitin, Daniel J; Menon, Vinod

2013-05-01

Music is a cultural universal and a rich part of the human experience. However, little is known about common brain systems that support the processing and integration of extended, naturalistic 'real-world' music stimuli. We examined this question by presenting extended excerpts of symphonic music, and two pseudomusical stimuli in which the temporal and spectral structure of the Natural Music condition were disrupted, to non-musician participants undergoing functional brain imaging and analysing synchronized spatiotemporal activity patterns between listeners. We found that music synchronizes brain responses across listeners in bilateral auditory midbrain and thalamus, primary auditory and auditory association cortex, right-lateralized structures in frontal and parietal cortex, and motor planning regions of the brain. These effects were greater for natural music compared to the pseudo-musical control conditions. Remarkably, inter-subject synchronization in the inferior colliculus and medial geniculate nucleus was also greater for the natural music condition, indicating that synchronization at these early stages of auditory processing is not simply driven by spectro-temporal features of the stimulus. Increased synchronization during music listening was also evident in a right-hemisphere fronto-parietal attention network and bilateral cortical regions involved in motor planning. While these brain structures have previously been implicated in various aspects of musical processing, our results are the first to show that these regions track structural elements of a musical stimulus over extended time periods lasting minutes. Our results show that a hierarchical distributed network is synchronized between individuals during the processing of extended musical sequences, and provide new insight into the temporal integration of complex and biologically salient auditory sequences. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Impaired early visual response modulations to spatial information in chronic schizophrenia

PubMed Central

Knebel, Jean-François; Javitt, Daniel C.; Murray, Micah M.

2011-01-01

Early visual processing stages have been demonstrated to be impaired in schizophrenia patients and their first-degree relatives. The amplitude and topography of the P1 component of the visual evoked potential (VEP) are both affected; the latter of which indicates alterations in active brain networks between populations. At least two issues remain unresolved. First, the specificity of this deficit (and suitability as an endophenotype) has yet to be established, with evidence for impaired P1 responses in other clinical populations. Second, it remains unknown whether schizophrenia patients exhibit intact functional modulation of the P1 VEP component; an aspect that may assist in distinguishing effects specific to schizophrenia. We applied electrical neuroimaging analyses to VEPs from chronic schizophrenia patients and healthy controls in response to variation in the parafoveal spatial extent of stimuli. Healthy controls demonstrated robust modulation of the VEP strength and topography as a function of the spatial extent of stimuli during the P1 component. By contrast, no such modulations were evident at early latencies in the responses from patients with schizophrenia. Source estimations localized these deficits to the left precuneus and medial inferior parietal cortex. These findings provide insights on potential underlying low-level impairments in schizophrenia. PMID:21764264

Nanotheranostics: Emerging Strategies for Early Diagnosis and Therapy of Brain Cancer

PubMed Central

Sonali; Viswanadh, Matte Kasi; Singh, Rahul Pratap; Agrawal, Poornima; Mehata, Abhishesh Kumar; Pawde, Datta Maroti; Narendra; Sonkar, Roshan; Muthu, Madaswamy Sona

2018-01-01

Nanotheranostics have demonstrated the development of advanced platforms that can diagnose brain cancer at early stages, initiate first-line therapy, monitor it, and if needed, rapidly start subsequent treatments. In brain nanotheranostics, therapeutic as well as diagnostic entities are loaded in a single nanoplatform, which can be further developed as a clinical formulation for targeting various modes of brain cancer. In the present review, we concerned about theranostic nanosystems established till now in the research field. These include gold nanoparticles, carbon nanotubes, magnetic nanoparticles, mesoporous silica nanoparticles, quantum dots, polymeric nanoparticles, upconversion nanoparticles, polymeric micelles, solid lipid nanoparticles and dendrimers for the advanced detection and treatment of brain cancer with advanced features. Also, we included the role of three-dimensional models of the BBB and cancer stem cell concept for the advanced characterization of nanotheranostic systems for the unification of diagnosis and treatment of brain cancer. In future, brain nanotheranostics will be able to provide personalized treatment which can make brain cancer even remediable or at least treatable at the primary stages. PMID:29291164

Auditory brain development in premature infants: the importance of early experience.

PubMed

McMahon, Erin; Wintermark, Pia; Lahav, Amir

2012-04-01

Preterm infants in the neonatal intensive care unit (NICU) often close their eyes in response to bright lights, but they cannot close their ears in response to loud sounds. The sudden transition from the womb to the overly noisy world of the NICU increases the vulnerability of these high-risk newborns. There is a growing concern that the excess noise typically experienced by NICU infants disrupts their growth and development, putting them at risk for hearing, language, and cognitive disabilities. Preterm neonates are especially sensitive to noise because their auditory system is at a critical period of neurodevelopment, and they are no longer shielded by maternal tissue. This paper discusses the developmental milestones of the auditory system and suggests ways to enhance the quality control and type of sounds delivered to NICU infants. We argue that positive auditory experience is essential for early brain maturation and may be a contributing factor for healthy neurodevelopment. Further research is needed to optimize the hospital environment for preterm newborns and to increase their potential to develop into healthy children. © 2012 New York Academy of Sciences.

The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants.

PubMed

Dubois, J; Dehaene-Lambertz, G; Kulikova, S; Poupon, C; Hüppi, P S; Hertz-Pannier, L

2014-09-12

Studying how the healthy human brain develops is important to understand early pathological mechanisms and to assess the influence of fetal or perinatal events on later life. Brain development relies on complex and intermingled mechanisms especially during gestation and first post-natal months, with intense interactions between genetic, epigenetic and environmental factors. Although the baby's brain is organized early on, it is not a miniature adult brain: regional brain changes are asynchronous and protracted, i.e. sensory-motor regions develop early and quickly, whereas associative regions develop later and slowly over decades. Concurrently, the infant/child gradually achieves new performances, but how brain maturation relates to changes in behavior is poorly understood, requiring non-invasive in vivo imaging studies such as magnetic resonance imaging (MRI). Two main processes of early white matter development are reviewed: (1) establishment of connections between brain regions within functional networks, leading to adult-like organization during the last trimester of gestation, (2) maturation (myelination) of these connections during infancy to provide efficient transfers of information. Current knowledge from post-mortem descriptions and in vivo MRI studies is summed up, focusing on T1- and T2-weighted imaging, diffusion tensor imaging, and quantitative mapping of T1/T2 relaxation times, myelin water fraction and magnetization transfer ratio. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Alteration of diffusion-tensor MRI measures in brain regions involved in early stages of Parkinson's disease.

PubMed

Chen, Nan-Kuei; Chou, Ying-Hui; Sundman, Mark; Hickey, Patrick; Kasoff, Willard S; Bernstein, Adam; Trouard, Theodore P; Lin, Tanya; Rapcsak, Steven Z; Sherman, Scott J; Weingarten, Carol

2018-06-07

Many non-motor symptoms (e.g., hyposmia) appear years before the cardinal motor features of Parkinson's disease (PD). It is thus desirable to be able to use noninvasive brain imaging methods, such as magnetic resonance imaging (MRI), to detect brain abnormalities in early PD stages. Among the MRI modalities, diffusion tensor imaging (DTI) is suitable for detecting changes of brain tissue structure due to neurological diseases. The main purpose of this study was to investigate whether DTI signals measured from brain regions involved in early stages of PD differ from those of healthy controls. To answer this question, we analyzed whole-brain DTI data of 30 early-stage PD patients and 30 controls using improved ROI based analysis methods. Results showed that 1) the fractional anisotropy (FA) values in the olfactory tract (connected with the olfactory bulb: one of the first structures affected by PD) are lower in PD patients than healthy controls; 2) FA values are higher in PD patients than healthy controls in the following brain regions: corticospinal tract, cingulum (near hippocampus), and superior longitudinal fasciculus (temporal part). Experimental results suggest that the tissue property, measured by FA, in olfactory regions is structurally modulated by PD with a mechanism that is different from other brain regions.

Human brain spots emotion in non humanoid robots

PubMed Central

Foucher, Aurélie; Jouvent, Roland; Nadel, Jacqueline

2011-01-01

The computation by which our brain elaborates fast responses to emotional expressions is currently an active field of brain studies. Previous studies have focused on stimuli taken from everyday life. Here, we investigated event-related potentials in response to happy vs neutral stimuli of human and non-humanoid robots. At the behavioural level, emotion shortened reaction times similarly for robotic and human stimuli. Early P1 wave was enhanced in response to happy compared to neutral expressions for robotic as well as for human stimuli, suggesting that emotion from robots is encoded as early as human emotion expression. Congruent with their lower faceness properties compared to human stimuli, robots elicited a later and lower N170 component than human stimuli. These findings challenge the claim that robots need to present an anthropomorphic aspect to interact with humans. Taken together, such results suggest that the early brain processing of emotional expressions is not bounded to human-like arrangements embodying emotion. PMID:20194513

Early primary biliary cholangitis is characterised by brain abnormalities on cerebral magnetic resonance imaging.

PubMed

Grover, V P B; Southern, L; Dyson, J K; Kim, J U; Crossey, M M E; Wylezinska-Arridge, M; Patel, N; Fitzpatrick, J A; Bak-Bol, A; Waldman, A D; Alexander, G J; Mells, G F; Chapman, R W; Jones, D E J; Taylor-Robinson, S D

2016-11-01

Brain change can occur in primary biliary cholangitis (PBC), potentially as a result of cholestatic and/or inflammatory processes. This change is linked to systemic symptoms of fatigue and cognitive impairment. To identify whether brain change occurs early in PBC. If the change develops early and is progressive, it may explain the difficulty in treating these symptoms. Early disease brain change was explored in 13 patients with newly diagnosed biopsy-proven precirrhotic PBC using magnetisation transfer, diffusion-weighted imaging and 1 H magnetic resonance spectroscopy. Results were compared to 17 healthy volunteers. Cerebral magnetisation transfer ratios were reduced in early PBC, compared to healthy volunteers, in the thalamus, putamen and head of caudate with no greater reduction in patients with greater symptom severity. Mean apparent diffusion coefficients were increased in the thalamus only. No 1 H magnetic resonance spectroscopy abnormalities were seen. Serum manganese levels were elevated in all PBC patients, but no relationship was seen with imaging or symptom parameters. There were no correlations between neuroimaging data, laboratory data, symptom severity scores or age. This is the first study to be performed in this precirrhotic patient population, and we have highlighted that neuroimaging changes are present at a much earlier stage than previously demonstrated. The neuroimaging abnormalities suggest that the brain changes seen in PBC occur early in the pathological process, even before significant liver damage has occurred. If such changes are linked to symptom pathogenesis, this could have important implications for the timing of second-line-therapy use. © 2016 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Alterations in Sociability and Functional Brain Connectivity Caused by Early-Life Seizures is Reversed by Bumetanide

PubMed Central

Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy

2015-01-01

There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) day 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure

Early Life Stress Differentially Modulates Distinct Forms of Brain Plasticity in Young and Adult Mice

PubMed Central

Reichardt, Wilfried; Clark, Kristin; Geiger, Julia; Gross, Claus M.; Heyer, Andrea; Neagu, Valentin; Bhatia, Harsharan; Atas, Hasan C.; Fiebich, Bernd L.; Bischofberger, Josef; Haas, Carola A.; Normann, Claus

2012-01-01

Background Early life trauma is an important risk factor for many psychiatric and somatic disorders in adulthood. As a growing body of evidence suggests that brain plasticity is disturbed in affective disorders, we examined the short-term and remote effects of early life stress on different forms of brain plasticity. Methodology/Principal Findings Mice were subjected to early deprivation by individually separating pups from their dam in the first two weeks after birth. Distinct forms of brain plasticity were assessed in the hippocampus by longitudinal MR volumetry, immunohistochemistry of neurogenesis, and whole-cell patch-clamp measurements of synaptic plasticity. Depression-related behavior was assessed by the forced swimming test in adult animals. Neuropeptides and their receptors were determined by real-time PCR and immunoassay. Early maternal deprivation caused a loss of hippocampal volume, which returned to normal in adulthood. Adult neurogenesis was unaffected by early life stress. Long-term synaptic potentiation, however, was normal immediately after the end of the stress protocol but was impaired in adult animals. In the forced swimming test, adult animals that had been subjected to early life stress showed increased immobility time. Levels of substance P were increased both in young and adult animals after early deprivation. Conclusion Hippocampal volume was affected by early life stress but recovered in adulthood which corresponded to normal adult neurogenesis. Synaptic plasticity, however, exhibited a delayed impairment. The modulation of synaptic plasticity by early life stress might contribute to affective dysfunction in adulthood. PMID:23071534

Early (N170/M170) Face-Sensitivity Despite Right Lateral Occipital Brain Damage in Acquired Prosopagnosia

PubMed Central

Prieto, Esther Alonso; Caharel, Stéphanie; Henson, Richard; Rossion, Bruno

2011-01-01

Compared to objects, pictures of faces elicit a larger early electromagnetic response at occipito-temporal sites on the human scalp, with an onset of 130 ms and a peak at about 170 ms. This N170 face effect is larger in the right than the left hemisphere and has been associated with the early categorization of the stimulus as a face. Here we tested whether this effect can be observed in the absence of some of the visual areas showing a preferential response to faces as typically identified in neuroimaging. Event-related potentials were recorded in response to faces, cars, and their phase-scrambled versions in a well-known brain-damaged case of prosopagnosia (PS). Despite the patient’s right inferior occipital gyrus lesion encompassing the most posterior cortical area showing preferential response to faces (“occipital face area”), we identified an early face-sensitive component over the right occipito-temporal hemisphere of the patient that was identified as the N170. A second experiment supported this conclusion, showing the typical N170 increase of latency and amplitude in response to inverted faces. In contrast, there was no N170 in the left hemisphere, where PS has a lesion to the middle fusiform gyrus and shows no evidence of face-preferential response in neuroimaging (no left “fusiform face area”). These results were replicated by a magnetoencephalographic investigation of the patient, disclosing a M170 component only in the right hemisphere. These observations indicate that face-preferential activation in the inferior occipital cortex is not necessary to elicit early visual responses associated with face perception (N170/M170) on the human scalp. These results further suggest that when the right inferior occipital cortex is damaged, the integrity of the middle fusiform gyrus and/or the superior temporal sulcus – two areas showing face-preferential responses in the patient’s right hemisphere – might be necessary to generate the N170 effect

Traumatic Brain Injury in Early Childhood: Developmental Effects and Interventions.

ERIC Educational Resources Information Center

Lowenthal, Barbara; Lowenthal, Barbara

1998-01-01

Describes the unique effects of traumatic brain injury (TBI) on development in early childhood and offers suggestions for interventions in the cognitive, language, social-emotional, motor, and adaptive domains. Urges more intensive, long-term studies on the immediate and long-term effects of TBI. (Author/DB)

Early functional and morphological brain disturbances in late-onset intrauterine growth restriction.

PubMed

Starčević, Mirta; Predojević, Maja; Butorac, Dražan; Tumbri, Jasna; Konjevoda, Paško; Kadić, Aida Salihagić

2016-02-01

To determine whether the brain disturbances develop in late-onset intrauterine growth restriction (IUGR) before blood flow redistribution towards the fetal brain (detected by Doppler measurements in the middle cerebral artery and umbilical artery). Further, to evaluate predictive values of Doppler arterial indices and umbilical cord blood gases and pH for early functional and/or morphological brain disturbances in late-onset IUGR. This cohort study included 60 singleton term pregnancies with placental insufficiency caused late-onset IUGR (IUGR occurring after 34 gestational weeks). Umbilical artery resistance index (URI), middle cerebral artery resistance index (CRI), and cerebroumbilical (C/U) ratio (CRI/URI) were monitored once weekly. Umbilical blood cord samples (arterial and venous) were collected for the analysis of pO2, pCO2 and pH. Morphological neurological outcome was evaluated by cranial ultrasound (cUS), whereas functional neurological outcome by Amiel-Tison Neurological Assessment at Term (ATNAT). 50 fetuses had C/U ratio>1, and 10 had C/U ratio≤1; among these 10 fetuses, 9 had abnormal neonatal cUS findings and all 10 had non-optimal ATNAT. However, the total number of abnormal neurological findings was much higher. 32 neonates had abnormal cUS (53.37%), and 42 (70.00%) had non-optimal ATNAT. Furthermore, Doppler indices had higher predictive validity for early brain disturbances than umbilical cord blood gases and pH. C/U ratio had the highest predictive validity with threshold for adverse neurological outcome at value 1.13 (ROC analysis), i.e., 1.18 (party machine learning algorithm). Adverse neurological outcome at average values of C/U ratios>1 confirmed that early functional and/or structural brain disturbances in late-onset IUGR develop even before activation of fetal cardiovascular compensatory mechanisms, i.e., before Doppler signs of blood flow redistribution between the fetal brain and the placenta. Copyright © 2015 Elsevier Ireland Ltd

Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents

PubMed Central

Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A.; Santoro, Nicola; Savoye, Mary; Duran, Elvira J.; Pierpont, Bridget; Cline, Gary; Constable, R. Todd; Sherwin, Robert S.

2016-01-01

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. PMID:27207544

Delineation of early brain development from fetuses to infants with diffusion MRI and beyond.

PubMed

Ouyang, Minhui; Dubois, Jessica; Yu, Qinlin; Mukherjee, Pratik; Huang, Hao

2018-04-12

Dynamic macrostructural and microstructural changes take place from the mid-fetal stage to 2 years after birth. Delineating structural changes of the brain during early development provides new insights into the complicated processes of both typical development and the pathological mechanisms underlying various psychiatric and neurological disorders including autism, attention deficit hyperactivity disorder and schizophrenia. Decades of histological studies have identified strong spatial and functional maturation gradients in human brain gray and white matter. The recent improvements in magnetic resonance imaging (MRI) techniques, especially diffusion MRI (dMRI), relaxometry imaging, and magnetization transfer imaging (MTI) have provided unprecedented opportunities to non-invasively quantify and map the early developmental changes at whole brain and regional levels. Here, we review the recent advances in understanding early brain structural development during the second half of gestation and the first two postnatal years using modern MR techniques. Specifically, we review studies that delineate the emergence and microstructural maturation of white matter tracts, as well as dynamic mapping of inhomogeneous cortical microstructural organization unique to fetuses and infants. These imaging studies converge into maturational curves of MRI measurements that are distinctive across different white matter tracts and cortical regions. Furthermore, contemporary models offering biophysical interpretations of the dMRI-derived measurements are illustrated to infer the underlying microstructural changes. Collectively, this review summarizes findings that contribute to charting spatiotemporally heterogeneous gray and white matter structural development, offering MRI-based biomarkers of typical brain development and setting the stage for understanding aberrant brain development in neurodevelopmental disorders. Copyright © 2018 Elsevier Inc. All rights reserved.

Brain Mechanisms Involved in Early Visual Perception.

ERIC Educational Resources Information Center

Karmel, Bernard Z.

This document presents an analysis of the early attending responses and orienting reactions of infants which can be observed at birth and shortly thereafter. Focus is on one specific orienting reaction, the early direction and maintenance of one's eyes and head toward certain stimuli instead of others. The physical properties of stimuli that…

Early Environmental Enrichment Enhances Abnormal Brain Connectivity in a Rabbit Model of Intrauterine Growth Restriction.

PubMed

Illa, Miriam; Brito, Verónica; Pla, Laura; Eixarch, Elisenda; Arbat-Plana, Ariadna; Batallé, Dafnis; Muñoz-Moreno, Emma; Crispi, Fatima; Udina, Esther; Figueras, Francesc; Ginés, Silvia; Gratacós, Eduard

2017-10-12

The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored. IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus. IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure. IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR. © 2017 S. Karger AG, Basel.

Dosimetric evaluation of radionuclides for VCAM-1-targeted radionuclide therapy of early brain metastases.

PubMed

Falzone, Nadia; Ackerman, Nicole L; Rosales, Liset de la Fuente; Bernal, Mario A; Liu, Xiaoxuan; Peeters, Sarah Gja; Soto, Manuel Sarmiento; Corroyer-Dulmont, Aurélien; Bernaudin, Myriam; Grimoin, Elisa; Touzani, Omar; Sibson, Nicola R; Vallis, Katherine A

2018-01-01

Brain metastases develop frequently in patients with breast cancer, and present a pressing therapeutic challenge. Expression of vascular cell adhesion molecule 1 (VCAM-1) is upregulated on brain endothelial cells during the early stages of metastasis and provides a target for the detection and treatment of early brain metastases. The aim of this study was to use a model of early brain metastasis to evaluate the efficacy of α-emitting radionuclides, 149 Tb, 211 At, 212 Pb, 213 Bi and 225 Ac; β-emitting radionuclides, 90 Y, 161 Tb and 177 Lu; and Auger electron (AE)-emitters 67 Ga, 89 Zr, 111 In and 124 I, for targeted radionuclide therapy (TRT). Histologic sections and two photon microscopy of mouse brain parenchyma were used to inform a cylindrical vessel geometry using the Geant4 general purpose Monte Carlo (MC) toolkit with the Geant4-DNA low energy physics models. Energy deposition was evaluated as a radial function and the resulting phase spaces were superimposed on a DNA model to estimate double-strand break (DSB) yields for representative β- and α-emitters, 177 Lu and 212 Pb. Relative biological effectiveness (RBE) values were determined by only evaluating DNA damage due to physical interactions. 177 Lu produced 2.69 ± 0.08 DSB per GbpGy, without significant variation from the lumen of the vessel to a radius of 100 µm. The DSB yield of 212 Pb included two local maxima produced by the 6.1 MeV and 8.8 MeV α-emissions from decay products, 212 Bi and 212 Po, with yields of 7.64 ± 0.12 and 9.15 ± 0.24 per GbpGy, respectively. Given its higher DSB yield 212 Pb may be more effective for short range targeting of early micrometastatic lesions than 177 Lu. MC simulation of a model of early brain metastases provides invaluable insight into the potential efficacy of α-, β- and AE-emitting radionuclides for TRT. 212 Pb, which has the attributes of a theranostic radionuclide since it can be used for SPECT imaging, showed a favorable dose profile and RBE.

Acute and delayed neuroinflammatory response following experimental penetrating ballistic brain injury in the rat

PubMed Central

Williams, Anthony J; Wei, Hans H; Dave, Jitendra R; Tortella, Frank C

2007-01-01

Background Neuroinflammation following acute brain trauma is considered to play a prominent role in both the pathological and reconstructive response of the brain to injury. Here we characterize and contrast both an acute and delayed phase of inflammation following experimental penetrating ballistic brain injury (PBBI) in rats out to 7 days post-injury. Methods Quantitative real time PCR (QRT-PCR) was used to evaluate changes in inflammatory gene expression from the brain tissue of rats exposed to a unilateral frontal PBBI. Brain histopathology was assessed using hematoxylin and eosin (H&E), silver staining, and immunoreactivity for astrocytes (GFAP), microglia (OX-18) and the inflammatory proteins IL-1β and ICAM-1. Results Time course analysis of gene expression levels using QRT-PCR indicated a peak increase during the acute phase of the injury between 3–6 h for the cytokines TNF-α (8–11 fold), IL-1β (11–13 fold), and IL-6 (40–74 fold) as well as the cellular adhesion molecules VCAM (2–3 fold), ICAM-1 (7–15 fold), and E-selectin (11–13 fold). Consistent with the upregulation of pro-inflammatory genes, peripheral blood cell infiltration was a prominent post-injury event with peak levels of infiltrating neutrophils (24 h) and macrophages (72 h) observed throughout the core lesion. In regions of the forebrain immediately surrounding the lesion, strong immunoreactivity for activated astrocytes (GFAP) was observed as early as 6 h post-injury followed by prominent microglial reactivity (OX-18) at 72 h and resolution of both cell types in cortical brain regions by day 7. Delayed thalamic inflammation (remote from the primary lesion) was also observed as indicated by both microglial and astrocyte reactivity (72 h to 7 days) concomitant with the presence of fiber degeneration (silver staining). Conclusion In summary, PBBI induces both an acute and delayed neuroinflammatory response occurring in distinct brain regions, which may provide useful diagnostic

Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel

Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. Inmore » all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti

Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage.

PubMed

Chang, Ronald; Folkerson, Lindley E; Sloan, Duncan; Tomasek, Jeffrey S; Kitagawa, Ryan S; Choi, H Alex; Wade, Charles E; Holcomb, John B

2017-02-01

Plasma-based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large-animal and limited clinical data suggest that it also improves outcomes and is neuroprotective in the setting of combined hemorrhage and traumatic brain injury. However, the choice of initial resuscitation fluid, including the role of plasma, is unclear for patients after isolated traumatic brain injury. We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated traumatic brain injury. "Early plasma" was defined as transfusion of plasma within 4 hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and inhospital survival. After testing for interaction, subgroup analysis was performed based on the pattern of brain injury on initial head computed tomography: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage. Of the 633 isolated traumatic brain injury patients included, 178 (28%) who received early plasma were injured more severely coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% vs 84%, P = .08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio 1.18, 95% confidence interval 0.71-1.96). On subgroup analysis, multifocal intracranial hemorrhage was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4 hours. Within-group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (odds ratio 3.34, 95% confidence interval 1.20-9.35). Although early plasma transfusion was not associated with improved in-hospital survival for all isolated traumatic brain injury patients, early plasma was associated with increased in-hospital survival in those with multifocal intracranial

Food-induced brain responses and eating behaviour.

PubMed

Smeets, Paul A M; Charbonnier, Lisette; van Meer, Floor; van der Laan, Laura N; Spetter, Maartje S

2012-11-01

The brain governs food intake behaviour by integrating many different internal and external state and trait-related signals. Understanding how the decisions to start and to stop eating are made is crucial to our understanding of (maladaptive patterns of) eating behaviour. Here, we aim to (1) review the current state of the field of 'nutritional neuroscience' with a focus on the interplay between food-induced brain responses and eating behaviour and (2) highlight research needs and techniques that could be used to address these. The brain responses associated with sensory stimulation (sight, olfaction and taste), gastric distension, gut hormone administration and food consumption are the subject of increasing investigation. Nevertheless, only few studies have examined relations between brain responses and eating behaviour. However, the neural circuits underlying eating behaviour are to a large extent generic, including reward, self-control, learning and decision-making circuitry. These limbic and prefrontal circuits interact with the hypothalamus, a key homeostatic area. Target areas for further elucidating the regulation of food intake are: (eating) habit and food preference formation and modification, the neural correlates of self-control, nutrient sensing and dietary learning, and the regulation of body adiposity. Moreover, to foster significant progress, data from multiple studies need to be integrated. This requires standardisation of (neuroimaging) measures, data sharing and the application and development of existing advanced analysis and modelling techniques to nutritional neuroscience data. In the next 20 years, nutritional neuroscience will have to prove its potential for providing insights that can be used to tackle detrimental eating behaviour.

INVITED REVIEW – NEUROIMAGING RESPONSE ASSESSMENT CRITERIA FOR BRAIN TUMORS IN VETERINARY PATIENTS

PubMed Central

Rossmeisl, John H.; Garcia, Paulo A.; Daniel, Gregory B.; Bourland, John Daniel; Debinski, Waldemar; Dervisis, Nikolaos; Klahn, Shawna

2013-01-01

The evaluation of therapeutic response using cross-sectional imaging techniques, particularly gadolinium-enhanced MRI, is an integral part of the clinical management of brain tumors in veterinary patients. Spontaneous canine brain tumors are increasingly recognized and utilized as a translational model for the study of human brain tumors. However, no standardized neuroimaging response assessment criteria have been formulated for use in veterinary clinical trials. Previous studies have found that the pathophysiologic features inherent to brain tumors and the surrounding brain complicate the use of the Response Evaluation Criteria in Solid Tumors (RECIST) assessment system. Objectives of this review are to describe strengths and limitations of published imaging-based brain tumor response criteria and propose a system for use in veterinary patients. The widely used human Macdonald and Response Assessment in Neuro-oncology (RANO) criteria are reviewed and described as to how they can be applied to veterinary brain tumors. Discussion points will include current challenges associated with the interpretation of brain tumor therapeutic responses such as imaging pseudophenomena and treatment-induced necrosis, and how advancements in perfusion imaging, positron emission tomography, and magnetic resonance spectroscopy have shown promise in differentiating tumor progression from therapy-induced changes. Finally, although objective endpoints such as MR-imaging and survival estimates will likely continue to comprise the foundations for outcome measures in veterinary brain tumor clinical trials, we propose that in order to provide a more relevant therapeutic response metric for veterinary patients, composite response systems should be formulated and validated that combine imaging and clinical assessment criteria. PMID:24219161

Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour.

PubMed

Desbonnet, Lieve; Clarke, Gerard; Traplin, Alexander; O'Sullivan, Orla; Crispie, Fiona; Moloney, Rachel D; Cotter, Paul D; Dinan, Timothy G; Cryan, John F

2015-08-01

There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may

Interpersonal relationship modulates brain responses to outcome evaluation when gambling for/against others: an electrophysiological analysis.

PubMed

Leng, Yue; Zhou, Xiaolin

2014-10-01

When individuals play a gambling task and their actions have consequences for observers, how are the brain responses of the performers modulated by their interpersonal relationship with the observers? To address this issue, we examined the event-related potentials responses in performers while they played two gambling games: one during which they tried to earn money for the observers instead of themselves (i.e., Experiment 1) and another gambling game during which they attempted to earn money from the observers (i.e., Experiment 2). In Experiment 1, ERP results showed that when gambling for either the friends or the strangers, the feedback-related negativity (FRN) responses were more negative-going to the losses than to the gains. The FRN effect (loss minus gain) was significantly larger when gambling for the friends than for the strangers. The general P300 response was more positive-going when gambling for the friends than for the strangers. These results suggested that gambling for others enables individuals to assess the outcome from the interests of the other people, consequently, the FRN response may be driven by the evaluative process related to interests of the others. Because one׳s own economic interests were not involved, the performers׳ brain responses during both the early, semi-automatic stage (i.e., the FRN) and the later, controlled stage (i.e., the P300) of outcome evaluation were modulated by the interpersonal relationship between the performers and the observers. In Experiment 2, ERP results revealed that when gambling against others, the FRN response was more negative-going to the losses than to the gains, as well. However, neither the FRN effect nor the general FRN response was modulated by interpersonal relationship. The general P300 response was more positive-going when gambling against the stranger than against the friend. These results suggested that when gambling against others, the performers׳ FRN response may be driven by two evaluative

Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence.

PubMed

Humphreys, Kathryn L; Watts, Emily L; Dennis, Emily L; King, Lucy S; Thompson, Paul M; Gotlib, Ian H

2018-05-21

Despite a growing understanding that early adversity in childhood broadly affects risk for psychopathology, the contribution of stressful life events to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) is not clear. In the present study, we examined the association between number of stressful life events experienced and ADHD symptoms, assessed using the Attention Problems subscale of the Child Behavior Checklist, in a sample of 214 children (43% male) ages 9.11-13.98 years (M = 11.38, SD = 1.05). In addition, we examined whether the timing of the events (i.e., onset through age 5 years or after age 6 years) was associated with ADHD symptoms. Finally, we examined variation in brain structure to determine whether stressful life events were associated with volume in brain regions that were found to vary as a function of symptoms of ADHD. We found a small to moderate association between number of stressful life events and ADHD symptoms. Although the strength of the associations between number of events and ADHD symptoms did not differ as a function of the age of occurrence of stressful experiences, different brain regions were implicated in the association between stressors and ADHD symptoms in the two age periods during which stressful life events occurred. These findings support the hypothesis that early adversity is associated with ADHD symptoms, and provide insight into possible brain-based mediators of this association.

Endocranial morphology of Palaeocene Plesiadapis tricuspidens and evolution of the early primate brain.

PubMed

Orliac, Maeva J; Ladevèze, Sandrine; Gingerich, Philip D; Lebrun, Renaud; Smith, Thierry

2014-04-22

Expansion of the brain is a key feature of primate evolution. The fossil record, although incomplete, allows a partial reconstruction of changes in primate brain size and morphology through time. Palaeogene plesiadapoids, closest relatives of Euprimates (or crown-group primates), are crucial for understanding early evolution of the primate brain. However, brain morphology of this group remains poorly documented, and major questions remain regarding the initial phase of euprimate brain evolution. Micro-CT investigation of the endocranial morphology of Plesiadapis tricuspidens from the Late Palaeocene of Europe--the most complete plesiadapoid cranium known--shows that plesiadapoids retained a very small and simple brain. Plesiadapis has midbrain exposure, and minimal encephalization and neocorticalization, making it comparable with that of stem rodents and lagomorphs. However, Plesiadapis shares a domed neocortex and downwardly shifted olfactory-bulb axis with Euprimates. If accepted phylogenetic relationships are correct, then this implies that the euprimate brain underwent drastic reorganization during the Palaeocene, and some changes in brain structure preceded brain size increase and neocortex expansion during evolution of the primate brain.

Socioeconomic Status and Functional Brain Development--Associations in Early Infancy

ERIC Educational Resources Information Center

Tomalski, Przemyslaw; Moore, Derek G.; Ribeiro, Helena; Axelsson, Emma L.; Murphy, Elizabeth; Karmiloff-Smith, Annette; Johnson, Mark H.; Kushnerenko, Elena

2013-01-01

Socioeconomic status (SES) impacts on both structural and functional brain development in childhood, but how early its effects can be demonstrated is unknown. In this study we measured resting baseline EEG activity in the gamma frequency range in awake 6-9-month-olds from areas of East London with high socioeconomic deprivation. Between-subject…

Baseline Brain Activity Predicts Response to Neuromodulatory Pain Treatment

PubMed Central

Jensen, Mark P.; Sherlin, Leslie H.; Fregni, Felipe; Gianas, Ann; Howe, Jon D.; Hakimian, Shahin

2015-01-01

Objectives The objective of this study was to examine the associations between baseline electroencephalogram (EEG)-assessed brain oscillations and subsequent response to four neuromodulatory treatments. Based on available research, we hypothesized that baseline theta oscillations would prospectively predict response to hypnotic analgesia. Analyses involving other oscillations and the other treatments (meditation, neurofeedback, and both active and sham transcranial direct current stimulation) were viewed as exploratory, given the lack of previous research examining brain oscillations as predictors of response to these other treatments. Design Randomized controlled study of single sessions of four neuromodulatory pain treatments and a control procedure. Methods Thirty individuals with spinal cord injury and chronic pain had their EEG recorded before each session of four active treatments (hypnosis, meditation, EEG biofeedback, transcranial direct current stimulation) and a control procedure (sham transcranial direct stimulation). Results As hypothesized, more presession theta power was associated with greater response to hypnotic analgesia. In exploratory analyses, we found that less baseline alpha power predicted pain reduction with meditation. Conclusions The findings support the idea that different patients respond to different pain treatments and that between-person treatment response differences are related to brain states as measured by EEG. The results have implications for the possibility of enhancing pain treatment response by either 1) better patient/treatment matching or 2) influencing brain activity before treatment is initiated in order to prepare patients to respond. Research is needed to replicate and confirm the findings in additional samples of individuals with chronic pain. PMID:25287554

Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

PubMed Central

Kleinridders, André; Ferris, Heather A.; Cai, Weikang

2014-01-01

Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. PMID:24931034

Neural Basis of Brain Dysfunction Produced by Early Sleep Problems.

PubMed

Kohyama, Jun

2016-01-29

There is a wealth of evidence that disrupted sleep and circadian rhythms, which are common in modern society even during the early stages of life, have unfavorable effects on brain function. Altered brain function can cause problem behaviors later in life, such as truancy from or dropping out of school, quitting employment, and committing suicide. In this review, we discuss findings from several large cohort studies together with recent results of a cohort study using the marshmallow test, which was first introduced in the 1960s. This test assessed the ability of four-year-olds to delay gratification and showed how this ability correlated with success later in life. The role of the serotonergic system in sleep and how this role changes with age are also discussed. The serotonergic system is involved in reward processing and interactions with the dorsal striatum, ventral striatum, and the prefrontal cortex are thought to comprise the neural basis for behavioral patterns that are affected by the quantity, quality, and timing of sleep early in life.

Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents.

PubMed

Jastreboff, Ania M; Sinha, Rajita; Arora, Jagriti; Giannini, Cosimo; Kubat, Jessica; Malik, Saima; Van Name, Michelle A; Santoro, Nicola; Savoye, Mary; Duran, Elvira J; Pierpont, Bridget; Cline, Gary; Constable, R Todd; Sherwin, Robert S; Caprio, Sonia

2016-07-01

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Planarian shows decision-making behavior in response to multiple stimuli by integrative brain function.

PubMed

Inoue, Takeshi; Hoshino, Hajime; Yamashita, Taiga; Shimoyama, Seira; Agata, Kiyokazu

2015-01-01

Planarians belong to an evolutionarily early group of organisms that possess a central nervous system including a well-organized brain with a simple architecture but many types of neurons. Planarians display a number of behaviors, such as phototaxis and thermotaxis, in response to external stimuli, and it has been shown that various molecules and neural pathways in the brain are involved in controlling these behaviors. However, due to the lack of combinatorial assay methods, it remains obscure whether planarians possess higher brain functions, including integration in the brain, in which multiple signals coming from outside are coordinated and used in determining behavioral strategies. In the present study, we designed chemotaxis and thigmotaxis/kinesis tracking assays to measure several planarian behaviors in addition to those measured by phototaxis and thermotaxis assays previously established by our group, and used these tests to analyze planarian chemotactic and thigmotactic/kinetic behaviors. We found that headless planarian body fragments and planarians that had specifically lost neural activity following regeneration-dependent conditional gene knockdown (Readyknock) of synaptotagmin in the brain lost both chemotactic and thigmotactic behaviors, suggesting that neural activity in the brain is required for the planarian's chemotactic and thigmotactic behaviors. Furthermore, we compared the strength of phototaxis, chemotaxis, thigmotaxis/kinesis, and thermotaxis by presenting simultaneous binary stimuli to planarians. We found that planarians showed a clear order of predominance of these behaviors. For example, when planarians were simultaneously exposed to 400 lux of light and a chemoattractant, they showed chemoattractive behavior irrespective of the direction of the light source, although exposure to light of this intensity alone induces evasive behavior away from the light source. In contrast, when the light intensity was increased to 800 or 1600 lux and

Gut dysbiosis and neuroimmune responses to brain infection with Theiler’s murine encephalomyelitis virus

PubMed Central

Carrillo-Salinas, F. J.; Mestre, L.; Mecha, M.; Feliú, A.; del Campo, R.; Villarrubia, N.; Espejo, C.; Montalbán, X.; Álvarez-Cermeño, J. C.; Villar, L. M.; Guaza, C.

2017-01-01

Recent studies have begun to point out the contribution of microbiota to multiple sclerosis (MS) pathogenesis. Theiler’s murine encephalomyelitis virus induced demyelinating disease (TMEV-IDD) is a model of progressive MS. Here, we first analyze the effect of intracerebral infection with TMEV on commensal microbiota and secondly, whether the early microbiota depletion influences the immune responses to TMEV on the acute phase (14 dpi) and its impact on the chronic phase (85 dpi). The intracranial inoculation of TMEV was associated with a moderate dysbiosis. The oral administration of antibiotics (ABX) of broad spectrum modified neuroimmune responses to TMEV dampening brain CD4+ and CD8+ T infiltration during the acute phase. The expression of cytokines, chemokines and VP2 capsid protein was enhanced and accompanied by clusters of activated microglia disseminated throughout the brain. Furthermore, ABX treated mice displayed lower levels of CD4+ and CD8+T cells in cervical and mesenteric lymph nodes. Increased mortality to TMEV was observed after ABX cessation at day 28pi. On the chronic phase, mice that survived after ABX withdrawal and recovered microbiota diversity showed subtle changes in brain cell infiltrates, microglia and gene expression of cytokines. Accordingly, the surviving mice of the group ABX-TMEV displayed similar disease severity than TMEV mice. PMID:28290524

Early event-related brain potentials that reflect interest for content information in the media.

PubMed

Adachi, Shinobu; Morikawa, Koji; Nittono, Hiroshi

2012-03-28

This study investigated the relationship between event-related brain potentials (ERPs) to abridged content information in the media and the subsequent decisions to view the full content. Student volunteers participated in a task that simulated information selection on the basis of the content information. Screenshots of television clips and headlines of news articles on the Web were used as content information for the image condition and the headline condition, respectively. Following presentation of a stimulus containing content information, participants decided whether or not they would view the full content by pressing a select or a reject button. When the select button was pressed, participants were presented with a television clip or a news article. When the reject button was pressed, participants continued on to the next trial, without viewing further. In comparison with rejected stimuli, selected stimuli elicited a larger negative component, with a peak latency of ∼250 ms. The increase in the negative component was independent of the type of visual stimulus. These results suggest that interest toward content information is reflected in early-stage event-related brain potential responses.

Early disrupted neurovascular coupling and changed event level hemodynamic response function in type 2 diabetes: an fMRI study.

PubMed

Duarte, João V; Pereira, João M S; Quendera, Bruno; Raimundo, Miguel; Moreno, Carolina; Gomes, Leonor; Carrilho, Francisco; Castelo-Branco, Miguel

2015-10-01

Type 2 diabetes (T2DM) patients develop vascular complications and have increased risk for neurophysiological impairment. Vascular pathophysiology may alter the blood flow regulation in cerebral microvasculature, affecting neurovascular coupling. Reduced fMRI signal can result from decreased neuronal activation or disrupted neurovascular coupling. The uncertainty about pathophysiological mechanisms (neurodegenerative, vascular, or both) underlying brain function impairments remains. In this cross-sectional study, we investigated if the hemodynamic response function (HRF) in lesion-free brains of patients is altered by measuring BOLD (Blood Oxygenation Level-Dependent) response to visual motion stimuli. We used a standard block design to examine the BOLD response and an event-related deconvolution approach. Importantly, the latter allowed for the first time to directly extract the true shape of HRF without any assumption and probe neurovascular coupling, using performance-matched stimuli. We discovered a change in HRF in early stages of diabetes. T2DM patients show significantly different fMRI response profiles. Our visual paradigm therefore demonstrated impaired neurovascular coupling in intact brain tissue. This implies that functional studies in T2DM require the definition of HRF, only achievable with deconvolution in event-related experiments. Further investigation of the mechanisms underlying impaired neurovascular coupling is needed to understand and potentially prevent the progression of brain function decrements in diabetes.

Differential effects of voluntary and forced exercise on stress responses after traumatic brain injury.

PubMed

Griesbach, Grace S; Tio, Delia L; Vincelli, Jennifer; McArthur, David L; Taylor, Anna N

2012-05-01

Voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF) after traumatic brain injury (TBI) when it occurs during a delayed time window. In contrast, acute post-TBI exercise does not increase BDNF. It is well known that increases in glucocorticoids suppress levels of BDNF. Moreover, recent work from our laboratory showed that there is a heightened stress response after fluid percussion injury (FPI). In order to determine if a heightened stress response is also observed with acute exercise, at post-injury days 0-4 and 7-11, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) release were measured in rats running voluntarily or exposed to two daily 20-min periods of forced running wheel exercise. Forced, but not voluntary exercise, continuously elevated CORT. ACTH levels were initially elevated with forced exercise, but decreased by post-injury day 7 in the control, but not the FPI animals. As previously reported, voluntary exercise did not increase BDNF in the FPI group as it did in the control animals. Forced exercise did not increase levels of BDNF in any group. It did, however, decrease hippocampal glucocorticoid receptors in the control group. The results suggest that exercise regimens with strong stress responses may not be beneficial during the early post-injury period.

R6/2 Huntington's disease mice develop early and progressive abnormal brain metabolism and seizures.

PubMed

Cepeda-Prado, Efrain; Popp, Susanna; Khan, Usman; Stefanov, Dimitre; Rodríguez, Jorge; Menalled, Liliana B; Dow-Edwards, Diana; Small, Scott A; Moreno, Herman

2012-05-09

A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [(14)C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An interesting mismatch between increases in rCBV and decreases in glucose uptake was observed. Finally, we evaluated the sensitivity of this mouse line to audiogenic seizures early in the disease course. We found that R6/2 mice had an increased susceptibility to develop seizures. Together, these findings identified seizure activity in R6/2 mice and show that neuroimaging measures sensitive to oxygen metabolism can be used as in vivo biomarkers, preceding the onset of an overt behavioral phenotype. Since fMRI-rCBV can also be obtained in patients, we propose that it may serve as a translational tool to evaluate therapeutic responses in humans and HD mouse models.

Fuel not fun: Reinterpreting attenuated brain responses to reward in obesity.

PubMed

Kroemer, Nils B; Small, Dana M

2016-08-01

There is a well-established literature linking obesity to altered dopamine signaling and brain response to food-related stimuli. Neuroimaging studies frequently report enhanced responses in dopaminergic regions during food anticipation and decreased responses during reward receipt. This has been interpreted as reflecting anticipatory "reward surfeit", and consummatory "reward deficiency". In particular, attenuated response in the dorsal striatum to primary food rewards is proposed to reflect anhedonia, which leads to overeating in an attempt to compensate for the reward deficit. In this paper, we propose an alternative view. We consider brain response to food-related stimuli in a reinforcement-learning framework, which can be employed to separate the contributions of reward sensitivity and reward-related learning that are typically entangled in the brain response to reward. Consequently, we posit that decreased striatal responses to milkshake receipt reflect reduced reward-related learning rather than reward deficiency or anhedonia because reduced reward sensitivity would translate uniformly into reduced anticipatory and consummatory responses to reward. By re-conceptualizing reward deficiency as a shift in learning about subjective value of rewards, we attempt to reconcile neuroimaging findings with the putative role of dopamine in effort, energy expenditure and exploration and suggest that attenuated brain responses to energy dense foods reflect the "fuel", not the fun entailed by the reward. Copyright © 2016 Elsevier Inc. All rights reserved.

[Early mobilization. Competencies, responsibilities, milestones].

PubMed

Nydahl, P; Dewes, M; Dubb, R; Filipovic, S; Hermes, C; Jüttner, F; Kaltwasser, A; Klarmann, S; Klas, K; Mende, H; Rothaug, O; Schuchhardt, D

2016-03-01

Early mobilization is an evident, interprofessional concept to improve the outcome of intensive care patients. It reduces psychocognitive deficits and delirium and attenuates a general deconditioning, including atrophy of the respiratory pump and skeletal muscles. In this regard the interdisciplinary approach of early mobilization, taking into account different levels of mobilization, appears to be beneficial. The purpose of this study was to explore opinions on collaboration and tasks between different professional groups. During the 25th Bremen Conference on Intensive Medicine and Nursing on 20 February 2015, a questionnaire survey was carried out among the 120 participants of the German Early Mobilization Network meeting. In all, 102 questionnaires were analyzed. Most participants reported on the interdisciplinarity of the approach, but none of the tasks and responsibilities concerning early mobilization can be assigned to a single professional group. The practical implementation of mobilizing orally intubated patients may require two registered nurses as well as a physical therapist. Implementation in daily practice seems to be heterogeneous. There is no consensus regarding collaboration, competencies, and responsibilities with respect to early mobilization of intensive care patients. The approach to date has been characterized by a lack of interprofessional communication, which may lead to an inefficient use of the broad and varied base of knowledge and experienceof the different professions.

Atypical temporal activation pattern and central-right brain compensation during semantic judgment task in children with early left brain damage.

PubMed

Chang, Yi-Tzu; Lin, Shih-Che; Meng, Ling-Fu; Fan, Yang-Teng

In this study we investigated the event-related potentials (ERPs) during the semantic judgment task (deciding if the two Chinese characters were semantically related or unrelated) to identify the timing of neural activation in children with early left brain damage (ELBD). The results demonstrated that compared with the controls, children with ELBD had (1) competitive accuracy and reaction time in the semantic judgment task, (2) weak operation of the N400, (3) stronger, earlier and later compensational positivities (referred to the enhanced P200, P250, and P600 amplitudes) in the central and right region of the brain to successfully engage in semantic judgment. Our preliminary findings indicate that temporally postlesional reorganization is in accordance with the proposed right-hemispheric organization of speech after early left-sided brain lesion. During semantic processing, the orthography has a greater effect on the children with ELBD, and a later semantic reanalysis (P600) is required due to the less efficient N400 at the former stage for semantic integration. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of Early Adversity and Childhood Internalizing Symptoms on Brain Structure in Young Men.

PubMed

Jensen, Sarah K G; Dickie, Erin W; Schwartz, Deborah H; Evans, C John; Dumontheil, Iroise; Paus, Tomáš; Barker, Edward D

2015-10-01

Early adversity is an important risk factor that relates to internalizing symptoms and altered brain structure. To assess the direct effects of early adversity and child internalizing symptoms (ie, depression, anxiety) on cortical gray matter (GM) volume, as well as the extent to which early adversity associates with variation in cortical GM volume indirectly via increased levels of internalizing symptoms. A prospective investigation of associations between adversity within the first 6 years of life, internalizing symptoms during childhood and early adolescence, and altered brain structure in late adolescence (age, 18-21 years) was conducted in a community-based birth cohort in England (Avon Longitudinal Study of Parents and Children). Participants from the cohort included 494 mother-son pairs monitored since the mothers were pregnant (estimated date of delivery between April 1, 1991, and December 31, 1992). Data collection for the present study was conducted between April 1, 1991, and November 30, 2010; the neuroimaging data were collected between September 1, 2010, and November 30, 2012, and data analyses for the present study occurred between January 25, 2013, and February 15, 2015. Risk factors were adversity within the first 6 years of the child's life (including prenatal exposure) and the child's internalizing symptoms between age 7 and 13 years. Early childhood adversity. The main outcome was GM volume of cortical regions previously associated with major depression measured through T1-weighted magnetic resonance images collected in late adolescence. Among 494 young men included in this analysis, early adversity was directly associated with lower GM volumes in the anterior cingulate cortex (β = -.18; P = .01) and higher GM volume in the precuneus (β = .18; P = .009). Childhood internalizing symptoms were associated with lower GM volume in the right superior frontal gyrus (β = -.20; P = .002). Early adversity was also associated with higher

The brain responses to different frequencies of binaural beat sounds on QEEG at cortical level.

PubMed

Jirakittayakorn, Nantawachara; Wongsawat, Yodchanan

2015-01-01

Beat phenomenon is occurred when two slightly different frequency waves interfere each other. The beat can also occur in the brain by providing two slightly different frequency waves separately each ear. This is called binaural beat. The brain responses to binaural beat are in discussion process whether the brain side and the brain area. Therefore, this study aims to figure out the brain responses to binaural beat by providing different binaural beat frequencies on 250 carrier tone continuously for 30 minutes to participants and using quantitative electroencephalography (QEEG) to interpret the data. The result shows that different responses appear in different beat frequency. Left hemisphere dominance occur in 3 Hz beat within 15 minutes and 15 Hz beat within 5 minutes. Right hemisphere dominance occurs in 10 Hz beat within 25 minute. 6 Hz beat enhances all area of the brain within 10 minutes. 8 Hz and 25 Hz beats have no clearly responses while 40 Hz beat enhances the responses in frontal lobe. These brain responses can be used for brain modulation application to induce the brain activity in further studies.

Investigating Neuromagnetic Brain Responses against Chromatic Flickering Stimuli by Wavelet Entropies

PubMed Central

Bhagat, Mayank; Bhushan, Chitresh; Saha, Goutam; Shimjo, Shinsuke; Watanabe, Katsumi; Bhattacharya, Joydeep

2009-01-01

Background Photosensitive epilepsy is a type of reflexive epilepsy triggered by various visual stimuli including colourful ones. Despite the ubiquitous presence of colorful displays, brain responses against different colour combinations are not properly studied. Methodology/Principal Findings Here, we studied the photosensitivity of the human brain against three types of chromatic flickering stimuli by recording neuromagnetic brain responses (magnetoencephalogram, MEG) from nine adult controls, an unmedicated patient, a medicated patient, and two controls age-matched with patients. Dynamical complexities of MEG signals were investigated by a family of wavelet entropies. Wavelet entropy is a newly proposed measure to characterize large scale brain responses, which quantifies the degree of order/disorder associated with a multi-frequency signal response. In particular, we found that as compared to the unmedicated patient, controls showed significantly larger wavelet entropy values. We also found that Renyi entropy is the most powerful feature for the participant classification. Finally, we also demonstrated the effect of combinational chromatic sensitivity on the underlying order/disorder in MEG signals. Conclusions/Significance Our results suggest that when perturbed by potentially epileptic-triggering stimulus, healthy human brain manages to maintain a non-deterministic, possibly nonlinear state, with high degree of disorder, but an epileptic brain represents a highly ordered state which making it prone to hyper-excitation. Further, certain colour combination was found to be more threatening than other combinations. PMID:19779630

Investigating neuromagnetic brain responses against chromatic flickering stimuli by wavelet entropies.

PubMed

Bhagat, Mayank; Bhushan, Chitresh; Saha, Goutam; Shimjo, Shinsuke; Watanabe, Katsumi; Bhattacharya, Joydeep

2009-09-25

Photosensitive epilepsy is a type of reflexive epilepsy triggered by various visual stimuli including colourful ones. Despite the ubiquitous presence of colorful displays, brain responses against different colour combinations are not properly studied. Here, we studied the photosensitivity of the human brain against three types of chromatic flickering stimuli by recording neuromagnetic brain responses (magnetoencephalogram, MEG) from nine adult controls, an unmedicated patient, a medicated patient, and two controls age-matched with patients. Dynamical complexities of MEG signals were investigated by a family of wavelet entropies. Wavelet entropy is a newly proposed measure to characterize large scale brain responses, which quantifies the degree of order/disorder associated with a multi-frequency signal response. In particular, we found that as compared to the unmedicated patient, controls showed significantly larger wavelet entropy values. We also found that Renyi entropy is the most powerful feature for the participant classification. Finally, we also demonstrated the effect of combinational chromatic sensitivity on the underlying order/disorder in MEG signals. Our results suggest that when perturbed by potentially epileptic-triggering stimulus, healthy human brain manages to maintain a non-deterministic, possibly nonlinear state, with high degree of disorder, but an epileptic brain represents a highly ordered state which making it prone to hyper-excitation. Further, certain colour combination was found to be more threatening than other combinations.

From Whole-Brain Data to Functional Circuit Models: The Zebrafish Optomotor Response.

PubMed

Naumann, Eva A; Fitzgerald, James E; Dunn, Timothy W; Rihel, Jason; Sompolinsky, Haim; Engert, Florian

2016-11-03

Detailed descriptions of brain-scale sensorimotor circuits underlying vertebrate behavior remain elusive. Recent advances in zebrafish neuroscience offer new opportunities to dissect such circuits via whole-brain imaging, behavioral analysis, functional perturbations, and network modeling. Here, we harness these tools to generate a brain-scale circuit model of the optomotor response, an orienting behavior evoked by visual motion. We show that such motion is processed by diverse neural response types distributed across multiple brain regions. To transform sensory input into action, these regions sequentially integrate eye- and direction-specific sensory streams, refine representations via interhemispheric inhibition, and demix locomotor instructions to independently drive turning and forward swimming. While experiments revealed many neural response types throughout the brain, modeling identified the dimensions of functional connectivity most critical for the behavior. We thus reveal how distributed neurons collaborate to generate behavior and illustrate a paradigm for distilling functional circuit models from whole-brain data. Copyright © 2016 Elsevier Inc. All rights reserved.

Culture and the Brain: Making the Most of Learning in the Early Childhood Classroom

ERIC Educational Resources Information Center

Thomas-Fair, Ursula

2007-01-01

This article reviews the impetus for higher quality, culturally appropriate early learning experiences. It investigates the economic costs of low quality learning and the absence of early learning programs as well. The article identifies and explores the tenets of brain-based learning and its connection to culture. Finally, the article describes…

Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

NASA Astrophysics Data System (ADS)

Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

1998-12-01

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

Brain Responses Differ to Faces of Mothers and Fathers

ERIC Educational Resources Information Center

Arsalidou, Marie; Barbeau, Emmanuel J.; Bayless, Sarah J.; Taylor, Margot J.

2010-01-01

We encounter many faces each day but relatively few are personally familiar. Once faces are familiar, they evoke semantic and social information known about the person. Neuroimaging studies demonstrate differential brain activity to familiar and non-familiar faces; however, brain responses related to personally familiar faces have been more rarely…

Activation of bradykinin B2 receptor induced the inflammatory responses of cytosolic phospholipase A2 after the early traumatic brain injury.

PubMed

Chao, Honglu; Liu, Yinlong; Lin, Chao; Xu, Xiupeng; Li, Zheng; Bao, Zhongyuan; Fan, Liang; Tao, Chao; Zhao, Lin; Liu, Yan; Wang, Xiaoming; You, Yongping; Liu, Ning; Ji, Jing

2018-06-09

Phospholipase A 2 is a known aggravator of inflammation and deteriorates neurological outcomes after traumatic brain injury (TBI), however the exact inflammatory mechanisms remain unknown. This study investigated the role of bradykinin and its receptor, which are known initial mediators within inflammation activation, as well as the mechanisms of the cytosolic phospholipase A 2 (cPLA 2 )-related inflammatory responses after TBI. We found that cPLA 2 and bradykinin B2 receptor were upregulated after a TBI. Rats treated with the bradykinin B2 receptor inhibitor LF 16-0687 exhibited significantly less cPLA 2 expression and related inflammatory responses in the brain cortex after sustaining a controlled cortical impact (CCI) injury. Both the cPLA 2 inhibitor and the LF16-0687 improved CCI rat outcomes by decreasing neuron death and reducing brain edema. The following TBI model utilized both primary astrocytes and primary neurons in order to gain further understanding of the inflammation mechanisms of the B2 bradykinin receptor and the cPLA 2 in the central nervous system. There was a stronger reaction from the astrocytes as well as a protective effect of LF16-0687 after the stretch injury and bradykinin treatment. The protein kinase C pathway was thought to be involved in the B2 bradykinin receptor as well as the cPLA 2 -related inflammatory responses. Rottlerin, a Protein Kinase C (PKC) δ inhibitor, decreased the activity of the cPLA 2 activity post-injury, and LF16-0687 suppressed both the PKC pathway and the cPLA 2 activity within the astrocytes. These results indicated that the bradykinin B2 receptor-mediated pathway is involved in the cPLA 2 -related inflammatory response from the PKC pathway. Copyright © 2018. Published by Elsevier B.V.

Impact of Blood-Brain Barrier Integrity on Tumor Growth and Therapy Response in Brain Metastases.

PubMed

Osswald, Matthias; Blaes, Jonas; Liao, Yunxiang; Solecki, Gergely; Gömmel, Miriam; Berghoff, Anna S; Salphati, Laurent; Wallin, Jeffrey J; Phillips, Heidi S; Wick, Wolfgang; Winkler, Frank

2016-12-15

The role of blood-brain barrier (BBB) integrity for brain tumor biology and therapy is a matter of debate. We developed a new experimental approach using in vivo two-photon imaging of mouse brain metastases originating from a melanoma cell line to investigate the growth kinetics of individual tumor cells in response to systemic delivery of two PI3K/mTOR inhibitors over time, and to study the impact of microregional vascular permeability. The two drugs are closely related but differ regarding a minor chemical modification that greatly increases brain penetration of one drug. Both inhibitors demonstrated a comparable inhibition of downstream targets and melanoma growth in vitro In vivo, increased BBB permeability to sodium fluorescein was associated with accelerated growth of individual brain metastases. Melanoma metastases with permeable microvessels responded similarly to equivalent doses of both inhibitors. In contrast, metastases with an intact BBB showed an exclusive response to the brain-penetrating inhibitor. The latter was true for macro- and micrometastases, and even single dormant melanoma cells. Nuclear morphology changes and single-cell regression patterns implied that both inhibitors, if extravasated, target not only perivascular melanoma cells but also those distant to blood vessels. Our study provides the first direct evidence that nonpermeable brain micro- and macrometastases can effectively be targeted by a drug designed to cross the BBB. Small-molecule inhibitors with these optimized properties are promising agents in preventing or treating brain metastases in patients. Clin Cancer Res; 22(24); 6078-87. ©2016 AACRSee related commentary by Steeg et al., p. 5953. ©2016 American Association for Cancer Research.

Pre-pubertal stress exposure affects adult behavioral response in association with changes in circulating corticosterone and brain-derived neurotrophic factor.

PubMed

Bazak, Noam; Kozlovsky, Nitsan; Kaplan, Zeev; Matar, Michael; Golan, Hava; Zohar, Joseph; Richter-Levin, Gal; Cohen, Hagit

2009-07-01

Early-life stress produces a cascade of neurobiological events that cause enduring changes in neural plasticity and synaptic efficacy that appear to play pivotal roles in the pathophysiology of post-traumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) has been implicated in the neurobiological mechanisms of these changes, in interaction with components of the stress response, such as corticosterone. This study examined the consequences of juvenile stress for behavior during adulthood in association with circulating corticosterone levels and BDNF expression. The experiments examined single exposure to predator scent stress (soiled cat litter for 10 min) as compared to repeated exposure, early in life and later on. Behavioral responses were assessed in the elevated plus maze and the acoustic startle response paradigms at 28, 60 and 90 days of age. Plasma corticosterone was measured and brain areas analyzed for BDNF levels. The results show that juvenile stress exposure increased anxiety-like behavior and startle amplitude and decreased plasma corticosterone. This response was seen immediately after exposure and also long term. Adult stress exposure increased anxiety-like behavior, startle amplitude and plasma corticosterone. Exposure to both early and later life trauma elicited reduced levels of corticosterone following the initial exposure, which were not raised by re-exposure, and elicited significant downregulation of BDNF mRNA and protein levels in the hippocampus CA1 subregion. The consequences of adult stress exposure were more severe in rats were exposed to the same stressor as juveniles, indicated increased vulnerability. The results suggest that juvenile stress has resounding effects in adulthood reflected in behavioral responses. The concomitant changes in BDNF and corticosterone levels may mediate the changes in neural plasticity and synaptic functioning underlying clinical manifestations of PTSD.

Multiscale energy reallocation during low-frequency steady-state brain response.

PubMed

Wang, Yifeng; Chen, Wang; Ye, Liangkai; Biswal, Bharat B; Yang, Xuezhi; Zou, Qijun; Yang, Pu; Yang, Qi; Wang, Xinqi; Cui, Qian; Duan, Xujun; Liao, Wei; Chen, Huafu

2018-05-01

Traditional task-evoked brain activations are based on detection and estimation of signal change from the mean signal. By contrast, the low-frequency steady-state brain response (lfSSBR) reflects frequency-tagging activity at the fundamental frequency of the task presentation and its harmonics. Compared to the activity at these resonant frequencies, brain responses at nonresonant frequencies are largely unknown. Additionally, because the lfSSBR is defined by power change, we hypothesize using Parseval's theorem that the power change reflects brain signal variability rather than the change of mean signal. Using a face recognition task, we observed power increase at the fundamental frequency (0.05 Hz) and two harmonics (0.1 and 0.15 Hz) and power decrease within the infra-slow frequency band (<0.1 Hz), suggesting a multifrequency energy reallocation. The consistency of power and variability was demonstrated by the high correlation (r > .955) of their spatial distribution and brain-behavior relationship at all frequency bands. Additionally, the reallocation of finite energy was observed across various brain regions and frequency bands, forming a particular spatiotemporal pattern. Overall, results from this study strongly suggest that frequency-specific power and variability may measure the same underlying brain activity and that these results may shed light on different mechanisms between lfSSBR and brain activation, and spatiotemporal characteristics of energy reallocation induced by cognitive tasks. © 2018 Wiley Periodicals, Inc.

How the Timing and Quality of Early Experiences Influence the Development of Brain Architecture

ERIC Educational Resources Information Center

Fox, Sharon E.; Levitt, Pat; Nelson, Charles A., III.

2010-01-01

Early life events can exert a powerful influence on both the pattern of brain architecture and behavioral development. In this study a conceptual framework is provided for considering how the structure of early experience gets "under the skin." The study begins with a description of the genetic framework that lays the foundation for brain…

Effects of Experience on the Brain: The Role of Neuroscience in Early Development and Education

ERIC Educational Resources Information Center

Twardosz, Sandra

2012-01-01

Research Findings: Research on the effect of experience on the structure and function of the brain across the lifespan pertains directly to the concerns of professionals involved with children's early development and education. This paper briefly reviews (a) the role of experience in shaping the developing brain, (b) individual adaptation to the…

Transcriptional regulation of brain gene expression in response to a territorial intrusion

PubMed Central

Sanogo, Yibayiri O.; Band, Mark; Blatti, Charles; Sinha, Saurabh; Bell, Alison M.

2012-01-01

Aggressive behaviour associated with territorial defence is widespread and has fitness consequences. However, excess aggression can interfere with other important biological functions such as immunity and energy homeostasis. How the expression of complex behaviours such as aggression is regulated in the brain has long intrigued ethologists, but has only recently become amenable for molecular dissection in non-model organisms. We investigated the transcriptomic response to territorial intrusion in four brain regions in breeding male threespined sticklebacks using expression microarrays and quantitative polymerase chain reaction (qPCR). Each region of the brain had a distinct genomic response to a territorial challenge. We identified a set of genes that were upregulated in the diencephalon and downregulated in the cerebellum and the brain stem. Cis-regulatory network analysis suggested transcription factors that regulated or co-regulated genes that were consistently regulated in all brain regions and others that regulated gene expression in opposing directions across brain regions. Our results support the hypothesis that territorial animals respond to social challenges via transcriptional regulation of genes in different brain regions. Finally, we found a remarkably close association between gene expression and aggressive behaviour at the individual level. This study sheds light on the molecular mechanisms in the brain that underlie the response to social challenges. PMID:23097509

More insights into early brain development through statistical analyses of eigen-structural elements of diffusion tensor imaging using multivariate adaptive regression splines

PubMed Central

Chen, Yasheng; Zhu, Hongtu; An, Hongyu; Armao, Diane; Shen, Dinggang; Gilmore, John H.; Lin, Weili

2013-01-01

The aim of this study was to characterize the maturational changes of the three eigenvalues (λ1 ≥ λ2 ≥ λ3) of diffusion tensor imaging (DTI) during early postnatal life for more insights into early brain development. In order to overcome the limitations of using presumed growth trajectories for regression analysis, we employed Multivariate Adaptive Regression Splines (MARS) to derive data-driven growth trajectories for the three eigenvalues. We further employed Generalized Estimating Equations (GEE) to carry out statistical inferences on the growth trajectories obtained with MARS. With a total of 71 longitudinal datasets acquired from 29 healthy, full-term pediatric subjects, we found that the growth velocities of the three eigenvalues were highly correlated, but significantly different from each other. This paradox suggested the existence of mechanisms coordinating the maturations of the three eigenvalues even though different physiological origins may be responsible for their temporal evolutions. Furthermore, our results revealed the limitations of using the average of λ2 and λ3 as the radial diffusivity in interpreting DTI findings during early brain development because these two eigenvalues had significantly different growth velocities even in central white matter. In addition, based upon the three eigenvalues, we have documented the growth trajectory differences between central and peripheral white matter, between anterior and posterior limbs of internal capsule, and between inferior and superior longitudinal fasciculus. Taken together, we have demonstrated that more insights into early brain maturation can be gained through analyzing eigen-structural elements of DTI. PMID:23455648

Statistical process control: A feasibility study of the application of time-series measurement in early neurorehabilitation after acquired brain injury.

PubMed

Markovic, Gabriela; Schult, Marie-Louise; Bartfai, Aniko; Elg, Mattias

2017-01-31

Progress in early cognitive recovery after acquired brain injury is uneven and unpredictable, and thus the evaluation of rehabilitation is complex. The use of time-series measurements is susceptible to statistical change due to process variation. To evaluate the feasibility of using a time-series method, statistical process control, in early cognitive rehabilitation. Participants were 27 patients with acquired brain injury undergoing interdisciplinary rehabilitation of attention within 4 months post-injury. The outcome measure, the Paced Auditory Serial Addition Test, was analysed using statistical process control. Statistical process control identifies if and when change occurs in the process according to 3 patterns: rapid, steady or stationary performers. The statistical process control method was adjusted, in terms of constructing the baseline and the total number of measurement points, in order to measure a process in change. Statistical process control methodology is feasible for use in early cognitive rehabilitation, since it provides information about change in a process, thus enabling adjustment of the individual treatment response. Together with the results indicating discernible subgroups that respond differently to rehabilitation, statistical process control could be a valid tool in clinical decision-making. This study is a starting-point in understanding the rehabilitation process using a real-time-measurements approach.

Influence of strain rate on indentation response of porcine brain.

PubMed

Qian, Long; Zhao, Hongwei; Guo, Yue; Li, Yuanshang; Zhou, Mingxing; Yang, Liguo; Wang, Zhiwei; Sun, Yifan

2018-06-01

Knowledge of brain tissue mechanical properties may be critical for formulating hypotheses about some specific diseases mechanisms and its accurate simulations such as traumatic brain injury (TBI) and tumor growth. Compared to traditional tests (e.g. tensile and compression), indentation shows superiority by virtue of its pinpoint and nondestructive/quasi-nondestructive. As a viscoelastic material, the properties of brain tissue depend on the strain rate by definition. However most efforts focus on the aspect of velocity in the field of brain indentation, rather than strain rate. The influence of strain rate on indentation response of brain tissue is taken little attention. Further, by comparing different results from literatures, it is also obvious that strain rate rather than velocity is more appropriate to characterize mechanical properties of brain. In this paper, to systematically characterize the influence of strain rate, a series of indentation-relaxation tests n = 210) are performed on the cortex of porcine brain using a custom-designed indentation device. The mechanical response that correlates with indenter diameters, depths of indentation and velocities, is revealed for the indentation portion, and elastic behavior of brain tissue is analyzed as the function of strain rate. Similarly, a linear viscoelastic model with a Prony series is employed for the indentation-relaxation portion, wherein the brain tissue shows more viscous and responds more quickly with increasing strain rate. Understanding the effect of strain rate on mechanical properties of brain indentation may be far-reaching for brain injury biomechanics and accurate simulations, but be important for bridging between indentation results of different literatures. Copyright © 2018 Elsevier Ltd. All rights reserved.

Inducing task-relevant responses to speech in the sleeping brain.

PubMed

Kouider, Sid; Andrillon, Thomas; Barbosa, Leonardo S; Goupil, Louise; Bekinschtein, Tristan A

2014-09-22

Falling asleep leads to a loss of sensory awareness and to the inability to interact with the environment [1]. While this was traditionally thought as a consequence of the brain shutting down to external inputs, it is now acknowledged that incoming stimuli can still be processed, at least to some extent, during sleep [2]. For instance, sleeping participants can create novel sensory associations between tones and odors [3] or reactivate existing semantic associations, as evidenced by event-related potentials [4-7]. Yet, the extent to which the brain continues to process external stimuli remains largely unknown. In particular, it remains unclear whether sensory information can be processed in a flexible and task-dependent manner by the sleeping brain, all the way up to the preparation of relevant actions. Here, using semantic categorization and lexical decision tasks, we studied task-relevant responses triggered by spoken stimuli in the sleeping brain. Awake participants classified words as either animals or objects (experiment 1) or as either words or pseudowords (experiment 2) by pressing a button with their right or left hand, while transitioning toward sleep. The lateralized readiness potential (LRP), an electrophysiological index of response preparation, revealed that task-specific preparatory responses are preserved during sleep. These findings demonstrate that despite the absence of awareness and behavioral responsiveness, sleepers can still extract task-relevant information from external stimuli and covertly prepare for appropriate motor responses. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Na+/H+ Exchanger 9 Regulates Iron Mobilization at the Blood-Brain Barrier in Response to Iron Starvation.

PubMed

Beydoun, Rami; Hamood, Mohamed A; Gomez Zubieta, Daniela M; Kondapalli, Kalyan C

2017-03-10

Iron is essential for brain function, with loss of iron homeostasis in the brain linked to neurological diseases ranging from rare syndromes to more common disorders, such as Parkinson's and Alzheimer's diseases. Iron entry into the brain is regulated by the blood-brain barrier (BBB). Molecular mechanisms regulating this transport are poorly understood. Using an in vitro model of the BBB, we identify NHE9, an endosomal cation/proton exchanger, as a novel regulator of this system. Human brain microvascular endothelial cells (hBMVECs) that constitute the BBB receive brain iron status information via paracrine signals from ensheathing astrocytes. In hBMVECs, we show that NHE9 expression is up-regulated very early in a physiological response invoked by paracrine signals from iron-starved astrocytes. Ectopic expression of NHE9 in hBMVECs without external cues induced up-regulation of the transferrin receptor (TfR) and down-regulation of ferritin, leading to an increase in iron uptake. Mechanistically, we demonstrate that NHE9 localizes to recycling endosomes in hBMVECs where it raises the endosomal pH. The ensuing alkalization of the endosomal lumen increased translocation of TfRs to the hBMVEC membrane. TfRs on the membrane were previously shown to facilitate both recycling-dependent and -independent iron uptake. We propose that NHE9 regulates TfR-dependent, recycling-independent iron uptake in hBMVECs by fine-tuning the endosomal pH in response to paracrine signals and is therefore an important regulator in iron mobilization pathway at the BBB. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Automated brain computed tomographic densitometry of early ischemic changes in acute stroke

PubMed Central

Stoel, Berend C.; Marquering, Henk A.; Staring, Marius; Beenen, Ludo F.; Slump, Cornelis H.; Roos, Yvo B.; Majoie, Charles B.

2015-01-01

Abstract. The Alberta Stroke Program Early CT score (ASPECTS) scoring method is frequently used for quantifying early ischemic changes (EICs) in patients with acute ischemic stroke in clinical studies. Varying interobserver agreement has been reported, however, with limited agreement. Therefore, our goal was to develop and evaluate an automated brain densitometric method. It divides CT scans of the brain into ASPECTS regions using atlas-based segmentation. EICs are quantified by comparing the brain density between contralateral sides. This method was optimized and validated using CT data from 10 and 63 patients, respectively. The automated method was validated against manual ASPECTS, stroke severity at baseline and clinical outcome after 7 to 10 days (NIH Stroke Scale, NIHSS) and 3 months (modified Rankin Scale). Manual and automated ASPECTS showed similar and statistically significant correlations with baseline NIHSS (R=−0.399 and −0.277, respectively) and with follow-up mRS (R=−0.256 and −0.272), except for the follow-up NIHSS. Agreement between automated and consensus ASPECTS reading was similar to the interobserver agreement of manual ASPECTS (differences <1 point in 73% of cases). The automated ASPECTS method could, therefore, be used as a supplementary tool to assist manual scoring. PMID:26158082

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate

PubMed Central

Falcone, Mary; Cao, Wen; Bernardo, Leah; Tyndale, Rachel F; Loughead, James; Lerman, Caryn

2017-01-01

Background Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (NMR, 3′-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance, and a well validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. Methods Sixty-nine treatment-seeking smokers (30 slow, 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once following 24 hours of smoking abstinence. Results In whole brain analysis, normal (compared to slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were even more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. Conclusion Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. PMID:26805583

Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate.

PubMed

Falcone, Mary; Cao, Wen; Bernardo, Leah; Tyndale, Rachel F; Loughead, James; Lerman, Caryn

2016-08-01

Inherited differences in the rate of metabolism of nicotine, the addictive chemical in tobacco, affect smoking behavior and quitting success. The nicotine metabolite ratio (3'-hydroxycotinine/cotinine) is a reliable measure of nicotine clearance and a well-validated predictive biomarker of response to pharmacotherapy. To clarify the mechanisms underlying these associations, we investigated the neural responses to smoking cues in normal and slow nicotine metabolizers. Treatment-seeking smokers (N = 69; 30 slow metabolizers and 39 normal metabolizers) completed a visual cue reactivity task during functional magnetic resonance imaging on two separate occasions: once during smoking satiety and once after 24 hours of smoking abstinence. In whole-brain analysis, normal (compared with slow) metabolizers exhibited heightened abstinence-induced neural responses to smoking cues in the left caudate, left inferior frontal gyrus, and left frontal pole. These effects were more pronounced when extreme groups of slow and normal metabolizers were examined. Greater activation in the left caudate and left frontal pole was associated with abstinence-induced subjective cravings to smoke. Inherited differences in rate of nicotine elimination may drive neural responses to smoking cues during early abstinence, providing a plausible mechanism to explain differences in smoking behaviors and response to cessation treatment. Normal metabolizers may benefit from adjunctive behavioral smoking cessation treatments, such as cue exposure therapy. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Cellular responses to recurrent pentylenetetrazole-induced seizures in the adult zebrafish brain

PubMed Central

Duy, Phan Q; Berberoglu, Michael A; Beattie, Christine E; Hall, Charles W

2017-01-01

A seizure is a sustained increase in brain electrical activity that can result in loss of consciousness and injury. Understanding how the brain responds to seizures is important for development of new treatment strategies for epilepsy, a neurological condition characterized by recurrent and unprovoked seizures. Pharmacological induction of seizures in rodent models results in a myriad of cellular alterations, including inflammation, angiogenesis, and adult neurogenesis. The purpose of this study is to investigate the cellular responses to recurrent pentylenetetrazole seizures in the adult zebrafish brain. We subjected zebrafish to five once daily pentylenetetrazole induced seizures and characterized the cellular consequences of these seizures. In response to recurrent seizures, we found histologic evidence of vasodilatation, perivascular leukocyte egress and leukocyte proliferation suggesting seizure-induced acute CNS inflammation. We also found evidence of increased proliferation, neurogenesis, and reactive gliosis. Collectively, our results suggest that the cellular responses to seizures in the adult zebrafish brain are similar to those observed in mammalian brains. PMID:28238851

Connecting Brian Cambourne's Conditions of Learning Theory to Brain/Mind Principles: Implications for Early Childhood Educators.

ERIC Educational Resources Information Center

Rushton, Stephen P.; Eitelgeorge, Janice; Zickafoose, Ruby

2003-01-01

Relates each of the eight conditions of learning in Brian Cambourne's theory of literacy to findings in brain research within a constructivist approach to early childhood education. Cites sample classroom dialogues demonstrating classroom elements that foster a brain-based, developmentally appropriate learning environment supporting Cambourne's…

Chasing Tics in the Human Brain: Development of Open, Scheduled and Closed Loop Responsive Approaches to Deep Brain Stimulation for Tourette Syndrome

PubMed Central

Martinez-Ramirez, Daniel; Rossi, Peter J.; Peng, Zhongxing; Gunduz, Aysegul; Okun, Michael S.

2015-01-01

Tourette syndrome is a childhood-onset disorder characterized by a combination of motor and vocal tics, often associated with psychiatric comorbidities including attention deficit and hyperactivity disorder and obsessive-compulsive disorder. Despite an onset early in life, half of patients may present symptoms in adulthood, with variable degrees of severity. In select cases, the syndrome may lead to significant physical and social impairment, and a worrisome risk for self injury. Evolving research has provided evidence supporting the idea that the pathophysiology of Tourette syndrome is directly related to a disrupted circuit involving the cortex and subcortical structures, including the basal ganglia, nucleus accumbens, and the amygdala. There has also been a notion that a dysfunctional group of neurons in the putamen contributes to an abnormal facilitation of competing motor responses in basal ganglia structures ultimately underpinning the generation of tics. Surgical therapies for Tourette syndrome have been reserved for a small group of patients not responding to behavioral and pharmacological therapies, and these therapies have been directed at modulating the underlying pathophysiology. Lesion therapy as well as deep brain stimulation has been observed to suppress tics in at least some of these cases. In this article, we will review the clinical aspects of Tourette syndrome, as well as the evolution of surgical approaches and we will discuss the evidence and clinical responses to deep brain stimulation in various brain targets. We will also discuss ongoing research and future directions as well as approaches for open, scheduled and closed loop feedback-driven electrical stimulation for the treatment of Tourette syndrome. PMID:25851890

Decreased prefrontal functional brain response during memory testing in women with Cushing's syndrome in remission.

PubMed

Ragnarsson, Oskar; Stomby, Andreas; Dahlqvist, Per; Evang, Johan A; Ryberg, Mats; Olsson, Tommy; Bollerslev, Jens; Nyberg, Lars; Johannsson, Gudmundur

2017-08-01

Neurocognitive dysfunction is an important feature of Cushing's syndrome (CS). Our hypothesis was that patients with CS in remission have decreased functional brain responses in the prefrontal cortex and hippocampus during memory testing. In this cross-sectional study we included 19 women previously treated for CS and 19 controls matched for age, gender, and education. The median remission time was 7 (IQR 6-10) years. Brain activity was studied with functional magnetic resonance imaging during episodic- and working-memory tasks. The primary regions of interest were the prefrontal cortex and the hippocampus. A voxel-wise comparison of functional brain responses in patients and controls was performed. During episodic-memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (p<0.001) and in the right inferior occipital gyrus (p<0.001) compared with controls. There was a trend towards lower functional brain responses in the left posterior hippocampus in patients (p=0.05). During episodic-memory retrieval, the patients displayed lower functional brain responses in several brain areas with the most predominant difference in the right prefrontal cortex (p<0.001). During the working memory task, patients had lower response in the prefrontal cortices bilaterally (p<0.005). Patients, but not controls, had lower functional brain response during a more complex working memory task compared with a simpler one. In conclusion, women with CS in long-term remission have reduced functional brain responses during episodic and working memory testing. This observation extends previous findings showing long-term adverse effects of severe hypercortisolaemia on brain function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanical origins of rightward torsion in early chick brain development

NASA Astrophysics Data System (ADS)

Chen, Zi; Guo, Qiaohang; Dai, Eric; Taber, Larry

2015-03-01

During early development, the neural tube of the chick embryo undergoes a combination of progressive ventral bending and rightward torsion. This torsional deformation is one of the major organ-level left-right asymmetry events in development. Previous studies suggested that bending is mainly due to differential growth, however, the mechanism for torsion remains poorly understood. Since the heart almost always loops rightwards that the brain twists, researchers have speculated that heart looping affects the direction of brain torsion. However, direct evidence is lacking, nor is the mechanical origin of such torsion understood. In our study, experimental perturbations show that the bending and torsional deformations in the brain are coupled and that the vitelline membrane applies an external load necessary for torsion to occur. Moreover, the asymmetry of the looping heart gives rise to the chirality of the twisted brain. A computational model and a 3D printed physical model are employed to help interpret these findings. Our work clarifies the mechanical origins of brain torsion and the associated left-right asymmetry, and further reveals that the asymmetric development in one organ can induce the asymmetry of another developing organ through mechanics, reminiscent of D'Arcy Thompson's view of biological form as ``diagram of forces''. Z.C. is supported by the Society in Science - Branco Weiss fellowship, administered by ETH Zurich. L.A.T acknowledges the support from NIH Grants R01 GM075200 and R01 NS070918.

STAT3 precedes HIF1α transcriptional responses to oxygen and oxygen and glucose deprivation in human brain pericytes.

PubMed

Carlsson, Robert; Özen, Ilknur; Barbariga, Marco; Gaceb, Abderahim; Roth, Michaela; Paul, Gesine

2018-01-01

Brain pericytes are important to maintain vascular integrity of the neurovascular unit under both physiological and ischemic conditions. Ischemic stroke is known to induce an inflammatory and hypoxic response due to the lack of oxygen and glucose in the brain tissue. How this early response to ischemia is molecularly regulated in pericytes is largely unknown and may be of importance for future therapeutic targets. Here we evaluate the transcriptional responses in in vitro cultured human brain pericytes after oxygen and/or glucose deprivation. Hypoxia has been widely known to stabilise the transcription factor hypoxia inducible factor 1-alpha (HIF1α) and mediate the induction of hypoxic transcriptional programs after ischemia. However, we find that the transcription factors Jun Proto-Oncogene (c-JUN), Nuclear Factor Of Kappa Light Polypeptide Gene Enhancer In B-Cells (NFκB) and signal transducer and activator of transcription 3 (STAT3) bind genes regulated after 2hours (hs) of omitted glucose and oxygen before HIF1α. Potent HIF1α responses require 6hs of hypoxia to substantiate transcriptional regulation comparable to either c-JUN or STAT3. Phosphorylated STAT3 protein is at its highest after 5 min of oxygen and glucose (OGD) deprivation, whereas maximum HIF1α stabilisation requires 120 min. We show that STAT3 regulates angiogenic and metabolic pathways before HIF1α, suggesting that HIF1α is not the initiating trans-acting factor in the response of pericytes to ischemia.

Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities.

PubMed

Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E

2017-07-01

Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P < .001; right: 0.810, 0.753; P < .01). Altered location and depth patterns of sulcal basins were the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.

Toward a conceptual framework for early brain and behavior development in autism

PubMed Central

Piven, J; Elison, J T; Zylka, M J

2017-01-01

Studies of infant siblings of older autistic probands, who are at elevated risk for autism, have demonstrated that the defining features of autism are not present in the first year of life but emerge late in the first and into the second year. A recent longitudinal neuroimaging study of high-risk siblings revealed a specific pattern of brain development in infants later diagnosed with autism, characterized by cortical surface area hyper-expansion in the first year followed by brain volume overgrowth in the second year that is associated with the emergence of autistic social deficits. Together with new observations from genetically defined autism risk alleles and rodent model, these findings suggest a conceptual framework for the early, post-natal development of autism. This framework postulates that an increase in the proliferation of neural progenitor cells and hyper-expansion of cortical surface area in the first year, occurring during a pre-symptomatic period characterized by disrupted sensorimotor and attentional experience, leads to altered experience-dependent neuronal development and decreased elimination of neuronal processes. This process is linked to brain volume overgrowth and disruption of the refinement of neural circuit connections and is associated with the emergence of autistic social deficits in the second year of life. A better understanding of the timing of developmental brain and behavior mechanisms in autism during infancy, a period which precedes the emergence of the defining features of this disorder, will likely have important implications for designing rational approaches to early intervention. PMID:28937691

To Stroop or Not to Stroop: Sex-Related Differences in Brain-Behavior Associations During Early Childhood

PubMed Central

Cuevas, Kimberly; Calkins, Susan D.; Bell, Martha Ann

2015-01-01

Executive functions (EFs) are linked with optimal cognitive and social-emotional development. Despite behavioral evidence of sex differences in early childhood EF, little is known about potential sex differences in corresponding brain-behavior associations. The present study examined changes in 4-year-olds’ 6–9 Hz EEG power in response to increased executive processing demands (i.e., “Stroop-like” vs. “non-Stroop” day-night tasks). Although there were no sex differences in task performance, an examination of multiple scalp electrode sites revealed that boys exhibited more widespread changes in EEG power as compared to girls. Further, multiple regression analyses controlling for maternal education and non-EF performance indicated that individual differences in boys’ and girls’ EF performance were associated with different frontal neural correlates (i.e., different frontal scalp sites and different measures of EEG power). These data reveal valuable information concerning sex differences in the neural systems underlying executive processing during early childhood. PMID:26681615

Early Brain Injury Associated with Systemic Inflammation After Subarachnoid Hemorrhage.

PubMed

Savarraj, Jude; Parsha, Kaushik; Hergenroeder, Georgene; Ahn, Sungho; Chang, Tiffany R; Kim, Dong H; Choi, H Alex

2018-04-01

Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) is defined as brain injury occurring within 72 h of aneurysmal rupture. Although EBI is the most significant predictor of outcomes after aSAH, its underlying pathophysiology is not well understood. We hypothesize that EBI after aSAH is associated with an increase in peripheral inflammation measured by cytokine expression levels and changes in associations between cytokines. aSAH patients were enrolled into a prospective observational study and were assessed for markers of EBI: global cerebral edema (GCE), subarachnoid hemorrhage early brain edema score (SEBES), and Hunt-Hess grade. Serum samples collected at ≤ 48 h of admission were analyzed using multiplex bead-based assays to determine levels of 13 pro- and anti-inflammatory cytokines. Pairwise correlation coefficients between cytokines were represented as networks. Cytokine levels and differences in correlation networks were compared between EBI groups. Of the 71 patients enrolled in the study, 17 (24%) subjects had GCE, 31 (44%) subjects had SEBES ≥ 3, and 21 (29%) had HH ≥ 4. IL-6 was elevated in groups with GCE, SEBES ≥ 3, and HH ≥ 4. MIP1β was independently associated with high-grade SEBES. Correlation network analysis suggests higher systematic inflammation in subjects with SEBES ≥ 3. EBI after SAH is associated with increased levels of specific cytokines. Peripheral levels of IL-10, IL-6, and MIP1β may be important markers of EBI. Investigating systematic correlations in addition to expression levels of individual cytokines may offer deeper insight into the underlying mechanisms related to EBI.

Exposure to dim light at night during early development increases adult anxiety-like responses.

PubMed

Borniger, Jeremy C; McHenry, Zachary D; Abi Salloum, Bachir A; Nelson, Randy J

2014-06-22

Early experiences produce effects that may persist throughout life. Therefore, to understand adult phenotype, it is important to investigate the role of early environmental stimuli in adult behavior and health. Artificial light at night (LAN) is an increasingly common phenomenon throughout the world. However, animals, including humans, evolved under dark night conditions. Many studies have revealed affective, immune, and metabolic alterations provoked by aberrant light exposure and subsequent circadian disruption. Pups are receptive to entraining cues from the mother and then light early during development, raising the possibility that the early life light environment may influence subsequent behavior. Thus, to investigate potential influences of early life exposure to LAN on adult phenotype, we exposed mice to dim (~5 lux; full spectrum white light) or dark (~0 lux) nights pre- and/or postnatally. After weaning at 3 weeks of age, all mice were maintained in dark nights until adulthood (9 weeks of age) when behavior was assessed. Mice exposed to dim light in early life increased anxiety-like behavior and fearful responses on the elevated plus maze and passive avoidance tests. These mice also displayed reduced growth rates, which ultimately normalized during adolescence. mRNA expression of brain derived neurotrophic factor (BDNF), a neurotrophin previously linked to early life environment and adult phenotype, was not altered in the prefrontal cortex or hippocampus by early life LAN exposure. Serum corticosterone concentrations were similar between groups at weaning, suggesting that early life LAN does not elicit a long-term physiologic stress response. Dim light exposure did not influence behavior on the open field, novel object, sucrose anhedonia, or forced swim tests. Our data highlight the potential deleterious consequences of low levels of light during early life to development and subsequent behavior. Whether these changes are due to altered maternal behavior

Effects of maternal separation, early handling, and gonadal sex on regional metabolic capacity of the preweanling rat brain

PubMed Central

Spivey, Jaclyn M.; Padilla, Eimeira; Shumake, Jason D.; Gonzalez-Lima, F.

2010-01-01

This is the first study to assess the effects of mother-infant separation on regional metabolic capacity in the preweanling rat brain. Mother-infant separation is generally known to be stressful for rat pups. Holtzman adolescent rats show a depressive-like behavioral phenotype after maternal separation during the preweanling period. However, information is lacking on the effects of maternal separation on the brains of rat pups. We addressed this issue by mapping the brains of preweanling Holtzman rat pups using cytochrome oxidase histochemistry, which reflects long-term changes in brain metabolic capacity, following two weeks of repeated, prolonged maternal separation, and compared this to both early handled and non-handled pups. Quantitative image analysis revealed that maternal separation reduced cytochrome oxidase activity in the medial prefrontal cortex and nucleus accumbens shell. Maternal separation reduced prefrontal cytochrome oxidase to a greater degree in female pups than in males. Early handling reduced cytochrome oxidase activity in the posterior parietal cortex, ventral tegmental area, and subiculum, but increased cytochrome oxidase activity in the lateral frontal cortex. The sex-dependent effects of early handling on cytochrome oxidase activity were limited to the medial prefrontal cortex. Regardless of separation group, females had greater cytochrome oxidase activity in the habenula and ventral tegmental area compared to males. These findings suggest that early life mother-infant separation results in dysfunction of prefrontal and mesolimbic regions in the preweanling rat brain that may contribute to behavioral changes later in life. PMID:20969837

Early and Later Life Stress Alter Brain Activity and Sleep in Rats

PubMed Central

Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

2013-01-01

Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2–14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way. PMID:23922857

Overweight adolescents' brain response to sweetened beverages mirrors addiction pathways.

PubMed

Feldstein Ewing, Sarah W; Claus, Eric D; Hudson, Karen A; Filbey, Francesca M; Yakes Jimenez, Elizabeth; Lisdahl, Krista M; Kong, Alberta S

2017-08-01

Many adolescents struggle with overweight/obesity, which exponentially increases in the transition to adulthood. Overweight/obesity places youth at risk for serious health conditions, including type 2 diabetes. In adults, neural substrates implicated in addiction (e.g., orbitofrontal cortex (OFC), striatum, amygdala, and ventral tegmental area) have been found to be relevant to risk for overweight/obesity. In this study, we examined three hypotheses to disentangle the potential overlap between addiction and overweight/obesity processing by examining (1) brain response to high vs. low calorie beverages, (2) the strength of correspondence between biometrics, including body mass index (BMI) and insulin resistance, and brain response and (3) the relationship between a measure of food addiction and brain response using an established fMRI gustatory cue exposure task with a sample of overweight/obese youth (M age = 16.46; M BMI = 33.1). Greater BOLD response was observed across the OFC, inferior frontal gyrus (IFG), nucleus accumbens, right amygdala, and additional frontoparietal and temporal regions in neural processing of high vs. low calorie beverages. Further, BMI scores positively correlated with BOLD activation in the high calorie > low calorie contrast in the right postcentral gyrus and central operculum. Insulin resistance positively correlated with BOLD activation across the bilateral middle/superior temporal gyrus, left OFC, and superior parietal lobe. No relationships were observed between measures of food addiction and brain response. These findings support the activation of parallel addiction-related neural pathways in adolescents' high calorie processing, while also suggesting the importance of refining conceptual and neurocognitive models to fit this developmental period.

MRI patterns in prolonged low response states following traumatic brain injury in children and adolescents.

PubMed

Patrick, Peter D; Mabry, Jennifer L; Gurka, Matthew J; Buck, Marcia L; Boatwright, Evelyn; Blackman, James A

2007-01-01

To explore the relationship between location and pattern of brain injury identified on MRI and prolonged low response state in children post-traumatic brain injury (TBI). This observational study compared 15 children who spontaneously recovered within 30 days post-TBI to 17 who remained in a prolonged low response state. 92.9% of children with brain stem injury were in the low response group. The predicted probability was 0.81 for brain stem injury alone, increasing to 0.95 with a regional pattern of injury to the brain stem, basal ganglia, and thalamus. Low response state in children post-TBI is strongly correlated with two distinctive regions of injury: the brain stem alone, and an injury pattern to the brain stem, basal ganglia, and thalamus. This study demonstrates the need for large-scale clinical studies using MRI as a tool for outcome assessment in children and adolescents following severe TBI.

Functional MR imaging assessment of a non-responsive brain injured patient.

PubMed

Moritz, C H; Rowley, H A; Haughton, V M; Swartz, K R; Jones, J; Badie, B

2001-10-01

Functional magnetic resonance imaging (fMRI) was requested to assist in the evaluation of a comatose 38-year-old woman who had sustained multiple cerebral contusions from a motor vehicle accident. Previous electrophysiologic studies suggested absence of thalamocortical processing in response to median nerve stimulation. Whole-brain fMRI was performed utilizing visual, somatosensory, and auditory stimulation paradigms. Results demonstrated intact task-correlated sensory and cognitive blood oxygen level dependent (BOLD) hemodynamic response to stimuli. Electrodiagnostic studies were repeated and evoked potentials indicated supratentorial recovery in the cerebrum. At 3-months post trauma the patient had recovered many cognitive & sensorimotor functions, accurately reflecting the prognostic fMRI evaluation. These results indicate that fMRI examinations may provide a useful evaluation for brain function in non-responsive brain trauma patients.

Early life conditions that impact song learning in male zebra finches also impact neural and behavioral responses to song in females.

PubMed

Sewall, Kendra B; Anderson, Rindy C; Soha, Jill A; Peters, Susan; Nowicki, Stephen

2018-04-20

Early life stressors can impair song in songbirds by negatively impacting brain development and subsequent learning. Even in species in which only males sing, early life stressors might also impact female behavior and its underlying neural mechanisms, but fewer studies have examined this possibility. We manipulated brood size in zebra finches to simultaneously examine the effects of developmental stress on male song learning and female behavioral and neural response to song. Although adult male HVC volume was unaffected, we found that males from larger broods imitated tutor song less accurately. In females, early condition did not affect the direction of song preference: all females preferred tutor song over unfamiliar song in an operant test. However, treatment did affect the magnitude of behavioral response to song: females from larger broods responded less during song preference trials. This difference in activity level did not reflect boldness per se, as a separate measure of this trait did not differ with brood size. Additionally, in females we found a treatment effect on expression of the immediate early gene ZENK in response to tutor song in brain regions involved in song perception (dNCM) and social motivation (LSc.vl, BSTm, TnA), but not in a region implicated in song memory (CMM). These results are consistent with the hypothesis that developmental stressors that impair song learning in male zebra finches also influence perceptual and/or motivational processes in females. However, our results suggest that the learning of tutor song by females is robust to disturbance by developmental stress. © 2018 Wiley Periodicals, Inc. Develop Neurobiol, 2018. © 2018 Wiley Periodicals, Inc.

Early Palliative Care for Patients With Brain Metastases Decreases Inpatient Admissions and Need for Imaging Studies.

PubMed

Habibi, Akram; Wu, S Peter; Gorovets, Daniel; Sansosti, Alexandra; Kryger, Marc; Beaudreault, Cameron; Chung, Wei-Yi; Shelton, Gary; Silverman, Joshua; Lowy, Joseph; Kondziolka, Douglas

2018-01-01

Early encounters with palliative care (PC) can influence health-care utilization, clinical outcome, and cost. To study the effect of timing of PC encounters on brain metastasis patients at an academic medical center. All patients diagnosed with brain metastases from January 2013 to August 2015 at a single institution with inpatient and/or outpatient PC records available for review (N = 145). Early PC was defined as having a PC encounter within 8 weeks of diagnosis with brain metastases; late PC was defined as having PC after 8 weeks of diagnosis. Propensity score matched cohorts of early (n = 46) and late (n = 46) PC patients were compared to control for differences in age, gender, and Karnofsky Performance Status (KPS) at diagnosis. Details of the palliative encounter, patient outcomes, and health-care utilization were collected. Early PC versus late PC patients had no differences in baseline KPS, age, or gender. Early PC patients had significantly fewer number of inpatient visits per patient (1.5 vs 2.9; P = .004), emergency department visits (1.2 vs 2.1; P = .006), positron emission tomography/computed tomography studies (1.2 vs 2.7, P = .005), magnetic resonance imaging scans (5.8 vs 8.1; P = .03), and radiosurgery procedures (0.6 vs 1.3; P < .001). There were no differences in overall survival (median 8.2 vs 11.2 months; P = .2). Following inpatient admissions, early PC patients were more likely to be discharged home (59% vs 35%; P = .04). Timely PC consultations are advisable in this patient population and can reduce health-care utilization.

Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity.

PubMed

Drew Sayer, R; Tamer, Gregory G; Chen, Ningning; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

2016-10-01

The brain's reward system influences ingestive behavior and subsequently obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. This study sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n = 16) and men (n = 12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the two testing days. Mean fasting-state brain responses on day 2 were reduced compared with day 1 in the left insula and right amygdala, but mean day 1 and day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies. © 2016 The Obesity Society.

Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease.

PubMed

Muñoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe

2018-02-07

Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks

Effects of unexpected chords and of performer's expression on brain responses and electrodermal activity.

PubMed

Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

2008-07-09

There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music.

Effects of Unexpected Chords and of Performer's Expression on Brain Responses and Electrodermal Activity

PubMed Central

Koelsch, Stefan; Kilches, Simone; Steinbeis, Nikolaus; Schelinski, Stefanie

2008-01-01

Background There is lack of neuroscientific studies investigating music processing with naturalistic stimuli, and brain responses to real music are, thus, largely unknown. Methodology/Principal Findings This study investigates event-related brain potentials (ERPs), skin conductance responses (SCRs) and heart rate (HR) elicited by unexpected chords of piano sonatas as they were originally arranged by composers, and as they were played by professional pianists. From the musical excerpts played by the pianists (with emotional expression), we also created versions without variations in tempo and loudness (without musical expression) to investigate effects of musical expression on ERPs and SCRs. Compared to expected chords, unexpected chords elicited an early right anterior negativity (ERAN, reflecting music-syntactic processing) and an N5 (reflecting processing of meaning information) in the ERPs, as well as clear changes in the SCRs (reflecting that unexpected chords also elicited emotional responses). The ERAN was not influenced by emotional expression, whereas N5 potentials elicited by chords in general (regardless of their chord function) differed between the expressive and the non-expressive condition. Conclusions/Significance These results show that the neural mechanisms of music-syntactic processing operate independently of the emotional qualities of a stimulus, justifying the use of stimuli without emotional expression to investigate the cognitive processing of musical structure. Moreover, the data indicate that musical expression affects the neural mechanisms underlying the processing of musical meaning. Our data are the first to reveal influences of musical performance on ERPs and SCRs, and to show physiological responses to unexpected chords in naturalistic music. PMID:18612459

The brain parenchyma has a type I interferon response that can limit virus spread.

PubMed

Drokhlyansky, Eugene; Göz Aytürk, Didem; Soh, Timothy K; Chrenek, Ryan; O'Loughlin, Elaine; Madore, Charlotte; Butovsky, Oleg; Cepko, Constance L

2017-01-03

The brain has a tightly regulated environment that protects neurons and limits inflammation, designated "immune privilege." However, there is not an absolute lack of an immune response. We tested the ability of the brain to initiate an innate immune response to a virus, which was directly injected into the brain parenchyma, and to determine whether this response could limit viral spread. We injected vesicular stomatitis virus (VSV), a transsynaptic tracer, or naturally occurring VSV-derived defective interfering particles (DIPs), into the caudate-putamen (CP) and scored for an innate immune response and inhibition of virus spread. We found that the brain parenchyma has a functional type I interferon (IFN) response that can limit VSV spread at both the inoculation site and among synaptically connected neurons. Furthermore, we characterized the response of microglia to VSV infection and found that infected microglia produced type I IFN and uninfected microglia induced an innate immune response following virus injection.

Half brain irradiation in a murine model of breast cancer brain metastasis: magnetic resonance imaging and histological assessments of dose-response.

PubMed

Zarghami, Niloufar; Murrell, Donna H; Jensen, Michael D; Dick, Frederick A; Chambers, Ann F; Foster, Paula J; Wong, Eugene

2018-06-01

Brain metastasis is becoming increasingly prevalent in breast cancer due to improved extra-cranial disease control. With emerging availability of modern image-guided radiation platforms, mouse models of brain metastases and small animal magnetic resonance imaging (MRI), we examined brain metastases' responses from radiotherapy in the pre-clinical setting. In this study, we employed half brain irradiation to reduce inter-subject variability in metastases dose-response evaluations. Half brain irradiation was performed on a micro-CT/RT system in a human breast cancer (MDA-MB-231-BR) brain metastasis mouse model. Radiation induced DNA double stranded breaks in tumors and normal mouse brain tissue were quantified using γ-H2AX immunohistochemistry at 30 min (acute) and 11 days (longitudinal) after half-brain treatment for doses of 8, 16 and 24 Gy. In addition, tumor responses were assessed volumetrically with in-vivo longitudinal MRI and histologically for tumor cell density and nuclear size. In the acute setting, γ-H2AX staining in tumors saturated at higher doses while normal mouse brain tissue continued to increase linearly in the phosphorylation of H2AX. While γ-H2AX fluorescence intensities returned to the background level in the brain 11 days after treatment, the residual γ-H2AX phosphorylation in the radiated tumors remained elevated compared to un-irradiated contralateral tumors. With radiation, MRI-derived relative tumor growth was significantly reduced compared to the un-irradiated side. While there was no difference in MRI tumor volume growth between 16 and 24 Gy, there was a significant reduction in tumor cell density from histology with increasing dose. In the longitudinal study, nuclear size in the residual tumor cells increased significantly as the radiation dose was increased. Radiation damages to the DNAs in the normal brain parenchyma are resolved over time, but remain unrepaired in the treated tumors. Furthermore, there is a radiation dose

Early planarian brain regeneration is independent of blastema polarity mediated by the Wnt/β-catenin pathway.

PubMed

Iglesias, Marta; Almuedo-Castillo, Maria; Aboobaker, A Aziz; Saló, Emili

2011-10-01

Analysis of anteroposterior (AP) axis specification in regenerating planarian flatworms has shown that Wnt/β-catenin signaling is required for posterior specification and that the FGF-like receptor molecule nou-darake (ndk) may be involved in restricting brain regeneration to anterior regions. The relationship between re-establishment of AP identity and correct morphogenesis of the brain is, however, still poorly understood. Here we report the characterization of two axin paralogs in the planarian Schmidtea mediterranea. Although Axins are well known negative regulators of Wnt/β-catenin signaling, no role in AP specification has previously been reported for axin genes in planarians. We show that silencing of Smed-axin genes by RNA interference (RNAi) results in two-tailed planarians, a phenotype previously reported after silencing of Smed-APC-1, another β-catenin inhibitor. More strikingly, we show for the first time that while early brain formation at anterior wounds remains unaffected, subsequent development of the brain is blocked in the two-tailed planarians generated after silencing of Smed-axin genes and Smed-APC-1. These findings suggest that the mechanisms underlying early brain formation can be uncoupled from the specification of AP identity by the Wnt/β-catenin pathway. Finally, the posterior expansion of the brain observed following Smed-ndk RNAi is enhanced by silencing Smed-APC-1, revealing an indirect relationship between the FGFR/Ndk and Wnt/β-catenin signaling systems in establishing the posterior limits of brain differentiation. Copyright © 2011 Elsevier Inc. All rights reserved.

Trajectories of Early Brain Volume Development in Fragile X and Autism RH: Trajectory of Brain Volume in Fragile X

PubMed Central

Hazlett, Heather Cody; Poe, Michele D.; Lightbody, Amy A.; Styner, Martin; MacFall, James R.; Reiss, Allan L.; Piven, Joseph

2012-01-01

Objective To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared to a comparison group (controls) and a group with idiopathic autism. Method The study included 53 boys between 18–42 months of age with FXS, 68 boys with idiopathic autism (ASD), and a comparison group of 50 typically-developing and developmentally-delayed controls. We examined structural brain volumes using magnetic resonance imaging (MRI) across two timepoints between ages 2–3 and 4–5 years and examined total brain volumes and regional (lobar) tissue volumes. Additionally, we studied a selected group of subcortical structures implicated in the behavioral features of FXS (e.g., basal ganglia, hippocampus, amygdala). Results Children with FXS had greater global brain volumes compared to controls, but were not different than children with idiopathic autism, and the rate of brain growth between ages 2 and 5 paralleled that seen in controls. In contrast to the children with idiopathic autism who had generalized cortical lobe enlargement, the children with FXS showed a specific enlargement in temporal lobe white matter, cerebellar gray matter, and caudate nucleus, but significantly smaller amygdala. Conclusions This structural longitudinal MRI study of preschoolers with FXS observed generalized brain overgrowth in FXS compared to controls, evident at age 2 and maintained across ages 4–5. We also find different patterns of brain growth that distinguishes boys with FXS from children with idiopathic autism. PMID:22917205

Post-treatment Vascular Leakage and Inflammatory Responses around Brain Cysts in Porcine Neurocysticercosis

PubMed Central

Mahanty, Siddhartha; Orrego, Miguel Angel; Mayta, Holger; Marzal, Miguel; Cangalaya, Carla; Paredes, Adriana; Gonzales-Gustavson, Eloy; Arroyo, Gianfranco; Gonzalez, Armando E.; Guerra-Giraldez, Cristina; García, Hector H.; Nash, Theodore E.

2015-01-01

Cysticidal treatment of neurocysticercosis, an infection of humans and pig brains with Taenia solium, results in an early inflammatory response directed to cysts causing seizures and focal neurological manifestations. Treatment-induced pericystic inflammation and its association with blood brain barrier (BBB) dysfunction, as determined by Evans blue (EB) extravasation, was studied in infected untreated and anthelmintic-treated pigs. We compared the magnitude and extent of the pericystic inflammation, presence of EB-stained capsules, the level of damage to the parasite, expression of genes for proinflammatory and regulatory cytokines, chemokines, and tissue remodeling by quantitative PCR assays between treated and untreated infected pigs and between EB-stained (blue) and non stained (clear) cysts. Inflammatory scores were higher in pericystic tissues from EB-stained cysts compared to clear cysts from untreated pigs and also from anthelmintic-treated pigs 48 hr and 120 hr after treatment. The degree of inflammation correlated with the severity of cyst wall damage and both increased significantly at 120 hours. Expression levels of the proinflammatory genes for IL-6, IFN-γ, TNF-α were higher in EB-stained cysts compared to clear cysts and unaffected brain tissues, and were generally highest at 120 hr. Additionally, expression of some markers of immunoregulatory activity (IL-10, IL-2Rα) were decreased in EB-stained capsules. An increase in other markers for regulatory T cells (CTLA4, FoxP3) was found, as well as significant increases in expression of two metalloproteases, MMP1 and MMP2 at 48 hr and 120 hr post-treatment. We conclude that the increase in severity of the inflammation caused by treatment is accompanied by both a proinflammatory and a complex regulatory response, largely limited to pericystic tissues with compromised vascular integrity. Because treatment induced inflammation occurs in porcine NCC similar to that in human cases, this model can be used to

Repetitive Religious Chanting Modulates the Late-Stage Brain Response to Fear- and Stress-Provoking Pictures.

PubMed

Gao, Junling; Fan, Jicong; Wu, Bonnie W; Halkias, Georgios T; Chau, Maggie; Fung, Peter C; Chang, Chunqi; Zhang, Zhiguo; Hung, Yeung-Sam; Sik, Hinhung

2016-01-01

similar research findings on Christian religious practices and brain responses to negative stimuli. Hence, prayer/religious practices may have cross-cultural universality in emotion regulation. This study shows for the first time that Buddhist chanting, or in a broader sense, repetition of religious prayers will not modulate brain responses to negative stimuli during the early perceptual stage, but only during the late-stage emotional/cognitive processing.

Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity

PubMed Central

Sayer, R Drew; Tamer, Gregory G; Chen, Ningning; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

2016-01-01

Objective The brain’s reward system influences ingestive behavior and subsequently, obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. We sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. Methods A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n=16) and men (n=12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the 2 testing days. Results Mean fasting-state brain responses on Day 2 were reduced compared to Day 1 in the left insula and right amygdala, but mean Day 1 and Day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. Conclusion fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility, but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies. PMID:27542906

Brain Development in Autism: Early Overgrowth Followed by Premature Arrest of Growth

ERIC Educational Resources Information Center

Courchesne, Eric

2004-01-01

Due to the relatively late age of clinical diagnosis of autism, the early brain pathology of children with autism has remained largely unstudied. The increased use of retrospective measures such as head circumference, along with a surge of MRI studies of toddlers with autism, have opened a whole new area of research and discovery. Recent studies…

Trajectories of Early Brain Volume Development in Fragile X Syndrome and Autism

ERIC Educational Resources Information Center

Hazlett, Heather Cody; Poe, Michele D.; Lightbody, Amy A.; Styner, Martin; MacFall, James R.; Reiss, Allan L.; Piven, Joseph

2012-01-01

Objective: To examine patterns of early brain growth in young children with fragile X syndrome (FXS) compared with a comparison group (controls) and a group with idiopathic autism. Method: The study included 53 boys 18 to 42 months of age with FXS, 68 boys with idiopathic autism (autism spectrum disorder), and a comparison group of 50 typically…

Assessing paedophilia based on the haemodynamic brain response to face images.

PubMed

Ponseti, Jorge; Granert, Oliver; Van Eimeren, Thilo; Jansen, Olav; Wolff, Stephan; Beier, Klaus; Deuschl, Günther; Huchzermeier, Christian; Stirn, Aglaja; Bosinski, Hartmut; Roman Siebner, Hartwig

2016-01-01

Objective assessment of sexual preferences may be of relevance in the treatment and prognosis of child sexual offenders. Previous research has indicated that this can be achieved by pattern classification of brain responses to sexual child and adult images. Our recent research showed that human face processing is tuned to sexual age preferences. This observation prompted us to test whether paedophilia can be inferred based on the haemodynamic brain responses to adult and child faces. Twenty-four men sexually attracted to prepubescent boys or girls (paedophiles) and 32 men sexually attracted to men or women (teleiophiles) were exposed to images of child and adult, male and female faces during a functional magnetic resonance imaging (fMRI) session. A cross-validated, automatic pattern classification algorithm of brain responses to facial stimuli yielded four misclassified participants (three false positives), corresponding to a specificity of 91% and a sensitivity of 95%. These results indicate that the functional response to facial stimuli can be reliably used for fMRI-based classification of paedophilia, bypassing the problem of showing child sexual stimuli to paedophiles.

Variability in Reward Responsivity and Obesity: Evidence from Brain Imaging Studies

PubMed Central

Burger, Kyle S.; Stice, Eric

2012-01-01

Advances in neuroimaging techniques have provided insight into the role of the brain in the regulation of food intake and weight. Growing evidence demonstrate that energy dense, palatable foods elicit similar responses in reward-related brain regions that mimic those of addictive substances. Currently, various models of obesity’s relation to reward from food have been theorized. There is evidence to support a theory of hypo-responsivity of reward regions to food, where individuals consume excess amounts to overcome this reward deficit. There is also data to support a theory of hyper-responsivity of reward regions, where individuals who experience greater reward from food intake are at risk for overeating. However, these seemingly discordant theories are static in nature and do not account for the possible effects of repeated overeating on brain responsivity to food and initial vulnerability factors. Here we review data that support these theories and propose a dynamic vulnerability model of obesity that appears to offer a parsimonious theory that accommodates extant findings. PMID:21999692

Submillisecond unmasked subliminal visual stimuli evoke electrical brain responses.

PubMed

Sperdin, Holger F; Spierer, Lucas; Becker, Robert; Michel, Christoph M; Landis, Theodor

2015-04-01

Subliminal perception is strongly associated to the processing of meaningful or emotional information and has mostly been studied using visual masking. In this study, we used high density 256-channel EEG coupled with an liquid crystal display (LCD) tachistoscope to characterize the spatio-temporal dynamics of the brain response to visual checkerboard stimuli (Experiment 1) or blank stimuli (Experiment 2) presented without a mask for 1 ms (visible), 500 µs (partially visible), and 250 µs (subliminal) by applying time-wise, assumption-free nonparametric randomization statistics on the strength and on the topography of high-density scalp-recorded electric field. Stimulus visibility was assessed in a third separate behavioral experiment. Results revealed that unmasked checkerboards presented subliminally for 250 µs evoked weak but detectable visual evoked potential (VEP) responses. When the checkerboards were replaced by blank stimuli, there was no evidence for the presence of an evoked response anymore. Furthermore, the checkerboard VEPs were modulated topographically between 243 and 296 ms post-stimulus onset as a function of stimulus duration, indicative of the engagement of distinct configuration of active brain networks. A distributed electrical source analysis localized this modulation within the right superior parietal lobule near the precuneus. These results show the presence of a brain response to submillisecond unmasked subliminal visual stimuli independently of their emotional saliency or meaningfulness and opens an avenue for new investigations of subliminal stimulation without using visual masking. © 2014 Wiley Periodicals, Inc.

Brain responses to food images during the early and late follicular phase of the menstrual cycle in healthy young women: relation to fasting and feeding1234

PubMed Central

Ziemke, Florencia; Magkos, Faidon; Barrios, Fernando A; Brinkoetter, Mary; Boyd, Ingrid; Rifkin-Graboi, Anne; Yannakoulia, Mary; Rojas, Rafael; Pascual-Leone, Alvaro; Mantzoros, Christos S

2011-01-01

Background: Food intake fluctuates throughout the menstrual cycle; it is greater during the early follicular and luteal phases than in the late follicular (periovulatory) phase. Ovarian steroids can influence brain areas that process food-related information, but the specific contribution of individual hormones and the importance of the prandial state remain unknown. Objective: The objective was to examine whether brain activation during food visualization is affected by changes in estradiol concentration in the fasted and fed conditions. Design: Nine eumenorrheic, lean young women [mean (±SD) age: 26.2 ± 3.2 y; body mass index (in kg/m2): 22.4 ± 1.2] completed 2 visits, one in the early (low estradiol) and one in the late (high estradiol) follicular phase of their menstrual cycle. At each visit, subjects underwent functional magnetic resonance imaging while they viewed food and nonfood images, before and after a standardized meal. Region-of-interest analysis was used to examine the effect of follicular phase and prandial state on brain activation (food > nonfood contrast) and its association with estradiol concentration. Results: Differences were identified in the inferior frontal and fusiform gyri. In these areas, visualization of food elicited greater activation in the fed state than during fasting but only in the late follicular phase, when estradiol concentration was high. The change in estradiol concentration across the follicular phase (late minus early) was inversely correlated with the change in fusiform gyrus activation in the fasted state but not in the fed state. Conclusion: Our findings suggest that estradiol may reduce food intake by decreasing sensitivity to food cues in the ventral visual pathway under conditions of energy deprivation. This trial was registered at clinicaltrials.gov as NCT00130117. PMID:21593494

Cholinesterase inhibition modulates visual and attentional brain responses in Alzheimer's disease and health.

PubMed

Bentley, Paul; Driver, Jon; Dolan, Ray J

2008-02-01

Visuo-attentional deficits occur early in Alzheimer's disease (AD) and are considered more responsive to pro-cholinergic therapy than characteristic memory disturbances. We hypothesised that neural responses in AD during visuo-attentional processing would be impaired relative to controls, yet partially susceptible to improvement with the cholinesterase inhibitor physostigmine. We studied 16 mild AD patients and 17 age-matched healthy controls, using fMRI-scanning to enable within-subject placebo-controlled comparisons of effects of physostigmine on stimulus- and attention- related brain activations, plus between-group comparisons for these. Subjects viewed face or building stimuli while performing a shallow judgement (colour of image) or a deep judgement (young/old age of depicted face or building). Behaviourally, AD subjects performed slower than controls in both tasks, while physostigmine benefited the patients for the more demanding age-judgement task. Stimulus-selective (face minus building, and vice versa) BOLD signals in precuneus and posterior parahippocampal cortex were attenuated in patients relative to controls, but increased following physostigmine. By contrast, face-selective responses in fusiform cortex were not impaired in AD and showed decreases following physostigmine for both groups. Task-dependent responses in right parietal and prefrontal cortices were diminished in AD but improved following physostigmine. A similar pattern of group and treatment effects was observed in two extrastriate cortical regions that showed physostigmine-induced enhancement of stimulus-selectivity for the deep versus shallow task. Finally, for the healthy group, physostigmine decreased stimulus and task-dependent effects, partly due to an exaggeration of selectivity during the shallow relative to deep task. The differences in brain activations between groups and treatments were not attributable merely to performance (reaction time) differences. Our results demonstrate

The Role of Visual and Semantic Properties in the Emergence of Category-Specific Patterns of Neural Response in the Human Brain.

PubMed

Coggan, David D; Baker, Daniel H; Andrews, Timothy J

2016-01-01

Brain-imaging studies have found distinct spatial and temporal patterns of response to different object categories across the brain. However, the extent to which these categorical patterns of response reflect higher-level semantic or lower-level visual properties of the stimulus remains unclear. To address this question, we measured patterns of EEG response to intact and scrambled images in the human brain. Our rationale for using scrambled images is that they have many of the visual properties found in intact images, but do not convey any semantic information. Images from different object categories (bottle, face, house) were briefly presented (400 ms) in an event-related design. A multivariate pattern analysis revealed categorical patterns of response to intact images emerged ∼80-100 ms after stimulus onset and were still evident when the stimulus was no longer present (∼800 ms). Next, we measured the patterns of response to scrambled images. Categorical patterns of response to scrambled images also emerged ∼80-100 ms after stimulus onset. However, in contrast to the intact images, distinct patterns of response to scrambled images were mostly evident while the stimulus was present (∼400 ms). Moreover, scrambled images were able to account only for all the variance in the intact images at early stages of processing. This direct manipulation of visual and semantic content provides new insights into the temporal dynamics of object perception and the extent to which different stages of processing are dependent on lower-level or higher-level properties of the image.

Abnormal hemodynamic response to forepaw stimulation in rat brain after cocaine injection

NASA Astrophysics Data System (ADS)

Chen, Wei; Park, Kicheon; Choi, Jeonghun; Pan, Yingtian; Du, Congwu

2015-03-01

Simultaneous measurement of hemodynamics is of great importance to evaluate the brain functional changes induced by brain diseases such as drug addiction. Previously, we developed a multimodal-imaging platform (OFI) which combined laser speckle contrast imaging with multi-wavelength imaging to simultaneously characterize the changes in cerebral blood flow (CBF), oxygenated- and deoxygenated- hemoglobin (HbO and HbR) from animal brain. Recently, we upgraded our OFI system that enables detection of hemodynamic changes in response to forepaw electrical stimulation to study potential brain activity changes elicited by cocaine. The improvement includes 1) high sensitivity to detect the cortical response to single forepaw electrical stimulation; 2) high temporal resolution (i.e., 16Hz/channel) to resolve dynamic variations in drug-delivery study; 3) high spatial resolution to separate the stimulation-evoked hemodynamic changes in vascular compartments from those in tissue. The system was validated by imaging the hemodynamic responses to the forepaw-stimulations in the somatosensory cortex of cocaine-treated rats. The stimulations and acquisitions were conducted every 2min over 40min, i.e., from 10min before (baseline) to 30min after cocaine challenge. Our results show that the HbO response decreased first (at ~4min) followed by the decrease of HbR response (at ~6min) after cocaine, and both did not fully recovered for over 30min. Interestingly, while CBF decreased at 4min, it partially recovered at 18min after cocaine administration. The results indicate the heterogeneity of cocaine's effects on vasculature and tissue metabolism, demonstrating the unique capability of optical imaging for brain functional studies.

Cholinergic modulation of visual and attentional brain responses in Alzheimer's disease and in health

PubMed Central

Bentley, P.; Driver, J.; Dolan, R.J.

2008-01-01

Visuo-attentional deficits occur early in Alzheimer's disease (AD) and are considered more responsive to pro-cholinergic therapy than characteristic memory disturbances. We hypothesised that neural responses in AD during visual attentional processing would be impaired relative to controls, yet partially susceptible to improvement with cholinesterase inhibition. We studied 16 mild AD patients and 17 age-matched healthy controls, using fMRI-scanning to enable within-subject placebo-controlled comparisons of the effects of physostigmine on stimulus- and attention-related brain activations, and to allow between-group comparisons for these. Subjects viewed stimuli comprising faces or buildings while performing a shallow judgement (colour of image) or a deep judgement (young/old age of depicted face or building). Behaviourally, AD subjects performed poorer than controls in both tasks, while physostigmine benefited AD patients for the more demanding age-judgement task. Stimulus-selective (face minus building, and vice versa) BOLD signals in precuneus and posterior parahippocampal cortex were attenuated in AD relative to controls but increased following physostigmine. By contrast, face-selective responses in fusiform cortex were not impaired in AD and showed decreases following physostigmine for both groups. Task-dependent responses in right parietal and prefrontal cortices were diminished in AD but improved following physostigmine. A similar pattern of group and treatment effects was observed in two extrastriate cortical regions that showed enhanced stimulus-selectivity for the deep versus shallow task. Finally, for the healthy group, physostigmine decreased task-dependent effects, partly due to an exaggeration of selectivity during the shallow relative to deep task. Our results demonstrate cholinergic-mediated improvements for both stimulus- and attention-dependent responses in functionally affected extrastriate and frontoparietal regions for AD. We also show that normal

Functional Topography of Early Periventricular Brain Lesions in Relation to Cytoarchitectonic Probabilistic Maps

ERIC Educational Resources Information Center

Staudt, Martin; Ticini, Luca F.; Grodd, Wolfgang; Krageloh-Mann, Ingeborg; Karnath, Hans-Otto

2008-01-01

Early periventricular brain lesions can not only cause cerebral palsy, but can also induce a reorganization of language. Here, we asked whether these different functional consequences can be attributed to topographically distinct portions of the periventricular white matter damage. Eight patients with pre- and perinatally acquired left-sided…

Early Human Speciation, Brain Expansion and Dispersal Influenced by African Climate Pulses

PubMed Central

Shultz, Susanne; Maslin, Mark

2013-01-01

Early human evolution is characterised by pulsed speciation and dispersal events that cannot be explained fully by global or continental paleoclimate records. We propose that the collated record of ephemeral East African Rift System (EARS) lakes could be a proxy for the regional paleoclimate conditions experienced by early hominins. Here we show that the presence of these lakes is associated with low levels of dust deposition in both West African and Mediterranean records, but is not associated with long-term global cooling and aridification of East Africa. Hominin expansion and diversification seem to be associated with climate pulses characterized by the precession-forced appearance and disappearance of deep EARS lakes. The most profound period for hominin evolution occurs at about 1.9 Ma; with the highest recorded diversity of hominin species, the appearance of Homo (sensu stricto) and major dispersal events out of East Africa into Eurasia. During this period, ephemeral deep-freshwater lakes appeared along the whole length of the EARS, fundamentally changing the local environment. The relationship between the local environment and hominin brain expansion is less clear. The major step-wise expansion in brain size around 1.9 Ma when Homo appeared was coeval with the occurrence of ephemeral deep lakes. Subsequent incremental increases in brain size are associated with dry periods with few if any lakes. Plio-Pleistocene East African climate pulses as evinced by the paleo-lake records seem, therefore, fundamental to hominin speciation, encephalisation and migration. PMID:24146922

Early human speciation, brain expansion and dispersal influenced by African climate pulses.

PubMed

Shultz, Susanne; Maslin, Mark

2013-01-01

Early human evolution is characterised by pulsed speciation and dispersal events that cannot be explained fully by global or continental paleoclimate records. We propose that the collated record of ephemeral East African Rift System (EARS) lakes could be a proxy for the regional paleoclimate conditions experienced by early hominins. Here we show that the presence of these lakes is associated with low levels of dust deposition in both West African and Mediterranean records, but is not associated with long-term global cooling and aridification of East Africa. Hominin expansion and diversification seem to be associated with climate pulses characterized by the precession-forced appearance and disappearance of deep EARS lakes. The most profound period for hominin evolution occurs at about 1.9 Ma; with the highest recorded diversity of hominin species, the appearance of Homo (sensu stricto) and major dispersal events out of East Africa into Eurasia. During this period, ephemeral deep-freshwater lakes appeared along the whole length of the EARS, fundamentally changing the local environment. The relationship between the local environment and hominin brain expansion is less clear. The major step-wise expansion in brain size around 1.9 Ma when Homo appeared was coeval with the occurrence of ephemeral deep lakes. Subsequent incremental increases in brain size are associated with dry periods with few if any lakes. Plio-Pleistocene East African climate pulses as evinced by the paleo-lake records seem, therefore, fundamental to hominin speciation, encephalisation and migration.

Finite element modeling of human brain response to football helmet impacts.

PubMed

Darling, T; Muthuswamy, J; Rajan, S D

2016-10-01

The football helmet is used to help mitigate the occurrence of impact-related traumatic (TBI) and minor traumatic brain injuries (mTBI) in the game of American football. While the current helmet design methodology may be adequate for reducing linear acceleration of the head and minimizing TBI, it however has had less effect in minimizing mTBI. The objectives of this study are (a) to develop and validate a coupled finite element (FE) model of a football helmet and the human body, and (b) to assess responses of different regions of the brain to two different impact conditions - frontal oblique and crown impact conditions. The FE helmet model was validated using experimental results of drop tests. Subsequently, the integrated helmet-human body FE model was used to assess the responses of different regions of the brain to impact loads. Strain-rate, strain, and stress measures in the corpus callosum, midbrain, and brain stem were assessed. Results show that maximum strain-rates of 27 and 19 s(-1) are observed in the brain-stem and mid-brain, respectively. This could potentially lead to axonal injuries and neuronal cell death during crown impact conditions. The developed experimental-numerical framework can be used in the study of other helmet-related impact conditions.

Early life influences on emotional reactivity: evidence that social enrichment has greater effects than handling on anxiety-like behaviors, neuroendocrine responses to stress and central BDNF levels.

PubMed

Cirulli, Francesca; Berry, Alessandra; Bonsignore, Luca Tommaso; Capone, Francesca; D'Andrea, Ivana; Aloe, Luigi; Branchi, Igor; Alleva, Enrico

2010-05-01

During the early post-natal phases the brain is experience-seeking and provided by a considerable plasticity which allows a fine tuning between the external environment and the developing organism. Since the early work of Seymour Levine, an impressive amount of research has clearly shown that stressful experiences exert powerful effects on the brain and body development. These effects can last throughout the entire life span influencing brain function and increasing the risk for depression and anxiety disorders. The mechanisms underlying the effects of early stress on the developing organism have been widely studied in rodents through experimental manipulations of the post-natal environment, such as handling, which have been shown to exert important effects on the emotional phenotype and the response to stress. In the present paper we review the relevant literature and present some original data indicating that, compared to handling, which imposes an external manipulation on the mother-infant relationship, social enrichment, in the form of communal rearing, in mice has very profound effects on animal's emotionality and the response to stress. These effects are also accompanied by important changes in central levels of brain-derived neurotrophic factor. The present data indicate that communal rearing has more pervasive effects than handling, strengthening previous data suggesting that it is a good animal model of reduced susceptibility to depression-like behavior. Overall, the availability of ever more sophisticated animal models represents a fundamental tool to translate basic research data into appropriate interventions for humans raised under traumatic or impoverished situations. (c) 2010 Elsevier Ltd. All rights reserved.

Brain Responses to High-Protein Diets12

PubMed Central

Journel, Marion; Chaumontet, Catherine; Darcel, Nicolas; Fromentin, Gilles; Tomé, Daniel

2012-01-01

Proteins are suspected to have a greater satiating effect than the other 2 macronutrients. After protein consumption, peptide hormones released from the gastrointestinal tract (mainly anorexigenic gut peptides such as cholecystokinin, glucagon peptide 1, and peptide YY) communicate information about the energy status to the brain. These hormones and vagal afferents control food intake by acting on brain regions involved in energy homeostasis such as the brainstem and the hypothalamus. In fact, a high-protein diet leads to greater activation than a normal-protein diet in the nucleus tractus solitarius and in the arcuate nucleus. More specifically, neural mechanisms triggered particularly by leucine consumption involve 2 cellular energy sensors: the mammalian target of rapamycin and AMP-activated protein kinase. In addition, reward and motivation aspects of eating behavior, controlled mainly by neurons present in limbic regions, play an important role in the reduced hedonic response of a high-protein diet. This review examines how metabolic signals emanating from the gastrointestinal tract after protein ingestion target the brain to control feeding, energy expenditure, and hormones. Understanding the functional roles of brain areas involved in the satiating effect of proteins and their interactions will demonstrate how homeostasis and reward are integrated with the signals from peripheral organs after protein consumption. PMID:22585905

Brain networks associated with cognitive and hedonic responses to a meal.

PubMed

Pribic, T; Kilpatrick, L; Ciccantelli, B; Malagelada, C; Accarino, A; Rovira, A; Pareto, D; Mayer, E; Azpiroz, F

2017-06-01

We recently reported interrelated digestive, cognitive, and hedonic responses to a meal. The aim of this study was to identify brain networks related to the hedonic response to eating. Thirty-eight healthy subjects (20-38 age range) were evaluated after a 5-hour fast and after ingestion of a test meal (juice and warm ham and cheese sandwich, 300 mL, 425 kcal). Perceptual and affective responses (satiety, abdominal fullness, digestive well-being, and positive mood), and resting scans of the brain using functional MRI (3T Trio, Siemens, Germany) were evaluated immediately before and after the test meal. A high-order group independent component analysis was performed to investigate ingestion-related changes in the intrinsic connectivity of brain networks, with a focus on thalamic and insular networks. Ingestion induced satiation (3.3±0.4 score increase; P<.001) and abdominal fullness (2.4±0.3 score increase; P<.001). These sensations included an affective dimension involving digestive well-being (2.8±0.3 score increase; P<.001) and positive mood (1.8±0.2 score increase; P<.001). In general, thalamo-cortical connectivity increased with meal ingestion while insular-cortical connectivity mainly decreased. Furthermore, larger meal-induced changes (increase/decrease) in specific thalamic connections were associated with smaller changes in satiety/fullness. In contrast, a larger meal-induced decrease in insular-anterior cingulate cortex connectivity was associated with increased satiety, fullness, and digestive well-being. Perceptual and emotional responses to food intake are related to brain connectivity in defined functional networks. Brain imaging may provide objective biomarkers of subjective effects of meal ingestion. © 2017 John Wiley & Sons Ltd.

Functional selectivity for face processing in the temporal voice area of early deaf individuals

PubMed Central

van Ackeren, Markus J.; Rabini, Giuseppe; Zonca, Joshua; Foa, Valentina; Baruffaldi, Francesca; Rezk, Mohamed; Pavani, Francesco; Rossion, Bruno; Collignon, Olivier

2017-01-01

Brain systems supporting face and voice processing both contribute to the extraction of important information for social interaction (e.g., person identity). How does the brain reorganize when one of these channels is absent? Here, we explore this question by combining behavioral and multimodal neuroimaging measures (magneto-encephalography and functional imaging) in a group of early deaf humans. We show enhanced selective neural response for faces and for individual face coding in a specific region of the auditory cortex that is typically specialized for voice perception in hearing individuals. In this region, selectivity to face signals emerges early in the visual processing hierarchy, shortly after typical face-selective responses in the ventral visual pathway. Functional and effective connectivity analyses suggest reorganization in long-range connections from early visual areas to the face-selective temporal area in individuals with early and profound deafness. Altogether, these observations demonstrate that regions that typically specialize for voice processing in the hearing brain preferentially reorganize for face processing in born-deaf people. Our results support the idea that cross-modal plasticity in the case of early sensory deprivation relates to the original functional specialization of the reorganized brain regions. PMID:28652333

A Coordinated Action of Blood-Borne and Brain Insulin-Like Growth Factor I in the Response to Traumatic Brain Injury.

PubMed

Santi, A; Genis, L; Torres Aleman, I

2018-06-01

In response to injury, the brain produces different neuroprotective molecules, such as insulin-like growth factor I (IGF-I). However, IGF-I is also taken up by the brain from the circulation in response to physiological stimuli. Herein, we analyzed in mice the relative contribution of circulating and locally produced IGF-I to increased brain IGF-I levels after insult. Traumatic brain injury (TBI) induced by a controlled impact resulted in increased IGF-I levels in the vicinity of the lesion, but mice with low serum IGF-I showed significantly lower increases. Indeed, in normal mice, peripheral IGF-I accumulated at the lesion site after injury, and at the same time serum IGF-I levels decreased. Collectively, these data suggest that serum IGF-I enter into the brain after TBI and contributes to increased brain IGF-I levels at the injury site. This connection between central and circulating IGF-I provides an amenable route for treatment, as subcutaneous administration of IGF-I to TBI mice led to functional recovery. These latter results add further support to the use of systemic IGF-I or its mimetics for treatment of brain injuries.

Early Oxygen-Utilization and Brain Activity in Preterm Infants

PubMed Central

de Vries, Linda S.; Groenendaal, Floris; Toet, Mona C.; Lemmers, Petra M. A.; Vosse van de, Renè E.; van Bel, Frank; Benders, Manon J. N. L.

2015-01-01

The combined monitoring of oxygen supply and delivery using Near-InfraRed spectroscopy (NIRS) and cerebral activity using amplitude-integrated EEG (aEEG) could yield new insights into brain metabolism and detect potentially vulnerable conditions soon after birth. The relationship between NIRS and quantitative aEEG/EEG parameters has not yet been investigated. Our aim was to study the association between oxygen utilization during the first 6 h after birth and simultaneously continuously monitored brain activity measured by aEEG/EEG. Forty-four hemodynamically stable babies with a GA < 28 weeks, with good quality NIRS and aEEG/EEG data available and who did not receive morphine were included in the study. aEEG and NIRS monitoring started at NICU admission. The relation between regional cerebral oxygen saturation (rScO2) and cerebral fractional tissue oxygen extraction (cFTOE), and quantitative measurements of brain activity such as number of spontaneous activity transients (SAT) per minute (SAT rate), the interval in seconds (i.e. time) between SATs (ISI) and the minimum amplitude of the EEG in μV (min aEEG) were evaluated. rScO2 was negatively associated with SAT rate (β=-3.45 [CI=-5.76- -1.15], p=0.004) and positively associated with ISI (β=1.45 [CI=0.44-2.45], p=0.006). cFTOE was positively associated with SAT rate (β=0.034 [CI=0.009-0.059], p=0.008) and negatively associated with ISI (β=-0.015 [CI=-0.026- -0.004], p=0.007). Oxygen delivery and utilization, as indicated by rScO2 and cFTOE, are directly related to functional brain activity, expressed by SAT rate and ISI during the first hours after birth, showing an increase in oxygen extraction in preterm infants with increased early electro-cerebral activity. NIRS monitored oxygenation may be a useful biomarker of brain vulnerability in high-risk infants. PMID:25965343

Brain atrophy can introduce age-related differences in BOLD response.

PubMed

Liu, Xueqing; Gerraty, Raphael T; Grinband, Jack; Parker, David; Razlighi, Qolamreza R

2017-04-11

Use of functional magnetic resonance imaging (fMRI) in studies of aging is often hampered by uncertainty about age-related differences in the amplitude and timing of the blood oxygenation level dependent (BOLD) response (i.e., hemodynamic impulse response function (HRF)). Such uncertainty introduces a significant challenge in the interpretation of the fMRI results. Even though this issue has been extensively investigated in the field of neuroimaging, there is currently no consensus about the existence and potential sources of age-related hemodynamic alterations. Using an event-related fMRI experiment with two robust and well-studied stimuli (visual and auditory), we detected a significant age-related difference in the amplitude of response to auditory stimulus. Accounting for brain atrophy by circumventing spatial normalization and processing the data in subjects' native space eliminated these observed differences. In addition, we simulated fMRI data using age differences in brain morphology while controlling HRF shape. Analyzing these simulated fMRI data using standard image processing resulted in differences in HRF amplitude, which were eliminated when the data were analyzed in subjects' native space. Our results indicate that age-related atrophy introduces inaccuracy in co-registration to standard space, which subsequently appears as attenuation in BOLD response amplitude. Our finding could explain some of the existing contradictory reports regarding age-related differences in the fMRI BOLD responses. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Early embryonic brain development in rats requires the trophic influence of cerebrospinal fluid.

PubMed

Martin, C; Alonso, M I; Santiago, C; Moro, J A; De la Mano, A; Carretero, R; Gato, A

2009-11-01

Cerebrospinal fluid has shown itself to be an essential brain component during development. This is particularly evident at the earliest stages of development where a lot of research, performed mainly in chick embryos, supports the evidence that cerebrospinal fluid is involved in different mechanisms controlling brain growth and morphogenesis, by exerting a trophic effect on neuroepithelial precursor cells (NPC) involved in controlling the behaviour of these cells. Despite it being known that cerebrospinal fluid in mammals is directly involved in corticogenesis at fetal stages, the influence of cerebrospinal fluid on the activity of NPC at the earliest stages of brain development has not been demonstrated. Here, using "in vitro" organotypic cultures of rat embryo brain neuroepithelium in order to expose NPC to or deprive them of cerebrospinal fluid, we show that the neuroepithelium needs the trophic influence of cerebrospinal fluid to undergo normal rates of cell survival, replication and neurogenesis, suggesting that NPC are not self-sufficient to induce their normal activity. This data shows that cerebrospinal fluid is an essential component in chick and rat early brain development, suggesting that its influence could be constant in higher vertebrates.

Early life predictors of brain development at term-equivalent age in infants born across the gestational age spectrum.

PubMed

Thompson, Deanne K; Kelly, Claire E; Chen, Jian; Beare, Richard; Alexander, Bonnie; Seal, Marc L; Lee, Katherine; Matthews, Lillian G; Anderson, Peter J; Doyle, Lex W; Spittle, Alicia J; Cheong, Jeanie L Y

2018-04-13

It is well established that preterm infants have altered brain development compared with full-term (FT; ≥37 weeks' gestational age [GA]) infants, however the perinatal factors associated with brain development in preterm infants have not been fully elucidated. In particular, perinatal predictors of brain development may differ between very preterm infants (VP; <32 weeks' GA) and infants born moderate (MP; 32-33 weeks' GA) and late (LP; 34-36 weeks' GA) preterm, but this has not been studied. This study aimed to investigate the effects of early life predictors on brain volume and microstructure at term-equivalent age (TEA; 38-44 weeks), and whether these effects differ for GA groups (VP, MP, LP or FT). Structural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid, subcortical grey matter, brainstem and cerebellum. Cortical grey matter and white matter images were analysed using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Relationships between early life predictors (birthweight standard deviation score [BWSDS], multiple birth, sex, postnatal growth and social risk) and global brain volumes were analysed using linear regressions. Relationships between early life predictors and regional brain volumes and diffusion measures were analysed using voxelwise non-parametric permutation testing. Male sex was associated with higher global volumes of all tissues and higher regional volumes throughout much of the cortical grey matter and white matter, particularly in the FT group. Male sex was also associated with lower FA and higher AD, RD and MD in the optic radiation, external and internal capsules and corona radiata, and these associations were generally similar between GA groups. Higher BWSDS was

Brain network informed subject community detection in early-onset schizophrenia.

PubMed

Yang, Zhi; Xu, Yong; Xu, Ting; Hoy, Colin W; Handwerker, Daniel A; Chen, Gang; Northoff, Georg; Zuo, Xi-Nian; Bandettini, Peter A

2014-07-03

Early-onset schizophrenia (EOS) offers a unique opportunity to study pathophysiological mechanisms and development of schizophrenia. Using 26 drug-naïve, first-episode EOS patients and 25 age- and gender-matched control subjects, we examined intrinsic connectivity network (ICN) deficits underlying EOS. Due to the emerging inconsistency between behavior-based psychiatric disease classification system and the underlying brain dysfunctions, we applied a fully data-driven approach to investigate whether the subjects can be grouped into highly homogeneous communities according to the characteristics of their ICNs. The resultant subject communities and the representative characteristics of ICNs were then associated with the clinical diagnosis and multivariate symptom patterns. A default mode ICN was statistically absent in EOS patients. Another frontotemporal ICN further distinguished EOS patients with predominantly negative symptoms. Connectivity patterns of this second network for the EOS patients with predominantly positive symptom were highly similar to typically developing controls. Our post-hoc functional connectivity modeling confirmed that connectivity strength in this frontotemporal circuit was significantly modulated by relative severity of positive and negative syndromes in EOS. This study presents a novel subtype discovery approach based on brain networks and proposes complex links between brain networks and symptom patterns in EOS.

New perspectives on central and peripheral immune responses to acute traumatic brain injury

PubMed Central

2012-01-01

Traumatic injury to the brain (TBI) results in a complex set of responses involving various symptoms and long-term consequences. TBI of any form can cause cognitive, behavioral and immunologic changes in later life, which underscores the problem of underdiagnosis of mild TBI that can cause long-term neurological deficits. TBI disrupts the blood–brain barrier (BBB) leading to infiltration of immune cells into the brain and subsequent inflammation and neurodegeneration. TBI-induced peripheral immune responses can also result in multiorgan damage. Despite worldwide research efforts, the methods of diagnosis, monitoring and treatment for TBI are still relatively ineffective. In this review, we delve into the mechanism of how TBI-induced central and peripheral immune responses affect the disease outcome and discuss recent developments in the continuing effort to combat the consequences of TBI and new ways to enhance repair of the damaged brain. PMID:23061919

Brain stem auditory evoked responses in human infants and adults

NASA Technical Reports Server (NTRS)

Hecox, K.; Galambos, R.

1974-01-01

Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

Localization of MEG human brain responses to retinotopic visual stimuli with contrasting source reconstruction approaches

PubMed Central

Cicmil, Nela; Bridge, Holly; Parker, Andrew J.; Woolrich, Mark W.; Krug, Kristine

2014-01-01

Magnetoencephalography (MEG) allows the physiological recording of human brain activity at high temporal resolution. However, spatial localization of the source of the MEG signal is an ill-posed problem as the signal alone cannot constrain a unique solution and additional prior assumptions must be enforced. An adequate source reconstruction method for investigating the human visual system should place the sources of early visual activity in known locations in the occipital cortex. We localized sources of retinotopic MEG signals from the human brain with contrasting reconstruction approaches (minimum norm, multiple sparse priors, and beamformer) and compared these to the visual retinotopic map obtained with fMRI in the same individuals. When reconstructing brain responses to visual stimuli that differed by angular position, we found reliable localization to the appropriate retinotopic visual field quadrant by a minimum norm approach and by beamforming. Retinotopic map eccentricity in accordance with the fMRI map could not consistently be localized using an annular stimulus with any reconstruction method, but confining eccentricity stimuli to one visual field quadrant resulted in significant improvement with the minimum norm. These results inform the application of source analysis approaches for future MEG studies of the visual system, and indicate some current limits on localization accuracy of MEG signals. PMID:24904268

Outlier Responses Reflect Sensitivity to Statistical Structure in the Human Brain

PubMed Central

Garrido, Marta I.

2013-01-01

We constantly look for patterns in the environment that allow us to learn its key regularities. These regularities are fundamental in enabling us to make predictions about what is likely to happen next. The physiological study of regularity extraction has focused primarily on repetitive sequence-based rules within the sensory environment, or on stimulus-outcome associations in the context of reward-based decision-making. Here we ask whether we implicitly encode non-sequential stochastic regularities, and detect violations therein. We addressed this question using a novel experimental design and both behavioural and magnetoencephalographic (MEG) metrics associated with responses to pure-tone sounds with frequencies sampled from a Gaussian distribution. We observed that sounds in the tail of the distribution evoked a larger response than those that fell at the centre. This response resembled the mismatch negativity (MMN) evoked by surprising or unlikely events in traditional oddball paradigms. Crucially, responses to physically identical outliers were greater when the distribution was narrower. These results show that humans implicitly keep track of the uncertainty induced by apparently random distributions of sensory events. Source reconstruction suggested that the statistical-context-sensitive responses arose in a temporo-parietal network, areas that have been associated with attention orientation to unexpected events. Our results demonstrate a very early neurophysiological marker of the brain's ability to implicitly encode complex statistical structure in the environment. We suggest that this sensitivity provides a computational basis for our ability to make perceptual inferences in noisy environments and to make decisions in an uncertain world. PMID:23555230

Neurotechnology and Society: Strengthening Responsible Innovation in Brain Science.

PubMed

Garden, Hermann; Bowman, Diana M; Haesler, Sebastian; Winickoff, David E

2016-11-02

Technological advances have the potential to dramatically increase our understanding of the human brain, treat and cure injury and disease, and enhance our general well-being. While advances in neuroscience hold great promise, they also raise profound ethical, legal, and social questions. In this vein, the Organization for Economic Co-operation and Development (OECD) convened an international workshop in September 2016 to explore responsible research and innovation in brain science. Copyright © 2016 OECD. Published by Elsevier Inc. All rights reserved.

Predation risk modifies behaviour by shaping the response of identified brain neurons.

PubMed

Magani, Fiorella; Luppi, Tomas; Nuñez, Jesus; Tomsic, Daniel

2016-04-15

Interpopulation comparisons in species that show behavioural variations associated with particular ecological disparities offer good opportunities for assessing how environmental factors may foster specific functional adaptations in the brain. Yet, studies on the neural substrate that can account for interpopulation behavioural adaptations are scarce. Predation is one of the strongest driving forces for behavioural evolvability and, consequently, for shaping structural and functional brain adaptations. We analysed the escape response of crabs ITALIC! Neohelice granulatafrom two isolated populations exposed to different risks of avian predation. Individuals from the high-risk area proved to be more reactive to visual danger stimuli (VDS) than those from an area where predators are rare. Control experiments indicate that the response difference was specific for impending visual threats. Subsequently, we analysed the response to VDS of a group of giant brain neurons that are thought to play a main role in the visually guided escape response of the crab. Neurons from animals of the population with the stronger escape response were more responsive to VDS than neurons from animals of the less reactive population. Our results suggest a robust linkage between the pressure imposed by the predation risk, the response of identified neurons and the behavioural outcome. © 2016. Published by The Company of Biologists Ltd.

Activation of Brain Somatostatin Signaling Suppresses CRF Receptor-Mediated Stress Response.

PubMed

Stengel, Andreas; Taché, Yvette F

2017-01-01

Corticotropin-releasing factor (CRF) is the hallmark brain peptide triggering the response to stress and mediates-in addition to the stimulation of the hypothalamus-pituitary-adrenal (HPA) axis-other hormonal, behavioral, autonomic and visceral components. Earlier reports indicate that somatostatin-28 injected intracerebroventricularly counteracts the acute stress-induced ACTH and catecholamine release. Mounting evidence now supports that activation of brain somatostatin signaling exerts a broader anti-stress effect by blunting the endocrine, autonomic, behavioral (with a focus on food intake) and visceral gastrointestinal motor responses through the involvement of distinct somatostatin receptor subtypes.

Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence.

PubMed

Guyer, Amanda E; Jarcho, Johanna M; Pérez-Edgar, Koraly; Degnan, Kathryn A; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

2015-07-01

Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children's caregiving context. The convergence of a child's temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (M(age) = 17.89 years, N = 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development.

Temperament and Parenting Styles in Early Childhood Differentially Influence Neural Response to Peer Evaluation in Adolescence

PubMed Central

Guyer, Amanda E.; Jarcho, Johanna M.; Pérez-Edgar, Koraly; Degnan, Kathryn A.; Pine, Daniel S.; Fox, Nathan A.; Nelson, Eric E.

2015-01-01

Behavioral inhibition (BI) is a temperament characterized by social reticence and withdrawal from unfamiliar or novel contexts and conveys risk for social anxiety disorder. Developmental outcomes associated with this temperament can be influenced by children’s caregiving context. The convergence of a child’s temperamental disposition and rearing environment is ultimately expressed at both the behavioral and neural levels in emotional and cognitive response patterns to social challenges. The present study used functional neuroimaging to assess the moderating effects of different parenting styles on neural response to peer rejection in two groups of adolescents characterized by their early childhood temperament (Mage = 17.89 years, N= 39, 17 males, 22 females; 18 with BI; 21 without BI). The moderating effects of authoritarian and authoritative parenting styles were examined in three brain regions linked with social anxiety: ventrolateral prefrontal cortex (vlPFC), striatum, and amygdala. In youth characterized with BI in childhood, but not in those without BI, diminished responses to peer rejection in vlPFC were associated with higher levels of authoritarian parenting. In contrast, all youth showed decreased caudate response to peer rejection at higher levels of authoritative parenting. These findings indicate that BI in early life relates to greater neurobiological sensitivity to variance in parenting styles, particularly harsh parenting, in late adolescence. These results are discussed in relation to biopsychosocial models of development. PMID:25588884

A role for neuronal cAMP responsive-element binding (CREB)-1 in brain responses to calorie restriction

PubMed Central

Fusco, Salvatore; Ripoli, Cristian; Podda, Maria Vittoria; Ranieri, Sofia Chiatamone; Leone, Lucia; Toietta, Gabriele; McBurney, Michael W.; Schütz, Günther; Riccio, Antonella; Grassi, Claudio; Galeotti, Tommaso; Pani, Giovambattista

2012-01-01

Calorie restriction delays brain senescence and prevents neurodegeneration, but critical regulators of these beneficial responses other than the NAD+-dependent histone deacetylase Sirtuin-1 (Sirt-1) are unknown. We report that effects of calorie restriction on neuronal plasticity, memory and social behavior are abolished in mice lacking cAMP responsive-element binding (CREB)-1 in the forebrain. Moreover, CREB deficiency drastically reduces the expression of Sirt-1 and the induction of genes relevant to neuronal metabolism and survival in the cortex and hippocampus of dietary-restricted animals. Biochemical studies reveal a complex interplay between CREB and Sirt-1: CREB directly regulates the transcription of the sirtuin in neuronal cells by binding to Sirt-1 chromatin; Sirt-1, in turn, is recruited by CREB to DNA and promotes CREB-dependent expression of target gene peroxisome proliferator-activated receptor-γ coactivator-1α and neuronal NO Synthase. Accordingly, expression of these CREB targets is markedly reduced in the brain of Sirt KO mice that are, like CREB-deficient mice, poorly responsive to calorie restriction. Thus, the above circuitry, modulated by nutrient availability, links energy metabolism with neurotrophin signaling, participates in brain adaptation to nutrient restriction, and is potentially relevant to accelerated brain aging by overnutrition and diabetes. PMID:22190495

Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

PubMed

Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

2012-01-01

Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

DAT Genotype Modulates Brain and Behavioral Responses Elicited by Cigarette Cues

PubMed Central

Franklin, Teresa R; Lohoff, Falk W; Wang, Ze; Sciortino, Nathan; Harper, Derek; Li, Yin; Jens, Will; Cruz, Jeffrey; Kampman, Kyle; Ehrman, Ron; Berrettini, Wade; Detre, John A; O'Brien, Charles P; Childress, Anna Rose

2011-01-01

We previously demonstrated differential activation of the mesocorticolimbic reward circuitry in response to cigarette cues independent of withdrawal. Despite robust effects, we noted considerable individual variability in brain and subjective responses. As dopamine (DA) is critical for reward and its predictive signals, genetically driven variation in DA transmission may account for the observed differences. Evidence suggests that a variable number of tandem repeats (VNTRs) polymorphism in the DA transporter (DAT) SLC6A3 gene may influence DA transport. Brain and behavioral responses may be enhanced in probands carrying the 9-repeat allele. To test this hypothesis, perfusion fMR images were acquired during cue exposure in 19 smokers genotyped for the 40 bp VNTR polymorphism in the SLC6A3 gene. Contrasts between groups revealed that 9-repeat (9-repeats) had a greater response to smoking (vs nonsmoking) cues than smokers homozygous for the 10-repeat allele (10/10-repeats) bilaterally in the interconnected ventral striatal/pallidal/orbitofrontal cortex regions (VS/VP/OFC). Activity was increased in 9-repeats and decreased in 10/10-repeats in the VS/VP/OFC (p<0.001 for all analyses). Brain activity and craving was strongly correlated in 10/10-repeats in these regions and others (anterior cingulate, parahippocampal gyrus, and insula; r2 = 0.79–0.86, p<0.001 in all regions). Alternatively, there were no significant correlations between brain and behavior in 9-repeats. There were no differences in cigarette dependence, demographics, or resting baseline neural activity between groups. These results provide evidence that genetic variation in the DAT gene contributes to the neural and behavioral responses elicited by smoking cues. PMID:18704100

Simulation of blast-induced early-time intracranial wave physics leading to traumatic brain injury.

PubMed

Taylor, Paul A; Ford, Corey C

2009-06-01

The objective of this modeling and simulation study was to establish the role of stress wave interactions in the genesis of traumatic brain injury (TBI) from exposure to explosive blast. A high resolution (1 mm3 voxels) five material model of the human head was created by segmentation of color cryosections from the Visible Human Female data set. Tissue material properties were assigned from literature values. The model was inserted into the shock physics wave code, CTH, and subjected to a simulated blast wave of 1.3 MPa (13 bars) peak pressure from anterior, posterior, and lateral directions. Three-dimensional plots of maximum pressure, volumetric tension, and deviatoric (shear) stress demonstrated significant differences related to the incident blast geometry. In particular, the calculations revealed focal brain regions of elevated pressure and deviatoric stress within the first 2 ms of blast exposure. Calculated maximum levels of 15 KPa deviatoric, 3.3 MPa pressure, and 0.8 MPa volumetric tension were observed before the onset of significant head accelerations. Over a 2 ms time course, the head model moved only 1 mm in response to the blast loading. Doubling the blast strength changed the resulting intracranial stress magnitudes but not their distribution. We conclude that stress localization, due to early-time wave interactions, may contribute to the development of multifocal axonal injury underlying TBI. We propose that a contribution to traumatic brain injury from blast exposure, and most likely blunt impact, can occur on a time scale shorter than previous model predictions and before the onset of linear or rotational accelerations traditionally associated with the development of TBI.

Effects of Early Life Stress on Depression, Cognitive Performance, and Brain Morphology

PubMed Central

Saleh, Ayman; Potter, Guy G.; McQuoid, Douglas R.; Boyd, Brian; Turner, Rachel; MacFall, James R; Taylor, Warren D.

2016-01-01

Background Childhood early life stress (ELS) increases risk of adulthood Major Depressive Disorder (MDD) and is associated with altered brain structure and function. It is unclear whether specific ELSs affect depression risk, cognitive function and brain structure. Methods This cross-sectional study included 64 antidepressant-free depressed and 65 never depressed individuals. Both groups reported a range of ELSs on the Early Life Stress Questionnaire, completed neuropsychological testing and 3T MRI. Neuropsychological testing assessed domains of episodic memory, working memory, processing speed and executive function. MRI measures included cortical thickness and regional gray matter volumes, with a priori focus on cingulate cortex, orbitofrontal cortex (OFC), amygdala, caudate and hippocampus. Results Of 19 ELSs, only emotional abuse, sexual abuse and severe family conflict independently predicted adulthood MDD diagnosis. The effect of total ELS score differed between groups. Greater ELS exposure was associated with slower processing speed and smaller OFC volumes in depressed subjects, but faster speed and larger volumes in nondepressed subjects. In contrast, exposure to ELSs predictive of depression had similar effects in both diagnostic groups. Individuals reporting predictive ELSs exhibited poorer processing speed and working memory performance, smaller volumes of the lateral OFC and caudate, and decreased cortical thickness in multiple areas including the insula bilaterally. Predictive ELS exposure was also associated with smaller left hippocampal volume in depressed subjects. Conclusion Findings suggest an association between childhood trauma exposure and adulthood cognitive function and brain structure. These relationships appear to differ between individuals who do and do not develop depression. PMID:27682320

Effects of Early Serotonin Programming on Fear Response, Memory and Aggression

USDA-ARS?s Scientific Manuscript database

The neurotransmitter serotonin (5-HT) also acts as a neurogenic compound in the developing brain. Early administration of a 5-HT agonist could alter development of serotonergic circuitry, altering behaviors mediated by 5-HT signaling, including memory, fear and aggression. The present study was desi...

Predictive value of early brain atrophy on response in patients treated with interferon β

PubMed Central

Pérez-Miralles, Francisco Carlos; Vidal-Jordana, Angela; Río, Jordi; Auger, Cristina; Pareto, Deborah; Tintoré, Mar; Rovira, Alex; Montalban, Xavier

2015-01-01

Objective: To investigate the association between brain volume loss during the first year of interferon treatment and clinical outcome at 4 years. Methods: Patients with multiple sclerosis initiating interferon β were clinically evaluated every 6 months for the presence of relapses and assessment of global disability using the Expanded Disability Status Scale (EDSS). MRI scans were performed at baseline and after 12 months, and the percentage of brain volume change (PBVC), brain parenchymal volume change (BPVc%), gray matter volume change (GMVc%), and white matter volume change (WMVc%) were estimated. Patients were divided based on the cutoff values for predicting confirmed EDSS worsening obtained by receiver operating characteristic analysis for all atrophy measurements. Survival curves and Cox proportional hazards regression to predict disability worsening at last observation were applied, adjusting for demographic, clinical, and radiologic variables. Results: Larger PBVC and WMVc% decreases were observed in patients with disability worsening at 4 years of follow-up, whereas no differences were found in BPVc% or GMVc%. Cutoff points were obtained for PBVC (−0.86%; sensitivity 65.5%, specificity 71.4%) and WMVc% (−2.49%; sensitivity 85.3%, specificity 43.8%). Patients with decreases of PBVC and WMVc% below cutoff values were more prone to develop disability worsening (unadjusted hazard ratio [HR] 3.875, p = 0.005; HR 4.246, p = 0.004, respectively). PBVC (HR 4.751, p = 0.008) and the interaction of new T2 lesions with WMVc% (HR 1.086, p = 0.005) were found to be independent predictors of disability worsening in the multivariate analysis. Conclusions: At the patient level, whole-brain and white matter volume changes in the first year of interferon β therapy are predictive of subsequent clinical evolution under treatment. PMID:26185778

Predictive value of early brain atrophy on response in patients treated with interferon β.

PubMed

Pérez-Miralles, Francisco Carlos; Sastre-Garriga, Jaume; Vidal-Jordana, Angela; Río, Jordi; Auger, Cristina; Pareto, Deborah; Tintoré, Mar; Rovira, Alex; Montalban, Xavier

2015-08-01

To investigate the association between brain volume loss during the first year of interferon treatment and clinical outcome at 4 years. Patients with multiple sclerosis initiating interferon β were clinically evaluated every 6 months for the presence of relapses and assessment of global disability using the Expanded Disability Status Scale (EDSS). MRI scans were performed at baseline and after 12 months, and the percentage of brain volume change (PBVC), brain parenchymal volume change (BPVc%), gray matter volume change (GMVc%), and white matter volume change (WMVc%) were estimated. Patients were divided based on the cutoff values for predicting confirmed EDSS worsening obtained by receiver operating characteristic analysis for all atrophy measurements. Survival curves and Cox proportional hazards regression to predict disability worsening at last observation were applied, adjusting for demographic, clinical, and radiologic variables. Larger PBVC and WMVc% decreases were observed in patients with disability worsening at 4 years of follow-up, whereas no differences were found in BPVc% or GMVc%. Cutoff points were obtained for PBVC (-0.86%; sensitivity 65.5%, specificity 71.4%) and WMVc% (-2.49%; sensitivity 85.3%, specificity 43.8%). Patients with decreases of PBVC and WMVc% below cutoff values were more prone to develop disability worsening (unadjusted hazard ratio [HR] 3.875, p = 0.005; HR 4.246, p = 0.004, respectively). PBVC (HR 4.751, p = 0.008) and the interaction of new T2 lesions with WMVc% (HR 1.086, p = 0.005) were found to be independent predictors of disability worsening in the multivariate analysis. At the patient level, whole-brain and white matter volume changes in the first year of interferon β therapy are predictive of subsequent clinical evolution under treatment.

Prolonged maternal separation attenuates BDNF-ERK signaling correlated with spine formation in the hippocampus during early brain development.

PubMed

Ohta, Ken-Ichi; Suzuki, Shingo; Warita, Katsuhiko; Kaji, Tomohiro; Kusaka, Takashi; Miki, Takanori

2017-04-01

Maternal separation (MS) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS, and focused on brain-derived neurotrophic factor (BDNF) as key factor because BDNF signaling has an essential role in synapse formation during early brain development. Using rat offspring exposed to MS for 6 h/day during postnatal days (PD) 2-20, we estimated BDNF signaling in the hippocampus during brain development. Our results show that MS attenuated BDNF expression and activation of extracellular signal-regulated kinase (ERK) around PD 7. Moreover, plasticity-related immediate early genes, which are transcriptionally regulated by BDNF-ERK signaling, were also reduced by MS around PD 7. Interestingly, detailed analysis revealed that MS particularly reduced expression of BDNF gene and immediate early genes in the cornu ammonis 1 (CA1) of hippocampus at PD 7. Considering that BDNF-ERK signaling is involved in spine formation, we next evaluated spine formation in the hippocampus during the weaning period. Our results show that MS particularly reduced mature spine density in proximal apical dendrites of CA1 pyramidal neurons at PD 21. These results suggest that MS could attenuate BDNF-ERK signaling during primary synaptogenesis with a region-specific manner, which is likely to lead to decreased spine formation and maturation observed in the hippocampal CA1 region. It is speculated that this incomplete spine formation during early brain development has an influence on learning capabilities throughout adulthood. © 2017 International Society for Neurochemistry.

The shopping brain: math anxiety modulates brain responses to buying decisions.

PubMed

Jones, William J; Childers, Terry L; Jiang, Yang

2012-01-01

Metacognitive theories propose that consumers track fluency feelings when buying, which may have biological underpinnings. We explored this using event-related potential (ERP) measures as twenty high-math anxiety (High MA) and nineteen low-math anxiety (Low MA) consumers made buying decisions for promoted (e.g., 15% discount) and non-promoted products. When evaluating prices, ERP correlates of higher perceptual and conceptual fluency were associated with buys, however only for High MA females under no promotions. In contrast, High MA females and Low MA males demonstrated greater FN400 amplitude, associated with enhanced conceptual processing, to prices of buys relative to non-buys under promotions. Concurrent late positive component (LPC) differences under no promotions suggest discrepant retrieval processes during price evaluations between consumer groups. When making decisions to buy or not, larger (smaller) P3, sensitive to outcome responses in the brain, was associated with buying for High MA females (Low MA females) under promotions, an effect also present for males under no promotions. Thus, P3 indexed decisions to buy differently between anxiety groups, but only for promoted items among females and for no promotions among males. Our findings indicate that perceptual and conceptual processes interact with anxiety and gender to modulate brain responses during consumer choices. Copyright © 2011 Elsevier B.V. All rights reserved.

Intravenous Heroin Induces Rapid Brain Hypoxia and Hyperglycemia that Precede Brain Metabolic Response.

PubMed

Solis, Ernesto; Cameron-Burr, Keaton T; Shaham, Yavin; Kiyatkin, Eugene A

2017-01-01

Heroin use and overdose have increased in recent years as people transition from abusing prescription opiates to using the cheaper street drug. Despite a long history of research, many physiological effects of heroin and their underlying mechanisms remain unknown. Here, we used high-speed amperometry to examine the effects of intravenous heroin on oxygen and glucose levels in the nucleus accumbens (NAc) in freely-moving rats. Heroin within the dose range of human drug use and rat self-administration (100-200 μg/kg) induced a rapid, strong, but transient drop in NAc oxygen that was followed by a slower and more prolonged rise in glucose. Using oxygen recordings in the subcutaneous space, a densely-vascularized site with no metabolic activity, we confirmed that heroin-induced brain hypoxia results from decreased blood oxygen, presumably due to drug-induced respiratory depression. Respiratory depression and the associated rise in CO 2 levels appear to drive tonic increases in NAc glucose via local vasodilation. Heroin-induced changes in oxygen and glucose were rapid and preceded the slow and prolonged increase in brain temperature and were independent of enhanced intra-brain heat production, an index of metabolic activation. A very high heroin dose (3.2 mg/kg), corresponding to doses used by experienced drug users in overdose conditions, caused strong and prolonged brain hypoxia and hyperglycemia coupled with robust initial hypothermia that preceded an extended hyperthermic response. Our data suggest heroin-induced respiratory depression as a trigger for brain hypoxia, which leads to hyperglycemia, both of which appear independent of subsequent changes in brain temperature and metabolic neural activity.

Intravenous Heroin Induces Rapid Brain Hypoxia and Hyperglycemia that Precede Brain Metabolic Response

PubMed Central

Cameron-Burr, Keaton T.; Shaham, Yavin

2017-01-01

Heroin use and overdose have increased in recent years as people transition from abusing prescription opiates to using the cheaper street drug. Despite a long history of research, many physiological effects of heroin and their underlying mechanisms remain unknown. Here, we used high-speed amperometry to examine the effects of intravenous heroin on oxygen and glucose levels in the nucleus accumbens (NAc) in freely-moving rats. Heroin within the dose range of human drug use and rat self-administration (100–200 μg/kg) induced a rapid, strong, but transient drop in NAc oxygen that was followed by a slower and more prolonged rise in glucose. Using oxygen recordings in the subcutaneous space, a densely-vascularized site with no metabolic activity, we confirmed that heroin-induced brain hypoxia results from decreased blood oxygen, presumably due to drug-induced respiratory depression. Respiratory depression and the associated rise in CO2 levels appear to drive tonic increases in NAc glucose via local vasodilation. Heroin-induced changes in oxygen and glucose were rapid and preceded the slow and prolonged increase in brain temperature and were independent of enhanced intra-brain heat production, an index of metabolic activation. A very high heroin dose (3.2 mg/kg), corresponding to doses used by experienced drug users in overdose conditions, caused strong and prolonged brain hypoxia and hyperglycemia coupled with robust initial hypothermia that preceded an extended hyperthermic response. Our data suggest heroin-induced respiratory depression as a trigger for brain hypoxia, which leads to hyperglycemia, both of which appear independent of subsequent changes in brain temperature and metabolic neural activity. PMID:28593192

Investigating the dynamics of the brain response to music: A central role of the ventral striatum/nucleus accumbens.

PubMed

Mueller, Karsten; Fritz, Thomas; Mildner, Toralf; Richter, Maxi; Schulze, Katrin; Lepsien, Jöran; Schroeter, Matthias L; Möller, Harald E

2015-08-01

Ventral striatal activity has been previously shown to correspond well to reward value mediated by music. Here, we investigate the dynamic brain response to music and manipulated counterparts using functional magnetic resonance imaging (fMRI). Counterparts of musical excerpts were produced by either manipulating the consonance/dissonance of the musical fragments or playing them backwards (or both). Results show a greater involvement of the ventral striatum/nucleus accumbens both when contrasting listening to music that is perceived as pleasant and listening to a manipulated version perceived as unpleasant (backward dissonant), as well as in a parametric analysis for increasing pleasantness. Notably, both analyses yielded a ventral striatal response that was strongest during an early phase of stimulus presentation. A hippocampal response to the musical stimuli was also observed, and was largely mediated by processing differences between listening to forward and backward music. This hippocampal involvement was again strongest during the early response to the music. Auditory cortex activity was more strongly evoked by the original (pleasant) music compared to its manipulated counterparts, but did not display a similar decline of activation over time as subcortical activity. These findings rather suggest that the ventral striatal/nucleus accumbens response during music listening is strongest in the first seconds and then declines. Copyright © 2015 Elsevier Inc. All rights reserved.

Increased temporal variability of striatum region facilitating the early antidepressant response in patients with major depressive disorder.

PubMed

Hou, Zhenghua; Kong, Youyong; He, Xiaofu; Yin, Yingying; Zhang, Yuqun; Yuan, Yonggui

2018-07-13

The aim of this study is to identify the difference of temporal variability among major depressive disorder (MDD) patients (with different early antidepressant responses) and healthy controls (HC), and further explore the relationship between pre-treatment temporal variability and early antidepressant response. At baseline, 77 treatment-naïve inpatients with MDD and 42 matched HC received clinical assessments and 3.0 Tesla resting-state functional magnetic resonance imaging scans. After 2 weeks' antidepressant treatment, the patients were subgrouped into responsive depression (RD, n = 40) and non-responding depression (NRD, n = 37) based on the reduction of Hamilton depression rating scale (HAMD). The temporal variability of 90 brain nodes was calculated for further analysis. Compared with the HC group, both the RD and NRD subjects showed greater baseline temporal variability (i.e., greater dynamic) in the left inferior occipital gyrus. Significantly greater temporal variability in the left pallidum was found in the RD group than the NRD and the HC groups, and the higher variability of left pallidum correlated positively with the HAMD reduction. Moreover, the pooled MDD (i.e., RD and NRD) group showed greater baseline temporal variability in the right inferior frontal gyrus, the left inferior occipital gyrus, the bilateral fusiform gyri and the left Heschl gyrus than the HC group. The distinctive pattern of dynamically reorganized networks may provide a crucial scaffold to facilitate early antidepressant response, and the temporal variability may serve as a promising indicator for the personalized therapy of MDD. Copyright © 2018 Elsevier Inc. All rights reserved.

Early endocrine alterations reflect prolonged stress and relate to 1-year functional outcome in patients with severe brain injury.

PubMed

Marina, Djordje; Klose, Marianne; Nordenbo, Annette; Liebach, Annette; Feldt-Rasmussen, Ulla

2015-06-01

Severe brain injury may increase the risk of developing acute and chronic hypopituitarism. Pituitary hormone alterations developed in the early recovery phase after brain injury may have implications for long-term functional recovery. The objective of the present study was to assess the pattern and prevalence of pituitary hormone alterations 3 months after a severe brain injury with relation to functional outcome at a 1-year follow-up. Prospective study at a tertiary university referral centre. A total of 163 patients admitted to neurorehabilitation after severe traumatic brain injury (TBI, n=111) or non-TBI (n=52) were included. The main outcome measures were endocrine alterations 3.3 months (median) after the brain injury and their relationship to the functioning and ability of the patients at a 1-year follow-up, as measured by the Functional Independence Measure and the Glasgow Outcome Scale-Extended. Three months after the injury, elevated stress hormones (i.e. 30 min stimulated cortisol, prolactin and/or IGF1) and/or suppressed gonadal or thyroid hormones were recorded in 68 and 32% of the patients respectively. At 1 year after the injury, lower functioning level (Functional Independence Measure) and lower capability of performing normal life activities (Glasgow Outcome Scale-Extended) were related to both the elevated stress hormones (P≤0.01) and the reduced gonadal and/or thyroid hormones (P≤0.01) measured at 3 months. The present study suggests that brain injury-related endocrine alterations that mimic secondary hypogonadism and hypothyroidism and that occur with elevated stress hormones most probably reflect a prolonged stress response 2-5 months after severe brain injury, rather than pituitary insufficiency per se. These endocrine alterations thus seem to reflect a more severe disease state and relate to 1-year functional outcome. © 2015 European Society of Endocrinology.

The amusic brain: in tune, out of key, and unaware.

PubMed

Peretz, Isabelle; Brattico, Elvira; Järvenpää, Miika; Tervaniemi, Mari

2009-05-01

Like language, music engagement is universal, complex and present early in life. However, approximately 4% of the general population experiences a lifelong deficit in music perception that cannot be explained by hearing loss, brain damage, intellectual deficiencies or lack of exposure. This musical disorder, commonly known as tone-deafness and now termed congenital amusia, affects mostly the melodic pitch dimension. Congenital amusia is hereditary and is associated with abnormal grey and white matter in the auditory cortex and the inferior frontal cortex. In order to relate these anatomical anomalies to the behavioural expression of the disorder, we measured the electrical brain activity of amusic subjects and matched controls while they monitored melodies for the presence of pitch anomalies. Contrary to current reports, we show that the amusic brain can track quarter-tone pitch differences, exhibiting an early right-lateralized negative brain response. This suggests near-normal neural processing of musical pitch incongruities in congenital amusia. It is important because it reveals that the amusic brain is equipped with the essential neural circuitry to perceive fine-grained pitch differences. What distinguishes the amusic from the normal brain is the limited awareness of this ability and the lack of responsiveness to the semitone changes that violate musical keys. These findings suggest that, in the amusic brain, the neural pitch representation cannot make contact with musical pitch knowledge along the auditory-frontal neural pathway.

Comparison of molecular marker expression in early zebrafish brain development following chronic ethanol or morpholino treatment.

PubMed

Zhang, Chengjin; Boa-Amponsem, Oswald; Cole, Gregory J

2017-08-01

This study was undertaken to ascertain whether defined markers of early zebrafish brain development are affected by chronic ethanol exposure or morpholino knockdown of agrin, sonic hedgehog, retinoic acid, and fibroblast growth factors, four signaling molecules that are suggested to be ethanol sensitive. Zebrafish embryos were exposed to 2% ethanol from 6 to 24 hpf or injected with agrin, shha, aldh1a3, or fgf8a morpholinos. In situ hybridization was employed to analyze otx2, pax6a, epha4a, krx20, pax2a, fgf8a, wnt1, and eng2b expression during early brain development. Our results showed that pax6a mRNA expression was decreased in eye, forebrain, and hindbrain of both chronic ethanol exposed and select MO treatments. Epha4a expression in rhombomere R1 boundary was decreased in chronic ethanol exposure and aldh1a3 morphants, lost in fgf8a morphants, but largely unaffected in agrin and shha morphants. Ectopic pax6a and epha4a expression in midbrain was only found in fgf8a morphants. These results suggest that while chronic ethanol induces obvious morphological change in brain architecture, many molecular markers of these brain structures are relatively unaffected by ethanol exposure.

Gyrification brain abnormalities associated with adolescence and early-adulthood cannabis use.

PubMed

Mata, Ignacio; Perez-Iglesias, Rocio; Roiz-Santiañez, Roberto; Tordesillas-Gutierrez, Diana; Pazos, Angel; Gutierrez, Agustin; Vazquez-Barquero, Jose Luis; Crespo-Facorro, Benedicto

2010-03-04

Although cannabis is the most widely used illicit drug in the world, the long-term effect of its use in the brain remains controversial. In order to determine whether adolescence and early-adulthood cannabis use is associated with gross volumetric and gyrification abnormalities in the brain, we set up a cross-sectional study using structural magnetic resonance imaging in a sample of general population subjects. Thirty cannabis-using subjects (mean age, 25.7 years; mean duration of regular use, 8.4 years, range: 3-21) with no history of polydrug use or neurologic/mental disorder and 44 non-using control subjects (mean age, 25.8 years) were included. Cannabis users showed bilaterally decreased concavity of the sulci and thinner sulci in the right frontal lobe. Among non-users, age was significantly correlated with decreased gyrification (i.e., less concave sulci and more convexe gyri) and decreased cortical thickness, supporting the notion of age-related gyrification changes. However, among cannabis users gyrification indices did not show significant dependency on age, age of regular cannabis use initiation, or cumulative exposure to cannabis. These results suggest that cannabis use in adolescence and early-adulthood might involve a premature alteration in cortical gyrification similar to what is normally observed at a later age, probably through disruption of normal neurodevelopment. 2009 Elsevier B.V. All rights reserved.

Inflammatory cytokines in the brain: does the CNS shape immune responses?

PubMed

Owens, T; Renno, T; Taupin, V; Krakowski, M

1994-12-01

Immune responses in the central nervous system (CNS) have traditionally been regarded as representing the intrusion of an unruly, ill-behaved mob of leukocytes into the well-ordered and organized domain of thought and reason. However, results accumulated over the past few years suggest that, far from being an immunologically privileged organ, T lymphocytes may be regular and frequent visitors to the CNS, for purposes of immune surveillance. Here, Trevor Owens and colleagues propose that the brain itself can regulate or shape immune responses therein. Furthermore, given that the immune cells may be subverted to autoimmunity, they suggest that the study of inflammatory autoimmune disease in the brain may shed light on the ability of the local environment to regulate immune responses.

Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

PubMed Central

Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.

2014-01-01

Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229

Statistical distribution of blood serotonin as a predictor of early autistic brain abnormalities.

PubMed

Janusonis, Skirmantas

2005-07-19

A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin) in blood platelets (platelet hyperserotonemia). The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor. The identity of this factor was studied by using a novel, quantitative approach that was applied to published distributions of the platelet 5-HT levels in normal and autistic groups. It was shown that the published data are consistent with the hypothesis that a factor that interferes with brain development in autism may also regulate the release of 5-HT from gut enterochromaffin cells. Numerical analysis revealed that this factor may be non-functional in autistic individuals. At least some biological factors, the abnormal function of which leads to the development of the autistic brain, may regulate the release of 5-HT from the gut years after birth. If the present model is correct, it will allow future efforts to be focused on a limited number of gene candidates, some of which have not been suspected to be involved in autism (such as the 5-HT4 receptor gene) based on currently available clinical and experimental studies.

TALE transcription factors during early development of the vertebrate brain and eye.

PubMed

Schulte, Dorothea; Frank, Dale

2014-01-01

Our brain's cognitive performance arises from the coordinated activities of billions of nerve cells. Despite a high degree of morphological and functional differences, all neurons of the vertebrate central nervous system (CNS) arise from a common field of multipotent progenitors. Cell fate specification and differentiation are directed by multistep processes that include inductive/external cues, such as the extracellular matrix or growth factors, and cell-intrinsic determinants, such as transcription factors and epigenetic modulators of proteins and DNA. Here we review recent findings implicating TALE-homeodomain proteins in these processes. Although originally identified as HOX-cofactors, TALE proteins also contribute to many physiological processes that do not require HOX-activity. Particular focus is, therefore, given to HOX-dependent and -independent functions of TALE proteins during early vertebrate brain development. Additionally, we provide an overview about known upstream and downstream factors of TALE proteins in the developing vertebrate brain and discuss general concepts of how TALE proteins function to modulate neuronal cell fate specification. Copyright © 2013 Wiley Periodicals, Inc.

Early Alterations of Brain Cellular Energy Homeostasis in Huntington Disease Models*

PubMed Central

Mochel, Fanny; Durant, Brandon; Meng, Xingli; O'Callaghan, James; Yu, Hua; Brouillet, Emmanuel; Wheeler, Vanessa C.; Humbert, Sandrine; Schiffmann, Raphael; Durr, Alexandra

2012-01-01

Brain energy deficit has been a suggested cause of Huntington disease (HD), but ATP depletion has not reliably been shown in preclinical models, possibly because of the immediate post-mortem changes in cellular energy metabolism. To examine a potential role of a low energy state in HD, we measured, for the first time in a neurodegenerative model, brain levels of high energy phosphates using microwave fixation, which instantaneously inactivates brain enzymatic activities and preserves in vivo levels of analytes. We studied HD transgenic R6/2 mice at ages 4, 8, and 12 weeks. We found significantly increased creatine and phosphocreatine, present as early as 4 weeks for phosphocreatine, preceding motor system deficits and decreased ATP levels in striatum, hippocampus, and frontal cortex of R6/2 mice. ATP and phosphocreatine concentrations were inversely correlated with the number of CAG repeats. Conversely, in mice injected with 3-nitroproprionic acid, an acute model of brain energy deficit, both ATP and phosphocreatine were significantly reduced. Increased creatine and phosphocreatine in R6/2 mice was associated with decreased guanidinoacetate N-methyltransferase and creatine kinase, both at the protein and RNA levels, and increased phosphorylated AMP-dependent protein kinase (pAMPK) over AMPK ratio. In addition, in 4-month-old knock-in HdhQ111/+ mice, the earliest metabolic alterations consisted of increased phosphocreatine in the frontal cortex and increased the pAMPK/AMPK ratio. Altogether, this study provides the first direct evidence of chronic alteration in homeostasis of high energy phosphates in HD models in the earliest stages of the disease, indicating possible reduced utilization of the brain phosphocreatine pool. PMID:22123819

Early lung retrieval from traumatic brain-dead donors does not compromise outcomes following lung transplantation.

PubMed

Moreno, Paula; Alvarez, Antonio; Illana, Jennifer; Espinosa, Dionisio; Baamonde, Carlos; Cerezo, Francisco; Algar, Francisco Javier; Salvatierra, Angel

2013-06-01

To determine whether lung retrieval from traumatic donors performed within 24 h of brain death has a negative impact on early graft function and survival after lung transplantation (LT), when compared with those retrieved after 24 h. Review of lung transplants performed from traumatic donors over a 17-year period. Recipients were distributed into two groups: transplants from traumatic donor lungs retrieved within 24 h of brain death (Group A), and transplants from traumatic donor lungs retrieved after 24 h of brain death (Group B). Demographic data of donors and recipients, early graft function, perioperative complications and mortality were compared between both groups. Among 356 lung transplants performed at our institution, 132 were from traumatic donors (70% male, 30% female). Group A: 73 (55%); Group B: 59 (45%). There were 53 single, 77 double, and 2 combined LT. Indications were emphysema in 41 (31%), pulmonary fibrosis in 31 (23%), cystic fibrosis in 38 (29%), bronchiectasis in 9 (7%) and other indications in 13 patients (10%). Donor and recipient demographic data, need or cardiopulmonary bypass, postoperative complications and Intensive Care Unit and hospital stay did not differ between groups. Primary graft dysfunction (A vs B): 9 (16%) vs 13 (26%) P = 0.17. PaO2/FiO2 24 h post-transplant (A vs B): 303 mmHg vs 288 mmHg (P = 0.57). Number of acute rejection episodes (A vs B): 0.93 vs 1.49 (P = 0.01). Postoperative intubation time (A vs B): 99 vs 100 h (P = 0.99). 30-day mortality (A vs B): 7 (10%) vs 2 (3.5%) (P = 0.13). Freedom from bronchiolitis obliterans syndrome (A vs B): 82, 72, 37, 22 vs 78, 68, 42, 15%, at 3, 5, 10 and 15 years, respectively (P = 0.889). Survival (A vs B): 65, 54, 46, 42 and 27 vs 60, 50, 45, 43 and 29% at 3, 5, 7, 10 and 15 years, respectively (P = 0.937). In our experience, early lung retrieval after brain death from traumatic donors does not adversely affect early and long-term outcomes after LT.

Sex Differences in Brain Thyroid Hormone Levels during Early Post-Hatching Development in Zebra Finch (Taeniopygia guttata).

PubMed

Yamaguchi, Shinji; Hayase, Shin; Aoki, Naoya; Takehara, Akihiko; Ishigohoka, Jun; Matsushima, Toshiya; Wada, Kazuhiro; Homma, Koichi J

2017-01-01

Thyroid hormones are closely linked to the hatching process in precocial birds. Previously, we showed that thyroid hormones in brain had a strong impact on filial imprinting, an early learning behavior in newly hatched chicks; brain 3,5,3'-triiodothyronine (T3) peaks around hatching and imprinting training induces additional T3 release, thus, extending the sensitive period for imprinting and enabling subsequent other learning. On the other hand, blood thyroid hormone levels have been reported to increase gradually after hatching in altricial species, but it remains unknown how the brain thyroid hormone levels change during post-hatching development of altricial birds. Here, we determined the changes in serum and brain thyroid hormone levels of a passerine songbird species, the zebra finch using radioimmunoassay. In the serum, we found a gradual increase in thyroid hormone levels during post-hatching development, as well as differences between male and female finches. In the brain, there was clear surge in the hormone levels during development in males and females coinciding with the time of fledging, but the onset of the surge of thyroxine (T4) in males preceded that of females, whereas the onset of the surge of T3 in males succeeded that of females. These findings provide a basis for understanding the functions of thyroid hormones during early development and learning in altricial birds.

Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity.

PubMed

Arnoldussen, Ilse A C; Zerbi, Valerio; Wiesmann, Maximilian; Noordman, Rikko H J; Bolijn, Simone; Mutsaers, Martina P C; Dederen, Pieter J W C; Kleemann, Robert; Kooistra, Teake; van Tol, Eric A F; Gross, Gabriele; Schoemaker, Marieke H; Heerschap, Arend; Wielinga, Peter Y; Kiliaan, Amanda J

2016-04-01

Worldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid (ARA) and docosahexaenoic acid (DHA) can reduce the detrimental effects of later obesogenic feeding on lipid metabolism and adipogenesis in an animal model of mild obesity. In the present study, the effects of early dietary ARA and DHA on cognition and brain structure were examined in mildly obesogenic ApoE*3Leiden mouse model. We used cognitive tests and neuroimaging during early and later life. During their early development after weaning (4-13weeks of age), mice were fed a chow diet or ARA and DHA diet for 8 weeks and then switched to a high-fat and high-carbohydrate (HFHC) diet for 12weeks (14-26weeks of age). An HFHC-diet led to increased energy storage in white adipose tissue, increased cholesterol levels, decreased triglycerides levels, increased cerebral blood flow and decreased functional connectivity between brain regions as well as cerebrovascular and gray matter integrity. ARA and DHA intake reduced the HFHC-diet-induced increase in body weight, attenuated plasma triglycerides levels and improved cerebrovasculature, gray matter integrity and functional connectivity in later life. In conclusion, an HFHC diet causes adverse structural brain and metabolic adaptations, most of which can be averted by dietary ARA and DHA intake early in life supporting metabolic flexibility and cerebral integrity later in life. Copyright © 2016 Elsevier Inc. All rights reserved.

Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli

PubMed Central

Field, Brent A.; Buck, Cara L.; McClure, Samuel M.; Nystrom, Leigh E.; Kahneman, Daniel; Cohen, Jonathan D.

2015-01-01

Studies of subjective well-being have conventionally relied upon self-report, which directs subjects’ attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure) by using functional magnetic resonance imaging (fMRI) to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly) the activity of brain mechanisms thought to represent hedonic value. PMID:26158468

Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial

PubMed Central

Clifton, Guy L; Valadka, Alex; Zygun, David; Coffey, Christopher S; Drever, Pamala; Fourwinds, Sierra; Janis, L Scott; Wilde, Elizabeth; Taylor, Pauline; Harshman, Kathy; Conley, Adam; Puccio, Ava; Levin, Harvey S; McCauley, Stephen R; Bucholz, Richard D; Smith, Kenneth R; Schmidt, John H; Scott, James N; Yonas, Howard; Okonkwo, David O

2013-01-01

Summary Background The inconsistent effect of hypothermia treatment on severe brain injury in previous trials might be because hypothermia was induced too late after injury. We aimed to assess whether very early induction of hypothermia improves outcome in patients with severe brain injury. Methods The National Acute Brain Injury Study: Hypothermia II (NABIS: H II) was a randomised, multicentre clinical trial of patients with severe brain injury who were enrolled within 2·5 h of injury at six sites in the USA and Canada. Patients with non-penetrating brain injury who were 16–45 years old and were not responsive to instructions were randomly assigned (1:1) by a random number generator to hypothermia or normothermia. Patients randomly assigned to hypothermia were cooled to 35°C until their trauma assessment was completed. Patients who had none of a second set of exclusion criteria were either cooled to 33°C for 48 h and then gradually rewarmed or treated at normothermia, depending upon their initial treatment assignment. Investigators who assessed the outcome measures were masked to treatment allocation. The primary outcome was the Glasgow outcome scale score at 6 months. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, NCT00178711. Findings Enrolment occurred from December, 2005, to June, 2009, when the trial was terminated for futility. Follow-up was from June, 2006, to December, 2009. 232 patients were initially randomised a mean of 1·6 h (SD 0·5) after injury: 119 to hypothermia and 113 to normothermia. 97 patients (52 in the hypothermia group and 45 in the normothermia group) did not meet any of the second set of exclusion criteria. The mean time to 35°C for the 52 patients in the hypothermia group was 2·6 h (SD 1·2) and to 33°C was 4·4 h (1·5). Outcome was poor (severe disability, vegetative state, or death) in 31 of 52 patients in the hypothermia group and 25 of 56 in the normothermia group (relative

Early metabolic crisis-related brain atrophy and cognition in traumatic brain injury.

PubMed

Wright, Matthew J; McArthur, David L; Alger, Jeffry R; Van Horn, Jack; Irimia, Andrei; Filippou, Maria; Glenn, Thomas C; Hovda, David A; Vespa, Paul

2013-09-01

Traumatic brain injury often results in acute metabolic crisis. We recently demonstrated that this is associated with chronic brain atrophy, which is most prominent in the frontal and temporal lobes. Interestingly, the neuropsychological profile of traumatic brain injury is often characterized as 'frontal-temporal' in nature, suggesting a possible link between acute metabolic crisis-related brain atrophy and neurocognitive impairment in this population. While focal lesions and diffuse axonal injury have a well-established role in the neuropsychological deficits observed following traumatic brain injury, no studies to date have examined the possible contribution of acute metabolic crisis-related atrophy in the neuropsychological sequelae of traumatic brain injury. In the current study we employed positron emission tomography, magnetic resonance imaging, and neuropsychological assessments to ascertain the relationship between acute metabolic crisis-related brain atrophy and neurocognitive outcome in a sample of 14 right-handed traumatic brain injury survivors. We found that acute metabolic crisis-related atrophy in the frontal and temporal lobes was associated with poorer attention, executive functioning, and psychomotor abilities at 12 months post-injury. Furthermore, participants with gross frontal and/or temporal lobe atrophy exhibited numerous clinically significant neuropsychological deficits in contrast to participants with other patterns of brain atrophy. Our findings suggest that interventions that reduce acute metabolic crisis may lead to improved functional outcomes for traumatic brain injury survivors.

A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging.

PubMed

Baroncelli, Laura; Molinaro, Angelo; Cacciante, Francesco; Alessandrì, Maria Grazia; Napoli, Debora; Putignano, Elena; Tola, Jonida; Leuzzi, Vincenzo; Cioni, Giovanni; Pizzorusso, Tommaso

2016-10-01

Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and autistic-like behavioural disturbances, language and speech impairment. Since no data are available about the neural and molecular underpinnings of this disease, we performed a longitudinal analysis of behavioural and pathological alterations associated with CrT deficiency in a CCDS1 mouse model. We found precocious cognitive and autistic-like defects, mimicking the early key features of human CCDS1. Moreover, mutant mice displayed a progressive impairment of short and long-term declarative memory denoting an early brain aging. Pathological examination showed a prominent loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and the accumulation of autofluorescent lipofuscin. Our data suggest that brain Cr depletion causes both early intellectual disability and late progressive cognitive decline, and identify novel targets to design intervention strategies aimed at overcoming brain CCDS1 alterations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?

PubMed Central

Danese, Andrea; J Lewis, Stephanie

2017-01-01

The brain and the immune system are not fully formed at birth, but rather continue to mature in response to the postnatal environment. The two-way interaction between the brain and the immune system makes it possible for childhood psychosocial stressors to affect immune system development, which in turn can affect brain development and its long-term functioning. Drawing from experimental animal models and observational human studies, we propose that the psychoneuroimmunology of early-life stress can offer an innovative framework to understand and treat psychopathology linked to childhood trauma. Early-life stress predicts later inflammation, and there are striking analogies between the neurobiological correlates of early-life stress and of inflammation. Furthermore, there are overlapping trans-diagnostic patterns of association of childhood trauma and inflammation with clinical outcomes. These findings suggest new strategies to remediate the effect of childhood trauma before the onset of clinical symptoms, such as anti-inflammatory interventions and potentiation of adaptive immunity. Similar strategies might be used to ameliorate the unfavorable treatment response described in psychiatric patients with a history of childhood trauma. PMID:27629365

Altered brain response for semantic knowledge in Alzheimer's disease.

PubMed

Wierenga, Christina E; Stricker, Nikki H; McCauley, Ashley; Simmons, Alan; Jak, Amy J; Chang, Yu-Ling; Nation, Daniel A; Bangen, Katherine J; Salmon, David P; Bondi, Mark W

2011-02-01

Word retrieval deficits are common in Alzheimer's disease (AD) and are thought to reflect a degradation of semantic memory. Yet, the nature of semantic deterioration in AD and the underlying neural correlates of these semantic memory changes remain largely unknown. We examined the semantic memory impairment in AD by investigating the neural correlates of category knowledge (e.g., living vs. nonliving) and featural processing (global vs. local visual information). During event-related fMRI, 10 adults diagnosed with mild AD and 22 cognitively normal (CN) older adults named aloud items from three categories for which processing of specific visual features has previously been dissociated from categorical features. Results showed widespread group differences in the categorical representation of semantic knowledge in several language-related brain areas. For example, the right inferior frontal gyrus showed selective brain response for nonliving items in the CN group but living items in the AD group. Additionally, the AD group showed increased brain response for word retrieval irrespective of category in Broca's homologue in the right hemisphere and rostral cingulate cortex bilaterally, which suggests greater recruitment of frontally mediated neural compensatory mechanisms in the face of semantic alteration. Copyright © 2010 Elsevier Ltd. All rights reserved.

Permanent hypopituitarism is rare after structural traumatic brain injury in early childhood.

PubMed

Heather, Natasha L; Jefferies, Craig; Hofman, Paul L; Derraik, José G B; Brennan, Christine; Kelly, Patrick; Hamill, James K M; Jones, Rhys G; Rowe, Deborah L; Cutfield, Wayne S

2012-02-01

We sought to determine the incidence of permanent hypopituitarism in a potentially high-risk group: young children after structural traumatic brain injury (TBI). We conducted a cross-sectional study with longitudinal follow-up. Dynamic tests of pituitary function (GH and ACTH) were performed in all subjects and potential abnormalities critically evaluated. Puberty was clinically staged; baseline thyroid function, prolactin, IGF-I, serum sodium, and osmolality were compared with age-matched data. Diagnosis of GH deficiency was based on an integrated assessment of stimulated GH peak (<5 μg/liter suggestive of deficiency), IGF-I, and growth pattern. ACTH deficiency was diagnosed based on a subnormal response to two serial Synacthen tests (peak cortisol <500 nmol/liter) and a metyrapone test. We studied 198 survivors of structural TBI sustained in early childhood (112 male, age at injury 1.7 ± 1.5 yr) 6.5 ± 3.2 yr after injury. Sixty-four of the injuries (33%) were inflicted and 134 (68%) accidental. Two participants had developed precocious puberty, which is within the expected background population rate. Peak stimulated GH was subnormal in 16 participants (8%), in the context of normal IGF-I and normal growth. Stimulated peak cortisol was low in 17 (8%), but all had normal ACTH function on follow-up. One participant had a transient low serum T(4). Therefore, no cases of hypopituitarism were recorded. Permanent hypopituitarism is rare after both inflicted and accidental structural TBI in early childhood. Precocious puberty was the only pituitary hormone abnormality found, but the prevalence did not exceed that of the normal population.

Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS

PubMed Central

Watanabe, Hama; Shitara, Yoshihiko; Aoki, Yoshinori; Inoue, Takanobu; Tsuchida, Shinya; Takahashi, Naoto; Taga, Gentaro

2017-01-01

A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants. PMID:28196885

Attentional shifts between surfaces: effects on detection and early brain potentials.

PubMed

Pinilla, T; Cobo, A; Torres, K; Valdes-Sosa, M

2001-06-01

Two consecutive events transforming the same illusory surface in transparent motion (brief changes in direction) can be discriminated with ease, but a prolonged interference ( approximately 500 ms) on the discrimination of the second event arises when different surfaces are concerned [Valdes-Sosa, M., Cobo, A., & Pinilla, T. (2000). Attention to object files defined by transparent motion. Journal of Experimental Psychology: Human Perception and Performance, 26(2), 488-505]. Here we further characterise this phenomenon and compare it to the attentional blink AB [Shapiro, K.L., Raymond, J.E., & Arnell, K.M. (1994). Attention to visual pattern information produces the attentional blink in RSVP. Journal of Experimental Psychology: Human Perception and Performance, 20, 357-371]. Similar to the AB, reduced sensitivity (d') was found in the two-surface condition. However, the two-surface cost was associated with a reduced N1 brain response in contrast to reports for AB [Vogel, E.K., Luck, S.J., & Shapiro, K. (1998). Electrophysiological evidence for a postperceptual locus of suppression during the attentional blink. Journal of Experimental Psychology: Human Perception and Performance, 24(6), 1656-1674]. The results from this study indicate that the two-surface cost corresponds to competitive effects in early vision. Reasons for the discrepancy with the AB study are considered.

Pharmacologic inhibition of phospholipase C in the brain attenuates early memory formation in the honeybee (Apis mellifera L.)

PubMed Central

Iino, Shiori; Kubo, Takeo

2018-01-01

ABSTRACT Although the molecular mechanisms involved in learning and memory in insects have been studied intensively, the intracellular signaling mechanisms involved in early memory formation are not fully understood. We previously demonstrated that phospholipase C epsilon (PLCe), whose product is involved in calcium signaling, is almost selectively expressed in the mushroom bodies, a brain structure important for learning and memory in the honeybee. Here, we pharmacologically examined the role of phospholipase C (PLC) in learning and memory in the honeybee. First, we identified four genes for PLC subtypes in the honeybee genome database. Quantitative reverse transcription-polymerase chain reaction revealed that, among these four genes, three, including PLCe, were expressed higher in the brain than in sensory organs in worker honeybees, suggesting their main roles in the brain. Edelfosine and neomycin, pan-PLC inhibitors, significantly decreased PLC activities in homogenates of the brain tissues. These drugs injected into the head of foragers significantly attenuated memory acquisition in comparison with the control groups, whereas memory retention was not affected. These findings suggest that PLC in the brain is involved in early memory formation in the honeybee. To our knowledge, this is the first report of a role for PLC in learning and memory in an insect. PMID:29330349

Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli

PubMed Central

Hasen, Nina S.; Gammie, Stephen C.

2010-01-01

The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2-/- knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female. PMID:21070815

Brain reward system's alterations in response to food and monetary stimuli in overweight and obese individuals.

PubMed

Verdejo-Román, Juan; Vilar-López, Raquel; Navas, Juan F; Soriano-Mas, Carles; Verdejo-García, Antonio

2017-02-01

The brain's reward system is crucial to understand obesity in modern society, as increased neural responsivity to reward can fuel the unhealthy food choices that are driving the growing obesity epidemic. Brain's reward system responsivity to food and monetary rewards in individuals with excessive weight (overweight and obese) versus normal weight controls, along with the relationship between this responsivity and body mass index (BMI) were tested. The sample comprised 21 adults with obesity (BMI > 30), 21 with overweight (BMI between 25 and 30), and 39 with normal weight (BMI < 25). Participants underwent a functional magnetic resonance imaging (fMRI) session while performing two tasks that involve the processing of food (Willing to Pay) and monetary rewards (Monetary Incentive Delay). Neural activations within the brain reward system were compared across the three groups. Curve fit analyses were conducted to establish the association between BMI and brain reward system's response. Individuals with obesity had greater food-evoked responsivity in the dorsal and ventral striatum compared with overweight and normal weight groups. There was an inverted U-shape association between BMI and monetary-evoked responsivity in the ventral striatum, medial frontal cortex, and amygdala; that is, individuals with BMIs between 27 and 32 had greater responsivity to monetary stimuli. Obesity is associated with greater food-evoked responsivity in the ventral and dorsal striatum, and overweight is associated with greater monetary-evoked responsivity in the ventral striatum, the amygdala, and the medial frontal cortex. Findings suggest differential reactivity of the brain's reward system to food versus monetary rewards in obesity and overweight. Hum Brain Mapp 38:666-677, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Overdrinking, swallowing inhibition, and regional brain responses prior to swallowing

PubMed Central

Saker, Pascal; Egan, Gary F.; McKinley, Michael J.; Denton, Derek A.

2016-01-01

In humans, drinking replenishes fluid loss and satiates the sensation of thirst that accompanies dehydration. Typically, the volume of water drunk in response to thirst matches the deficit. Exactly how this accurate metering is achieved is unknown; recent evidence implicates swallowing inhibition as a potential factor. Using fMRI, this study investigated whether swallowing inhibition is present after more water has been drunk than is necessary to restore fluid balance within the body. This proposal was tested using ratings of swallowing effort and measuring regional brain responses as participants prepared to swallow small volumes of liquid while they were thirsty and after they had overdrunk. Effort ratings provided unequivocal support for swallowing inhibition, with a threefold increase in effort after overdrinking, whereas addition of 8% (wt/vol) sucrose to water had minimal effect on effort before or after overdrinking. Regional brain responses when participants prepared to swallow showed increases in the motor cortex, prefrontal cortices, posterior parietal cortex, striatum, and thalamus after overdrinking, relative to thirst. Ratings of swallowing effort were correlated with activity in the right prefrontal cortex and pontine regions in the brainstem; no brain regions showed correlated activity with pleasantness ratings. These findings are all consistent with the presence of swallowing inhibition after excess water has been drunk. We conclude that swallowing inhibition is an important mechanism in the overall regulation of fluid intake in humans. PMID:27791015

Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder.

PubMed

Shen, Mark D; Nordahl, Christine W; Young, Gregory S; Wootton-Gorges, Sandra L; Lee, Aaron; Liston, Sarah E; Harrington, Kayla R; Ozonoff, Sally; Amaral, David G

2013-09-01

Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6-9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6-9, 12-15, and 18-24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 'high-risk' infants having an older sibling with autism spectrum disorder and 22 'low-risk' infants having no relatives with autism spectrum disorder) were imaged at 6-9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12-15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18-24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6-9 months, which persisted and remained elevated at 12-15 and 18-24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12-15 and 18-24 months of age. This is the first magnetic

Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity.

PubMed

Ballard, Peter; Yates, James W T; Yang, Zhenfan; Kim, Dong-Wan; Yang, James Chih-Hsin; Cantarini, Mireille; Pickup, Kathryn; Jordan, Angela; Hickey, Mike; Grist, Matthew; Box, Matthew; Johnström, Peter; Varnäs, Katarina; Malmquist, Jonas; Thress, Kenneth S; Jänne, Pasi A; Cross, Darren

2016-10-15

Approximately one-third of patients with non-small cell lung cancer (NSCLC) harboring tumors with EGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutations (EGFRm) experience disease progression during treatment due to brain metastases. Despite anecdotal reports of EGFR-TKIs providing benefit in some patients with EGFRm NSCLC brain metastases, there is a clinical need for novel EGFR-TKIs with improved efficacy against brain lesions. We performed preclinical assessments of brain penetration and activity of osimertinib (AZD9291), an oral, potent, irreversible EGFR-TKI selective for EGFRm and T790M resistance mutations, and other EGFR-TKIs in various animal models of EGFR-mutant NSCLC brain metastases. We also present case reports of previously treated patients with EGFRm-advanced NSCLC and brain metastases who received osimertinib in the phase I/II AURA study (NCT01802632). Osimertinib demonstrated greater penetration of the mouse blood-brain barrier than gefitinib, rociletinib (CO-1686), or afatinib, and at clinically relevant doses induced sustained tumor regression in an EGFRm PC9 mouse brain metastases model; rociletinib did not achieve tumor regression. Under positron emission tomography micro-dosing conditions, [ 11 C]osimertinib showed markedly greater exposure in the cynomolgus monkey brain than [ 11 C]rociletinib and [ 11 C]gefitinib. Early clinical evidence of osimertinib activity in previously treated patients with EGFRm-advanced NSCLC and brain metastases is also reported. Osimertinib may represent a clinically significant treatment option for patients with EGFRm NSCLC and brain metastases. Further investigation of osimertinib in this patient population is ongoing. Clin Cancer Res; 22(20); 5130-40. ©2016 AACR. ©2016 American Association for Cancer Research.

Signaling Pathway in Early Brain Injury after Subarachnoid Hemorrhage: News Update.

PubMed

Ji, Chengyuan; Chen, Gang

2016-01-01

The annual incidence of subarachnoid hemorrhage (SAH) caused by intracranial aneurysm rupture is approximately 10.5/10 million people in China, making SAH the third most frequently occurring hemorrhage of the intracranial type after cerebral embolism and hypertensive intracerebral hemorrhage. SAH caused by ruptured aneurysm leads to a mortality rate as high as 67 %, and, because of the sudden onset of this disease, approximately 12-15 % of patients die before they can receive effective treatment. Early brain injury (EBI) is the brain damage occurring within the first 72 h after SAH. Two-thirds of mortality caused by SAH occurs within 48 h, mainly as a result of EBI. With the development of molecular biology and medicine microscopy techniques, various signaling pathways involved in EBI after SAH have been revealed. Understanding these signaling pathways may help clinicians treat EBI after SAH and improve long-term prognosis of SAH patients. This chapter summarizes several important signaling pathways implicated in EBI caused by SAH.

Juvenile Traumatic Brain Injury Results in Cognitive Deficits Associated with Impaired Endoplasmic Reticulum Stress and Early Tauopathy.

PubMed

Hylin, Michael J; Holden, Ryan C; Smith, Aidan C; Logsdon, Aric F; Qaiser, Rabia; Lucke-Wold, Brandon P

2018-05-22

The leading cause of death in the juvenile population is trauma, and in particular neurotrauma. The juvenile brain response to neurotrauma is not completely understood. Endoplasmic reticulum (ER) stress has been shown to contribute to injury expansion and behavioral deficits in adult rodents and furthermore has been seen in adult postmortem human brains diagnosed with chronic traumatic encephalopathy. Whether endoplasmic reticulum stress is increased in juveniles with traumatic brain injury (TBI) is poorly delineated. We investigated this important topic using a juvenile rat controlled cortical impact (CCI) model. We proposed that ER stress would be significantly increased in juvenile rats following TBI and that this would correlate with behavioral deficits using a juvenile rat model. A juvenile rat (postnatal day 28) CCI model was used. Binding immunoglobulin protein (BiP) and C/EBP homologous protein (CHOP) were measured at 4 h in the ipsilateral pericontusion cortex. Hypoxia-inducible factor (HIF)-1α was measured at 48 h and tau kinase measured at 1 week and 30 days. At 4 h following injury, BiP and CHOP (markers of ER stress) were significantly elevated in rats exposed to TBI. We also found that HIF-1α was significantly upregulated 48 h following TBI showing delayed hypoxia. The early ER stress activation was additionally asso-ciated with the activation of a known tau kinase, glycogen synthase kinase-3β (GSK-3β), by 1 week. Tau oligomers measured by R23 were significantly increased by 30 days following TBI. The biochemical changes following TBI were associated with increased impulsive-like or anti-anxiety behavior measured with the elevated plus maze, deficits in short-term memory measured with novel object recognition, and deficits in spatial memory measured with the Morris water maze in juvenile rats exposed to TBI. These results show that ER stress was increased early in juvenile rats exposed to TBI, that these rats developed tau oligomers over the

Multisensory stimuli elicit altered oscillatory brain responses at gamma frequencies in patients with schizophrenia

PubMed Central

Stone, David B.; Coffman, Brian A.; Bustillo, Juan R.; Aine, Cheryl J.; Stephen, Julia M.

2014-01-01

Deficits in auditory and visual unisensory responses are well documented in patients with schizophrenia; however, potential abnormalities elicited from multisensory audio-visual stimuli are less understood. Further, schizophrenia patients have shown abnormal patterns in task-related and task-independent oscillatory brain activity, particularly in the gamma frequency band. We examined oscillatory responses to basic unisensory and multisensory stimuli in schizophrenia patients (N = 46) and healthy controls (N = 57) using magnetoencephalography (MEG). Time-frequency decomposition was performed to determine regions of significant changes in gamma band power by group in response to unisensory and multisensory stimuli relative to baseline levels. Results showed significant behavioral differences between groups in response to unisensory and multisensory stimuli. In addition, time-frequency analysis revealed significant decreases and increases in gamma-band power in schizophrenia patients relative to healthy controls, which emerged both early and late over both sensory and frontal regions in response to unisensory and multisensory stimuli. Unisensory gamma-band power predicted multisensory gamma-band power differently by group. Furthermore, gamma-band power in these regions predicted performance in select measures of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) test battery differently by group. These results reveal a unique pattern of task-related gamma-band power in schizophrenia patients relative to controls that may indicate reduced inhibition in combination with impaired oscillatory mechanisms in patients with schizophrenia. PMID:25414652

Repetitive Religious Chanting Modulates the Late-Stage Brain Response to Fear- and Stress-Provoking Pictures

PubMed Central

Gao, Junling; Fan, Jicong; Wu, Bonnie W.; Halkias, Georgios T.; Chau, Maggie; Fung, Peter C.; Chang, Chunqi; Zhang, Zhiguo; Hung, Yeung-Sam; Sik, Hinhung

2017-01-01

echo similar research findings on Christian religious practices and brain responses to negative stimuli. Hence, prayer/religious practices may have cross-cultural universality in emotion regulation. This study shows for the first time that Buddhist chanting, or in a broader sense, repetition of religious prayers will not modulate brain responses to negative stimuli during the early perceptual stage, but only during the late-stage emotional/cognitive processing. PMID:28119651

Blood–Brain Barrier Leakage during Early Epileptogenesis Is Associated with Rapid Remodeling of the Neurovascular Unit

PubMed Central

Breuer, Heike; Leiter, Ina; Märkel, Martin; Bascuñana, Pablo; Michalski, Dominik; Bengel, Frank M.; Löscher, Wolfgang; Meier, Martin; Bankstahl, Jens P.; Härtig, Wolfgang

2018-01-01

Abstract Increased permeability of the blood–brain barrier (BBB) following cerebral injury results in regional extravasation of plasma proteins and can critically contribute to the pathogenesis of epilepsy. Here, we comprehensively explore the spatiotemporal evolution of a main extravasation component, albumin, and illuminate associated responses of the neurovascular unit (NVU) contributing to early epileptogenic neuropathology. We applied translational in vivo MR imaging and complementary immunohistochemical analyses in the widely used rat pilocarpine post–status epilepticus (SE) model. The observed rapid BBB leakage affected major epileptogenesis-associated brain regions, peaked between 1 and 2 d post-SE, and rapidly declined thereafter, accompanied by cerebral edema generally following the same time course. At peak of BBB leakage, serum albumin colocalized with NVU constituents, such as vascular components, neurons, and brain immune cells. Surprisingly, astroglial markers did not colocalize with albumin, and aquaporin-4 (AQP4) was clearly reduced in areas of leaky BBB, indicating a severe disturbance of astrocyte-mediated endothelial-neuronal coupling. In addition, a distinct adaptive reorganization process of the NVU vasculature apparently takes place at sites of albumin presence, substantiated by reduced immunoreactivity of endothelial and changes in vascular basement membrane markers. Taken together, degenerative events at the level of the NVU, affecting vessels, astrocytes, and neurons, seem to outweigh reconstructive processes. Considering the rapidly occurring BBB leakage and subsequent impairment of the NVU, our data support the necessity of a prompt BBB-restoring treatment as one component of rational therapeutic intervention to prevent epileptogenesis and the development of other detrimental sequelae of SE. PMID:29854942

Response of avian embryonic brain to spatially segmented x-ray microbeams.

PubMed

Dilmanian, F A; Morris, G M; Le Duc, G; Huang, X; Ren, B; Bacarian, T; Allen, J C; Kalef-Ezra, J; Orion, I; Rosen, E M; Sandhu, T; Sathé, P; Wu, X Y; Zhong, Z; Shivaprasad, H L

2001-05-01

Duck embryo was studied as a model for assessing the effects of microbeam radiation therapy (MRT) on the human infant brain. Because of the high risk of radiation-induced disruption of the developmental process in the immature brain, conventional wide-beam radiotherapy of brain tumors is seldom carried out in infants under the age of three. Other types of treatment for pediatric brain tumors are frequently ineffective. Recent findings from studies in Grenoble on the brain of suckling rats indicate that MRT could be of benefit for the treatment of early childhood tumors. In our studies, duck embryos were irradiated at 3-4 days prior to hatching. Irradiation was carried out using a single exposure of synchrotron-generated X-rays, either in the form of parallel microplanar beams (microbeams), or as non-segmented broad beam. The individual microplanar beams had a width of 27 microm and height of 11 mm, and a center-to-center spacing of 100 microm. Doses to the exposed areas of embryo brain were 40, 80, 160 and 450 Gy (in-slice dose) for the microbeam, and 6, 12 and 18 Gy for the broad beam. The biological end point employed in the study was ataxia. This neurological symptom of radiation damage to the brain developed within 75 days of hatching. Histopathological analysis of brain tissue did not reveal any radiation induced lesions for microbeam doses of 40-160 Gy (in-slice), although some incidences of ataxia were observed in that dose group. However, severe brain lesions did occur in animals in the 450 Gy microbeam dose groups, and mild lesions in the 18 Gy broad beam dose group. These results indicate that embryonic duck brain has an appreciably higher tolerance to the microbeam modality, as compared to the broad beam modality. When the microbeam dose was normalized to the full volume of the irradiated tissue. i.e., the dose averaged over microbeams and the space between the microbeams, brain tolerance was estimated to be about three times higher to microbeam

Naringin alleviates early brain injury after experimental subarachnoid hemorrhage by reducing oxidative stress and inhibiting apoptosis.

PubMed

Han, Yuwei; Su, Jingyuan; Liu, Xiujuan; Zhao, Yuan; Wang, Chenchen; Li, Xiaoming

2017-07-01

This study aims to clarify the neuroprotective effect of naringin on early brain injury (EBI) following subarachnoid hemorrhage (SAH) and the possible mechanisms of naringin in the treatment of SAH. The endovascular puncture model was performed to induce SAH model in rats and the efficacy of 40mg/kg and 80mg/kg naringin were tested by intraperitoneally administration. SAH grade, neurological score, brain edema, blood-brain barrier permeability, the changes of oxidative stress related factors, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling pathway and neuronal morphology were detected to analyze the potential effect of naringin against SAH. The results demonstrated that naringin significantly ameliorated EBI, including SAH severity, neurologic deficits, brain edema and blood-brain barrier integrity by attenuating SAH-induced oxidative stress and apoptosis, and reduced the oxidant damage and apoptosis by inhibiting the activation of MAPK signaling pathway, which suggested a therapeutic potential of naringin in providing neuroprotection after SAH. Copyright © 2016 Elsevier Inc. All rights reserved.

Law, Responsibility, and the Brain

NASA Astrophysics Data System (ADS)

Mobbs, Dean; Lau, Hakwan C.; Jones, Owen D.; Frith, Chris D.

In perhaps the first attempt to link the brain to mental illness, Hippocrates elegantly wrote that it is the brain that makes us mad or delirious. Epitomizing one of the fundamental assumptions of contemporary neuroscience, Hippocrates' words resonate far beyond the classic philosophical puzzle of mind and body and posit that our behavior, no matter how monstrous, lies at the mercy of our brain's integrity. While clinicopathological observations have long pointed to several putative neurobiological systems as important in antisocial and violent criminal behavior, recent advances in brain-imaging have the potential to provide unparalleled insight. Consequently, brain-imaging studies have reinvigorated the neurophilosophical and legal debate of whether we are free agents in control of our own actions or mere prisoners of a biologically determined brain. In this chapter, we review studies pointing to brain dysfunction in criminally violent individuals and address a range of philosophical and practical issues concerning the use of brainimaging in court. We finally lay out several guidelines for its use in the legal system.

Grammaticality Sensitivity in Children with Early Focal Brain Injury and Children with Specific Language Impairment

ERIC Educational Resources Information Center

Wulfeck, Beverly; Bates, Elizabeth; Krupa-Kwiatkowski, Magda; Saltzman, Danna

2004-01-01

Grammaticality judgments and processing times associated with violation detection were examined in typically developing children, children with focal brain lesions (FL) acquired early in life, and children with specific language impairment (SLI). Grammatical sensitivity in the FL group, while below typically developing children, was above levels…

Interplay between brain stem angiotensins and monocyte chemoattractant protein-1 as a novel mechanism for pressor response after ischemic stroke.

PubMed

Chang, Alice Y W; Li, Faith C H; Huang, Chi-Wei; Wu, Julie C C; Dai, Kuang-Yu; Chen, Chang-Han; Li, Shau-Hsuan; Su, Chia-Hao; Wu, Re-Wen

2014-11-01

Pressor response after stroke commonly leads to early death or susceptibility to stroke recurrence, and detailed mechanisms are still lacking. We assessed the hypothesis that the renin-angiotensin system contributes to pressor response after stroke by differential modulation of the pro-inflammatory chemokine monocyte chemoattractant protein-1 (MCP-1) in the rostral ventrolateral medulla (RVLM), a key brain stem site that maintains blood pressure. We also investigated the beneficial effects of a novel renin inhibitor, aliskiren, against stroke-elicited pressor response. Experiments were performed in male adult Sprague-Dawley rats. Stroke induced by middle cerebral artery occlusion elicited significant pressor response, accompanied by activation of angiotensin II (Ang II)/type I receptor (AT1R) and AT2R signaling, depression of Ang-(1-7)/MasR and Ang IV/AT4R cascade, alongside augmentation of MCP-1/C-C chemokine receptor 2 (CCR2) signaling and neuroinflammation in the RVLM. Stroke-elicited pressor response was significantly blunted by antagonism of AT1R, AT2R or MCP-1/CCR2 signaling, and eliminated by applying Ang-(1-7) or Ang IV into the RVLM. Furthermore, stroke-activated MCP-1/CCR2 signaling was enhanced by AT1R and AT2R activation, and depressed by Ang-(1-7)/MasR and Ang IV/AT4R cascade. Aliskiren inhibited stroke-elicited pressor response via downregulating MCP-1/CCR2 activity and reduced neuroinflammation in the RVLM; these effects were potentiated by Ang-(1-7) or Ang IV. We conclude that whereas Ang II/AT1R or Ang II/AT2R signaling in the brain stem enhances, Ang-(1-7)/MasR or Ang IV/AT4R antagonizes pressor response after stroke by differential modulations of MCP-1 in the RVLM. Furthermore, combined administration of aliskiren and Ang-(1-7) or Ang IV into the brain stem provides more effective amelioration of stroked-induced pressor response. Copyright © 2014 Elsevier Inc. All rights reserved.

Early gray-matter and white-matter concentration in infancy predict later language skills: a whole brain voxel-based morphometry study.

PubMed

Deniz Can, Dilara; Richards, Todd; Kuhl, Patricia K

2013-01-01

Magnetic resonance imaging (MRI) brain scans were obtained from 19 infants at 7 months. Expressive and receptive language performance was assessed at 12 months. Voxel-based morphometry (VBM) identified brain regions where gray-matter and white-matter concentrations at 7 months correlated significantly with children's language scores at 12 months. Early gray-matter concentration in the right cerebellum, early white-matter concentration in the right cerebellum, and early white-matter concentration in the left posterior limb of the internal capsule (PLIC)/cerebral peduncle were positively and strongly associated with infants' receptive language ability at 12 months. Early gray-matter concentration in the right hippocampus was positively and strongly correlated with infants' expressive language ability at 12 months. Our results suggest that the cerebellum, PLIC/cerebral peduncle, and the hippocampus may be associated with early language development. Potential links between these structural predictors and infants' linguistic functions are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Tackling the ‘dyslexia paradox’: reading brain and behavior for early markers of developmental dyslexia

PubMed Central

Ozernov-Palchik, Ola; Gaab, Nadine

2016-01-01

Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5–17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in prereading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure. PMID:26836227

Brain Activations Related to Saccadic Response Conflict are not Sensitive to Time on Task.

PubMed

Beldzik, Ewa; Domagalik, Aleksandra; Oginska, Halszka; Marek, Tadeusz; Fafrowicz, Magdalena

2015-01-01

Establishing a role of the dorsal medial frontal cortex in the performance monitoring and cognitive control has been a challenge to neuroscientists for the past decade. In light of recent findings, the conflict monitoring hypothesis has been elaborated to an action-outcome predictor theory. One of the findings that led to this re-evaluation was the fMRI study in which conflict-related brain activity was investigated in terms of the so-called time on task effect, i.e., a linear increase of the BOLD signal with longer response times. The aim of this study was to investigate brain regions involved in the processing of saccadic response conflict and to account for the time on task effect. A modified spatial cueing task was implemented in the event-related fMRI study with oculomotor responses. The results revealed several brain regions which show higher activity for incongruent trials in comparison to the congruent ones, including pre-supplementary motor area together with the frontal and parietal regions. Further analysis accounting for the effect of response time provided evidence that these brain activations were not sensitive to time on task but reflected purely the congruency effect.

Violence: heightened brain attentional network response is selectively muted in Down syndrome.

PubMed

Anderson, Jeffrey S; Treiman, Scott M; Ferguson, Michael A; Nielsen, Jared A; Edgin, Jamie O; Dai, Li; Gerig, Guido; Korenberg, Julie R

2015-01-01

The ability to recognize and respond appropriately to threat is critical to survival, and the neural substrates subserving attention to threat may be probed using depictions of media violence. Whether neural responses to potential threat differ in Down syndrome is not known. We performed functional MRI scans of 15 adolescent and adult Down syndrome and 14 typically developing individuals, group matched by age and gender, during 50 min of passive cartoon viewing. Brain activation to auditory and visual features, violence, and presence of the protagonist and antagonist were compared across cartoon segments. fMRI signal from the brain's dorsal attention network was compared to thematic and violent events within the cartoons between Down syndrome and control samples. We found that in typical development, the brain's dorsal attention network was most active during violent scenes in the cartoons and that this was significantly and specifically reduced in Down syndrome. When the antagonist was on screen, there was significantly less activation in the left medial temporal lobe of individuals with Down syndrome. As scenes represented greater relative threat, the disparity between attentional brain activation in Down syndrome and control individuals increased. There was a reduction in the temporal autocorrelation of the dorsal attention network, consistent with a shortened attention span in Down syndrome. Individuals with Down syndrome exhibited significantly reduced activation in primary sensory cortices, and such perceptual impairments may constrain their ability to respond to more complex social cues such as violence. These findings may indicate a relative deficit in emotive perception of violence in Down syndrome, possibly mediated by impaired sensory perception and hypoactivation of medial temporal structures in response to threats, with relative preservation of activity in pro-social brain regions. These findings indicate that specific genetic differences associated

Early Cerebral Small Vessel Disease and Brain Volume, Cognition, and Gait

PubMed Central

Smith, Eric E; O'Donnell, Martin; Dagenais, Gilles; Lear, Scott A; Wielgosz, Andreas; Sharma, Mukul; Poirier, Paul; Stotts, Grant; Black, Sandra E; Strother, Stephen; Noseworthy, Michael D; Benavente, Oscar; Modi, Jayesh; Goyal, Mayank; Batool, Saima; Sanchez, Karla; Hill, Vanessa; McCreary, Cheryl R; Frayne, Richard; Islam, Shofiqul; DeJesus, Jane; Rangarajan, Sumathy; Teo, Koon; Yusuf, Salim

2015-01-01

Objective Decline in cognitive function begins by the 40s, and may be related to future dementia risk. We used data from a community-representative study to determine whether there are age-related differences in simple cognitive and gait tests by the 40s, and whether these differences were associated with covert cerebrovascular disease on magnetic resonance imaging (MRI). Methods Between 2010 and 2012, 803 participants aged 40 to 75 years in the Prospective Urban Rural Epidemiological (PURE) study, recruited from prespecified postal code regions centered on 4 Canadian cities, underwent brain MRI and simple tests of cognition and gait as part of a substudy (PURE-MIND). Results Mean age was 58 ± 8 years. Linear decreases in performance on the Montreal Cognitive Assessment, Digit Symbol Substitution Test (DSST), and Timed Up and Go test of gait were seen with each age decade from the 40s to the 70s. Silent brain infarcts were observed in 3% of 40- to 49-year-olds, with increasing prevalence up to 18.9% in 70-year-olds. Silent brain infarcts were associated with slower timed gait and lower volume of supratentorial white matter. Higher volume of supratentorial MRI white matter hyperintensity was associated with slower timed gait and worse performance on DSST, and lower volumes of the supratentorial cortex and white matter, and cerebellum. Interpretation Covert cerebrovascular disease and its consequences on cognitive and gait performance and brain atrophy are manifest in some clinically asymptomatic persons as early as the 5th decade of life. Ann Neurol 2015;77:251–261 PMID:25428654

Dynamic Responses in Brain Networks to Social Feedback: A Dual EEG Acquisition Study in Adolescent Couples

PubMed Central

Kuo, Ching-Chang; Ha, Thao; Ebbert, Ashley M.; Tucker, Don M.; Dishion, Thomas J.

2017-01-01

Adolescence is a sensitive period for the development of romantic relationships. During this period the maturation of frontolimbic networks is particularly important for the capacity to regulate emotional experiences. In previous research, both functional magnetic resonance imaging (fMRI) and dense array electroencephalography (dEEG) measures have suggested that responses in limbic regions are enhanced in adolescents experiencing social rejection. In the present research, we examined social acceptance and rejection from romantic partners as they engaged in a Chatroom Interact Task. Dual 128-channel dEEG systems were used to record neural responses to acceptance and rejection from both adolescent romantic partners and unfamiliar peers (N = 75). We employed a two-step temporal principal component analysis (PCA) and spatial independent component analysis (ICA) approach to statistically identify the neural components related to social feedback. Results revealed that the early (288 ms) discrimination between acceptance and rejection reflected by the P3a component was significant for the romantic partner but not the unfamiliar peer. In contrast, the later (364 ms) P3b component discriminated between acceptance and rejection for both partners and peers. The two-step approach (PCA then ICA) was better able than either PCA or ICA alone in separating these components of the brain's electrical activity that reflected both temporal and spatial phases of the brain's processing of social feedback. PMID:28620292

Brain Oscillations and Diurnal Variations in Hypnotic Responsiveness—A Commentary on “Diurnal Variations in Hypnotic Responsiveness: Is There an Optimal Time to be Hypnotized?”

PubMed Central

Jensen, Mark P.

2016-01-01

A recent study published in the International Journal of Clinical and Experimental Hypnosis reported an interesting diurnal pattern of hypnotic responsivity; specifically, the authors found higher hypnotic responsiveness in a large sample of undergraduates in the morning and early evening. However, they did not have an explanation for this pattern of findings. This pattern is consistent, however, with the theta hypothesis of hypnotic responsivity. Further examination of the associations between brain oscillations and response to hypnosis is needed to determine if specific oscillations such as theta (1) actually facilitate response to some hypnotic suggestions, (2) merely reflect hypnotic responding, or (3) reflect another factor that itself plays a causal role in response to hypnosis. PMID:26599996

Multivariate Brain Prediction of Heart Rate and Skin Conductance Responses to Social Threat.

PubMed

Eisenbarth, Hedwig; Chang, Luke J; Wager, Tor D

2016-11-23

Psychosocial stressors induce autonomic nervous system (ANS) responses in multiple body systems that are linked to health risks. Much work has focused on the common effects of stress, but ANS responses in different body systems are dissociable and may result from distinct patterns of cortical-subcortical interactions. Here, we used machine learning to develop multivariate patterns of fMRI activity predictive of heart rate (HR) and skin conductance level (SCL) responses during social threat in humans (N = 18). Overall, brain patterns predicted both HR and SCL in cross-validated analyses successfully (r HR = 0.54, r SCL = 0.58, both p < 0.0001). These patterns partly reflected central stress mechanisms common to both responses because each pattern predicted the other signal to some degree (r HR→SCL = 0.21 and r SCL→HR = 0.22, both p < 0.01), but they were largely physiological response specific. Both patterns included positive predictive weights in dorsal anterior cingulate and cerebellum and negative weights in ventromedial PFC and local pattern similarity analyses within these regions suggested that they encode common central stress mechanisms. However, the predictive maps and searchlight analysis suggested that the patterns predictive of HR and SCL were substantially different across most of the brain, including significant differences in ventromedial PFC, insula, lateral PFC, pre-SMA, and dmPFC. Overall, the results indicate that specific patterns of cerebral activity track threat-induced autonomic responses in specific body systems. Physiological measures of threat are not interchangeable, but rather reflect specific interactions among brain systems. We show that threat-induced increases in heart rate and skin conductance share some common representations in the brain, located mainly in the vmPFC, temporal and parahippocampal cortices, thalamus, and brainstem. However, despite these similarities, the brain patterns that predict these two autonomic responses

Rebooting the Brain: Using Early Childhood Education to Heal Trauma from Abuse and Neglect

ERIC Educational Resources Information Center

McLintock, Ben

2011-01-01

Abused and neglected children live in a world that usually includes some sort of violence, chaos, and tremendous physical and mental stress. This toxic environment wreaks havoc on a child's developing brain. This article discusses how to use early childhood education to heal trauma from abuse and neglect. It shares the story of two children, Bryce…

Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli.

PubMed

Hasen, Nina S; Gammie, Stephen C

2011-03-01

The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female. Copyright © 2010 Elsevier B.V. All rights reserved.

Minocycline Protects Against NLRP3 Inflammasome-Induced Inflammation and P53-Associated Apoptosis in Early Brain Injury After Subarachnoid Hemorrhage.

PubMed

Li, Jianru; Chen, Jingsen; Mo, Hangbo; Chen, Jingyin; Qian, Cong; Yan, Feng; Gu, Chi; Hu, Qiang; Wang, Lin; Chen, Gao

2016-05-01

Minocycline has beneficial effects in early brain injury (EBI) following subarachnoid hemorrhage (SAH); however, the molecular mechanisms underlying these effects have not been clearly identified. This study was undertaken to determine the influence of minocycline on inflammation and neural apoptosis and the possible mechanisms of these effects in early brain injury following subarachnoid hemorrhage. SAH was induced by the filament perforation model of SAH in male Sprague-Dawley rats. Minocycline or vehicle was given via an intraperitoneal injection 1 h after SAH induction. Minocycline treatment markedly attenuated brain edema secondary to blood-brain barrier (BBB) dysfunction by inhibiting NLRP3 inflammasome activation, which controls the maturation and release of pro-inflammatory cytokines, especially interleukin-1β (IL-1β). Minocycline treatment also markedly reduced the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells. To further identify the potential mechanisms, we demonstrated that minocycline increased Bcl2 expression and reduced the protein expression of P53, Bax, and cleaved caspase-3. In addition, minocycline reduced the cortical levels of reactive oxygen species (ROS), which are closely related to both NLRP3 inflammasome and P53 expression. Minocycline protects against NLRP3 inflammasome-induced inflammation and P53-associated apoptosis in early brain injury following SAH. Minocycline's anti-inflammatory and anti-apoptotic effect may involve the reduction of ROS. Minocycline treatment may exhibit important clinical potentials in the management of SAH.

Early VEGF inhibition attenuates blood-brain barrier disruption in ischemic rat brains by regulating the expression of MMPs.

PubMed

Zhang, Hai-Tao; Zhang, Ping; Gao, Yi; Li, Chen-Long; Wang, Hong-Jun; Chen, Ling-Chao; Feng, Yan; Li, Rui-Yan; Li, Yong-Li; Jiang, Chuan-Lu

2017-01-01

Vascular endothelial growth factor (VEGF) inhibition has been demonstrated to be an effective strategy in preserving the integrity of the blood-brain barrier (BBB) in patients with acute ischemic stroke. Loss of the BBB is the key event associated with morbidity and mortality in these patients. However, the underlying mechanisms remain poorly understood. In the present study, the effects of VEGF inhibition and the possible mechanism that underlies acute cerebral ischemia in rats was investigated. Following the induction of transient middle cerebral artery occlusion for a 90‑min period, either an anti‑VEGF neutralizing antibody (RB‑222; 5 or 10 µg), or IgG (control), was administered by intracerebroventricular injection at 1 h following reperfusion. Functional outcomes, BBB leakage, brain edema, microvessel numbers and the relative protein levels of VEGF, matrix metalloproteinase (MMP)-2, MMP-9, occludin and collagen-IV were then determined using neurological assessments, Evans Blue staining, brain water content, CD31 staining and western blotting. Treatment with RB‑222 at a dose of 5 and 10 µg significantly improved neurological functional outcomes and diminished infarct size, BBB leakage and brain edema compared with the MCAO and IgG groups at 24 h following reperfusion; 10 µg RB‑222 was more effective than a 5 µg dose of the antibody. In addition, RB‑222 reduced the number of immature microvessels, which subsequently attenuated BBB permeability. RB‑222 significantly repressed VEGF expression as well as decreased MMP‑2 and MMP‑9 expression. However, it enhanced occludin and collagen‑IV levels in the ischemic rat brain compared with the MCAO and IgG groups. Taken together, the results indicate that early inhibition of VEGF may have significant potential against cerebral ischemia, partly by regulating the expression of MMPs.

Brain Development

MedlinePlus

... All Early Learning Child Care Early Literacy Early Math and Science Language and Communication Play School Readiness ... Brain Development from Birth Series Let's Talk About Math: Early Math Video Series Resource | Disponible en español ...

Statistical distribution of blood serotonin as a predictor of early autistic brain abnormalities

PubMed Central

Janušonis, Skirmantas

2005-01-01

Background A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin) in blood platelets (platelet hyperserotonemia). The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor. Results The identity of this factor was studied by using a novel, quantitative approach that was applied to published distributions of the platelet 5-HT levels in normal and autistic groups. It was shown that the published data are consistent with the hypothesis that a factor that interferes with brain development in autism may also regulate the release of 5-HT from gut enterochromaffin cells. Numerical analysis revealed that this factor may be non-functional in autistic individuals. Conclusion At least some biological factors, the abnormal function of which leads to the development of the autistic brain, may regulate the release of 5-HT from the gut years after birth. If the present model is correct, it will allow future efforts to be focused on a limited number of gene candidates, some of which have not been suspected to be involved in autism (such as the 5-HT4 receptor gene) based on currently available clinical and experimental studies. PMID

Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients.

PubMed

Alsaadi, Hanin M; Van Vugt, Dean A

2015-11-01

This study examined the effect of insulin sensitivity on the responsiveness of appetite regulatory brain regions to visual food cues. Nineteen participants diagnosed with polycystic ovary syndrome (PCOS) were divided into insulin-sensitive (n=8) and insulin-resistant (n=11) groups based on the homeostatic model assessment of insulin resistance (HOMA2-IR). Subjects underwent functional magnetic resonance imaging (fMRI) while viewing food pictures following water or dextrose consumption. The corticolimbic blood oxygen level dependent (BOLD) responses to high-calorie (HC) or low-calorie (LC) food pictures were compared within and between groups. BOLD responses to food pictures were reduced during a glucose challenge in numerous corticolimbic brain regions in insulin-sensitive but not insulin-resistant subjects. Furthermore, the degree of insulin resistance positively correlated with the corticolimbic BOLD response in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate and ventral tegmental area (VTA) in response to HC pictures, and in the dorsolateral prefrontal cortex (DLPFC), mPFC, anterior cingulate, and insula in response to LC pictures following a glucose challenge. BOLD signal in the OFC, midbrain, hippocampus, and amygdala following a glucose challenge correlated with HOMA2-IR in response to HC-LC pictures. We conclude that the normal inhibition of corticolimbic brain responses to food pictures during a glucose challenge is compromised in insulin-resistant subjects. The increase in brain responsiveness to food pictures during postprandial hyperinsulinemia may lead to greater non-homeostatic eating and perpetuate obesity in insulin-resistant subjects.

Brain responses mediating idiom comprehension: gender and hemispheric differences.

PubMed

Kana, Rajesh K; Murdaugh, Donna L; Wolfe, Kelly R; Kumar, Sandhya L

2012-07-27

Processing figurative language, such as idioms, is unique in that it requires one to make associations between words and non-literal meanings that are contextually appropriate. At the neural level, processing idiomatic phrases has been linked to recruitment of bilateral dorsolateral prefrontal cortices (DLPFC), the left temporal cortex, superior medial prefrontal gyrus (MPFC), and the left inferior frontal gyrus (LIFG). This functional MRI study examined the brain responses associated with processing idiomatic compared to literal sentences. In addition, gender differences in neural responses associated with language comprehension were also explored. In an fMRI scanner, thirty-six healthy adult volunteers viewed sentences that were either literal or idiomatic in nature, and answered subsequent comprehension questions. This sentence comprehension tasks activated mainly prefrontal language areas (LIFG, LSFG, and RMFG). Consistent with previous findings, idiomatic sentences showed increased response in LIFG. These results are discussed in the backdrop of the graded salience hypothesis. Furthermore, we found gender differences in brain activation and functional connectivity during this task. Women showed greater overall activation than men when comprehending literal and idiomatic sentences; whereas men had significantly greater functional connectivity between LIFG and LMTG than women across tasks. Overall, the findings of this study highlight the gender differences in neural responses associated with figurative language comprehension. Published by Elsevier B.V.

Blood gene expression profiling of an early acetaminophen response.

PubMed

Bushel, P R; Fannin, R D; Gerrish, K; Watkins, P B; Paules, R S

2017-06-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.

Blood Gene Expression Profiling of an Early Acetaminophen Response

PubMed Central

Bushel, Pierre R.; Fannin, Rick D.; Gerrish, Kevin; Watkins, Paul B.; Paules, Richard S.

2018-01-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24 hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. PMID:26927286

Opiate-induced Changes in Brain Adenosine Levels and Narcotic Drug Responses

PubMed Central

Wu, Manhong; Sahbaie, Peyman; Zheng, Ming; Lobato, Robert; Boison, Detlev; Clark, J. David; Peltz, Gary

2012-01-01

We have very little information about the metabolomic changes that mediate neurobehavioral responses, including addiction. It was possible that opioid-induced metabolomic changes in brain could mediate some of the pharmacodynamic effects of opioids. To investigate this, opiate-induced brain metabolomic responses were profiled using a semi-targeted method in C57BL/6 and 129Sv1 mice, which exhibit extreme differences in their tendency to become opiate dependent. Escalating morphine doses (10–40 mg/kg) administered over a 4-day period selectively induced a two-fold decrease (p<0.00005) in adenosine abundance in the brainstem of C57BL/6 mice, which exhibited symptoms of narcotic drug dependence; but did not decrease adenosine abundance in 129Sv1 mice, which do not exhibit symptoms of dependence. Based on this finding, the effect of adenosine on dependence was investigated in genetically engineered mice with alterations in adenosine tone in the brain and in pharmacologic experiments. Morphine withdrawal behaviors were significantly diminished (P<0.0004) in genetically engineered mice with reduced adenosine tone in the brainstem, and by treatment with an adenosine receptor1 (A1) agonist (2-chloro-N6-cyclopentyladenosine, 0.5 mg/kg) or an A2a receptor (A2a) antagonist (SCH 58261 1 mg/kg). These results indicate that adenosine homeostasis plays a crucial role in narcotic drug responses. Opiate-induced changes in brain adenosine levels may explain many important neurobehavioral features associated with opiate addiction and withdrawal. PMID:23098802

Left hemisphere regions are critical for language in the face of early left focal brain injury.

PubMed

Raja Beharelle, Anjali; Dick, Anthony Steven; Josse, Goulven; Solodkin, Ana; Huttenlocher, Peter R; Levine, Susan C; Small, Steven L

2010-06-01

A predominant theory regarding early stroke and its effect on language development, is that early left hemisphere lesions trigger compensatory processes that allow the right hemisphere to assume dominant language functions, and this is thought to underlie the near normal language development observed after early stroke. To test this theory, we used functional magnetic resonance imaging to examine brain activity during category fluency in participants who had sustained pre- or perinatal left hemisphere stroke (n = 25) and in neurologically normal siblings (n = 27). In typically developing children, performance of a category fluency task elicits strong involvement of left frontal and lateral temporal regions and a lesser involvement of right hemisphere structures. In our cohort of atypically developing participants with early stroke, expressive and receptive language skills correlated with activity in the same left inferior frontal regions that support language processing in neurologically normal children. This was true independent of either the amount of brain injury or the extent that the injury was located in classical cortical language processing areas. Participants with bilateral activation in left and right superior temporal-inferior parietal regions had better language function than those with either predominantly left- or right-sided unilateral activation. The advantage conferred by left inferior frontal and bilateral temporal involvement demonstrated in our study supports a strong predisposition for typical neural language organization, despite an intervening injury, and argues against models suggesting that the right hemisphere fully accommodates language function following early injury.

Task by stimulus interactions in brain responses during Chinese character processing.

PubMed

Yang, Jianfeng; Wang, Xiaojuan; Shu, Hua; Zevin, Jason D

2012-04-02

In the visual word recognition literature, it is well understood that various stimulus effects interact with behavioral task. For example, effects of word frequency are exaggerated and effects of spelling-to-sound regularity are reduced in the lexical decision task, relative to reading aloud. Neuroimaging studies of reading often examine effects of task and stimulus properties on brain activity independently, but potential interactions between task demands and stimulus effects have not been extensively explored. To address this issue, we conducted lexical decision and symbol detection tasks using stimuli that varied parametrically in their word-likeness, and tested for task by stimulus class interactions. Interactions were found throughout the reading system, such that stimulus selectivity was observed during the lexical decision task, but not during the symbol detection task. Further, the pattern of stimulus selectivity was directly related to task difficulty, so that the strongest brain activity was observed to the most word-like stimuli that required "no" responses, whereas brain activity to words, which elicit rapid and accurate "yes" responses were relatively weak. This is in line with models that argue for task-dependent specialization of brain regions, and contrasts with the notion of task-independent stimulus selectivity in the reading system. Copyright © 2012 Elsevier Inc. All rights reserved.

Oxytocin selectively modulates brain response to stimuli probing social synchrony.

PubMed

Levy, Jonathan; Goldstein, Abraham; Zagoory-Sharon, Orna; Weisman, Omri; Schneiderman, Inna; Eidelman-Rothman, Moranne; Feldman, Ruth

2016-01-01

The capacity to act collectively within groups has led to the survival and thriving of Homo sapiens. A central group collaboration mechanism is "social synchrony," the coordination of behavior during joint action among affiliative members, which intensifies under threat. Here, we tested brain response to vignettes depicting social synchrony among combat veterans trained for coordinated action and following life-threatening group experience, versus controls, as modulated by oxytocin (OT), a neuropeptide supporting social synchrony. Using a randomized, double-blind, within-subject design, 40 combat-trained and control male veterans underwent magnetoencephalography (MEG) twice following OT/placebo administration while viewing two social vignettes rated as highly synchronous: pleasant male social gathering and coordinated unit during combat. Both vignettes activated a wide response across the social brain in the alpha band; the combat scene triggered stronger activations. Importantly, OT effects were modulated by prior experience. Among combat veterans, OT attenuated the increased response to combat stimuli in the posterior superior temporal sulcus (pSTS) - a hub of social perception, action observation, and mentalizing - and enhanced activation in the inferior parietal lobule (IPL) to the pleasant social scene. Among controls, OT enhanced inferior frontal gyrus (IFG) response to combat cues, demonstrating selective OT effects on mirror-neuron and mentalizing networks. OT-enhanced mirror network activity was dampened in veterans reporting higher posttraumatic symptoms. Results demonstrate that the social brain responds online, via modulation of alpha rhythms, to stimuli probing social synchrony, particularly those involving threat to survival, and OT's enhancing versus anxiolytic effects are sensitive to salient experiences within social groups. Copyright © 2015 Elsevier Inc. All rights reserved.

Responsive Infant Caregiving: Eight Proven Practices

ERIC Educational Resources Information Center

Leifield, Lisa; Sanders, Tisha Bennett

2007-01-01

Brain research has confirmed what many early care and education professionals have known all along--warm, nurturing relationships among babies, toddlers, and their caregivers support children's development. The nurturing adult-child interaction that supports children's development is called "responsive care". Responsive care is supported by small…

Early response to psychological trauma--what GPs can do.

PubMed

Wade, Darryl; Howard, Alexandra; Fletcher, Susan; Cooper, John; Forbes, David

2013-09-01

There is a high prevalence of psychological trauma exposure among primary care patients. General practitioners are well placed to provide appropriate support for patients coping with trauma. This article outlines an evidence-based early response to psychological trauma. Psychological first aid is the preferred approach in providing early assistance to patients who have experienced a traumatic event. General practitioners can be guided by five empirically derived principles in their early response: promoting a sense of safety, calming, self efficacy, connectedness and hope. Structured psychological interventions, including psychological debriefing, are not routinely recommended in the first few weeks following trauma exposure. General practitioner self care is an important aspect of providing post-trauma patient care.

Bilinguals Use Language-Control Brain Areas More Than Monolinguals to Perform Non-Linguistic Switching Tasks

PubMed Central

Rodríguez-Pujadas, Aina; Sanjuán, Ana; Ventura-Campos, Noelia; Román, Patricia; Martin, Clara; Barceló, Francisco; Costa, Albert; Ávila, César

2013-01-01

We tested the hypothesis that early bilinguals use language-control brain areas more than monolinguals when performing non-linguistic executive control tasks. We do so by exploring the brain activity of early bilinguals and monolinguals in a task-switching paradigm using an embedded critical trial design. Crucially, the task was designed such that the behavioural performance of the two groups was comparable, allowing then to have a safer comparison between the corresponding brain activity in the two groups. Despite the lack of behavioural differences between both groups, early bilinguals used language-control areas – such as left caudate, and left inferior and middle frontal gyri – more than monolinguals, when performing the switching task. Results offer direct support for the notion that, early bilingualism exerts an effect in the neural circuitry responsible for executive control. This effect partially involves the recruitment of brain areas involved in language control when performing domain-general executive control tasks, highlighting the cross-talk between these two domains. PMID:24058456

The Richness of Task-Evoked Hemodynamic Responses Defines a Pseudohierarchy of Functionally Meaningful Brain Networks

PubMed Central

Orban, Pierre; Doyon, Julien; Petrides, Michael; Mennes, Maarten; Hoge, Richard; Bellec, Pierre

2015-01-01

Functional magnetic resonance imaging can measure distributed and subtle variations in brain responses associated with task performance. However, it is unclear whether the rich variety of responses observed across the brain is functionally meaningful and consistent across individuals. Here, we used a multivariate clustering approach that grouped brain regions into clusters based on the similarity of their task-evoked temporal responses at the individual level, and then established the spatial consistency of these individual clusters at the group level. We observed a stable pseudohierarchy of task-evoked networks in the context of a delayed sequential motor task, where the fractionation of networks was driven by a gradient of involvement in motor sequence preparation versus execution. In line with theories about higher-level cognitive functioning, this gradient evolved in a rostro-caudal manner in the frontal lobe. In addition, parcellations in the cerebellum and basal ganglia matched with known anatomical territories and fiber pathways with the cerebral cortex. These findings demonstrate that subtle variations in brain responses associated with task performance are systematic enough across subjects to define a pseudohierarchy of task-evoked networks. Such networks capture meaningful functional features of brain organization as shaped by a given cognitive context. PMID:24729172

Untangling the Effect of Head Acceleration on Brain Responses to Blast Waves

PubMed Central

Mao, Haojie; Unnikrishnan, Ginu; Rakesh, Vineet; Reifman, Jaques

2015-01-01

Multiple injury-causing mechanisms, such as wave propagation, skull flexure, cavitation, and head acceleration, have been proposed to explain blast-induced traumatic brain injury (bTBI). An accurate, quantitative description of the individual contribution of each of these mechanisms may be necessary to develop preventive strategies against bTBI. However, to date, despite numerous experimental and computational studies of bTBI, this question remains elusive. In this study, using a two-dimensional (2D) rat head model, we quantified the contribution of head acceleration to the biomechanical response of brain tissues when exposed to blast waves in a shock tube. We compared brain pressure at the coup, middle, and contre-coup regions between a 2D rat head model capable of simulating all mechanisms (i.e., the all-effects model) and an acceleration-only model. From our simulations, we determined that head acceleration contributed 36–45% of the maximum brain pressure at the coup region, had a negligible effect on the pressure at the middle region, and was responsible for the low pressure at the contre-coup region. Our findings also demonstrate that the current practice of measuring rat brain pressures close to the center of the brain would record only two-thirds of the maximum pressure observed at the coup region. Therefore, to accurately capture the effects of acceleration in experiments, we recommend placing a pressure sensor near the coup region, especially when investigating the acceleration mechanism using different experimental setups. PMID:26458125

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

PubMed Central

2013-01-01

Background A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Methods/Design Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. Discussion We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use.

PubMed

Bernier, Denise; Cookey, Jacob; McAllindon, David; Bartha, Robert; Hanstock, Christopher C; Newman, Aaron J; Stewart, Sherry H; Tibbo, Philip G

2013-10-17

A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding

Scalp-recorded slow EEG responses generated in response to hemodynamic changes in the human brain.

PubMed

Vanhatalo, S; Tallgren, P; Becker, C; Holmes, M D; Miller, J W; Kaila, K; Voipio, J

2003-09-01

To study whether hemodynamic changes in human brain generate scalp-EEG responses. Direct current EEG (DC-EEG) was recorded from 12 subjects during 5 non-invasive manipulations that affect intracranial hemodynamics by different mechanisms: bilateral jugular vein compression (JVC), head-up tilt (HUT), head-down tilt (HDT), Valsalva maneuver (VM), and Mueller maneuver (MM). DC shifts were compared to changes in cerebral blood volume (CBV) measured by near-infrared spectroscopy (NIRS). DC shifts were observed during all manipulations with highest amplitudes (up to 250 microV) at the midline electrodes, and the most pronounced changes (up to 15 microV/cm) in the DC voltage gradient around vertex. In spite of inter-individual variation in both amplitude and polarity, the DC shifts were consistent and reproducible for each subject and they showed a clear temporal correlation with changes in CBV. Our results indicate that hemodynamic changes in human brain are associated with marked DC shifts that cannot be accounted for by intracortical neuronal or glial currents. Instead, the data are consistent with a non-neuronal generator mechanism that is associated with the blood-brain barrier. These findings have direct implications for mechanistic interpretation of slow EEG responses in various experimental paradigms.

Detectability of early brain meningitis with magnetic resonance imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Runge, V.M.; Wells, J.W.; Williams, N.M.

1995-08-01

The ability of high-field (1.5 T) magnetic resonance imaging (MRI) to detect early brain meningitis was evaluated in a canine model. Contrast dose, timing postinjection, and imaging technique (specifically the use of magnetization transfer) were assessed. Imaging of five canines was performed at 1.5 T 24 hours after injection of Cowans staphylococcus into the cisterna magna. Two control animals also were imaged using the same protocol. Contrast doses of 0.1, 0.3, and 0.8 mmol/kg gadoteridol were compared. Scans were performed at 2, 13, and 22 minutes after an initial injection of 0.1 mmol/kg. Thirty minutes after the initial injection ofmore » contrast, a supplemental dose of 0.2 mmol/kg was given. Scans were then repeated at 2, 12, and 22 minutes after this dose was administered. A second supplemental contrast injection of 0.5 mmol/kg was given at 70 minutes, and immediate postinjection scans with and without MT were acquired. Results. In the animals receiving a cisternal injection of bacteria, the degree of meningeal enhancement was greatest at 0.8 mmol/kg, intermediate at 0.3 mmol/kg, and least at 0.1 mmol/kg. Scans in control studies did not demonstrate abnormal meningeal enhancement. High-contrast dose, MT, and acquisition of immediate postcontrast scans all resulted in statistically significant improvement. On masked film review, abnormal meningeal enhancement was noted in only 2 of 5 experimental dogs at a dose of 0.1 mmol/kg (regardless of the use of MT) compared with all animals at a dose of 0.3 mmol/kg. In 18 of 37 dogs (paired scans with and without MT), when abnormal enhancement was noted, the use of MT improved the visualization of abnormal meningeal enhancement. In early brain meningitis, high-contrast dose (0.3 mmol/kg), MT, and scanning immediately after injection improve detection of abnormal meningeal enhancement, thus facilitating the diagnosis of meningitis. Of these factors, contrast dose is the most important. 14 refs., 9 figs., 2 tabs.« less

Right or wrong? The brain's fast response to morally objectionable statements.

PubMed

Van Berkum, Jos J A; Holleman, Bregje; Nieuwland, Mante; Otten, Marte; Murre, Jaap

2009-09-01

How does the brain respond to statements that clash with a person's value system? We recorded event-related brain potentials while respondents from contrasting political-ethical backgrounds completed an attitude survey on drugs, medical ethics, social conduct, and other issues. Our results show that value-based disagreement is unlocked by language extremely rapidly, within 200 to 250 ms after the first word that indicates a clash with the reader's value system (e.g., "I think euthanasia is an acceptable/unacceptable..."). Furthermore, strong disagreement rapidly influences the ongoing analysis of meaning, which indicates that even very early processes in language comprehension are sensitive to a person's value system. Our results testify to rapid reciprocal links between neural systems for language and for valuation.

Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

PubMed

Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

2014-07-01

Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

PubMed Central

Leclercq, Sophie; Mian, Firoz M.; Stanisz, Andrew M.; Bindels, Laure B.; Cambier, Emmanuel; Ben-Amram, Hila; Koren, Omry; Forsythe, Paul; Bienenstock, John

2017-01-01

There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria. PMID:28375200

Neurocognitive Brain Response to Transient Impairment of Wernicke's Area

PubMed Central

Mason, Robert A.; Prat, Chantel S.; Just, Marcel Adam

2014-01-01

This study examined how the brain system adapts and reconfigures its information processing capabilities to maintain cognitive performance after a key cortical center [left posterior superior temporal gyrus (LSTGp)] is temporarily impaired during the performance of a language comprehension task. By applying repetitive transcranial magnetic stimulation (rTMS) to LSTGp and concurrently assessing the brain response with functional magnetic resonance imaging, we found that adaptation consisted of 1) increased synchronization between compensating regions coupled with a decrease in synchronization within the primary language network and 2) a decrease in activation at the rTMS site as well as in distal regions, followed by their recovery. The compensatory synchronization included 3 centers: The contralateral homolog (RSTGp) of the area receiving rTMS, areas adjacent to the rTMS site, and a region involved in discourse monitoring (medial frontal gyrus). This approach reveals some principles of network-level adaptation to trauma with potential application to traumatic brain injury, stroke, and seizure. PMID:23322403

Neurocognitive brain response to transient impairment of Wernicke's area.

PubMed

Mason, Robert A; Prat, Chantel S; Just, Marcel Adam

2014-06-01

This study examined how the brain system adapts and reconfigures its information processing capabilities to maintain cognitive performance after a key cortical center [left posterior superior temporal gyrus (LSTGp)] is temporarily impaired during the performance of a language comprehension task. By applying repetitive transcranial magnetic stimulation (rTMS) to LSTGp and concurrently assessing the brain response with functional magnetic resonance imaging, we found that adaptation consisted of 1) increased synchronization between compensating regions coupled with a decrease in synchronization within the primary language network and 2) a decrease in activation at the rTMS site as well as in distal regions, followed by their recovery. The compensatory synchronization included 3 centers: The contralateral homolog (RSTGp) of the area receiving rTMS, areas adjacent to the rTMS site, and a region involved in discourse monitoring (medial frontal gyrus). This approach reveals some principles of network-level adaptation to trauma with potential application to traumatic brain injury, stroke, and seizure.

Optical mapping of the brain activity in children with Down's syndrome

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Lu, Fengmei

2018-02-01

Down's syndrome (DS) has been shown to be associated with many neurological complications, including cognitive deficits, seizures, early-onset dementia that resembles Alzheimer's disease, and neurological complications of systemic disorders. DS patients show to have poor performance in executive functions (EF) and fine motor skills. In this study, we examined the brain hemodynamic responses and brain activation patterns of DS children during the completion of EF tasks. Revealing its neural mechanism of DS is not only able to contribute to the early intervention of this children with DS, but also increase understanding of developmental cascades in childhood.

Neurovascular coupling and energy metabolism in the developing brain

PubMed Central

Kozberg, M.; Hillman, E.

2016-01-01

In the adult brain, increases in local neural activity are almost always accompanied by increases in local blood flow. However, many functional imaging studies of the newborn and developing human brain have observed patterns of hemodynamic responses that differ from adult responses. Among the proposed mechanisms for the observed variations is that neurovascular coupling itself is still developing in the perinatal brain. Many of the components thought to be involved in actuating and propagating this hemodynamic response are known to still be developing postnatally, including perivascular cells such as astrocytes and pericytes. Both neural and vascular networks expand and are then selectively pruned over the first year of human life. Additionally, the metabolic demands of the newborn brain are still evolving. These changes are highly likely to affect early postnatal neurovascular coupling, and thus may affect functional imaging signals in this age group. This chapter will discuss the literature relating to neurovascular development. Potential effects of normal and aberrant development of neurovascular coupling on the newborn brain will also be explored, as well as ways to effectively utilize imaging techniques that rely on hemodynamic modulation such as fMRI and NIRS in younger populations. PMID:27130418

Rat strain differences in brain structure and neurochemistry in response to binge alcohol.

PubMed

Zahr, Natalie M; Mayer, Dirk; Rohlfing, Torsten; Hsu, Oliver; Vinco, Shara; Orduna, Juan; Luong, Richard; Bell, Richard L; Sullivan, Edith V; Pfefferbaum, Adolf

2014-01-01

Ventricular enlargement is a robust phenotype of the chronically dependent alcoholic human brain, yet the mechanism of ventriculomegaly is unestablished. Heterogeneous stock Wistar rats administered binge EtOH (3 g/kg intragastrically every 8 h for 4 days to average blood alcohol levels (BALs) of 250 mg/dL) demonstrate profound but reversible ventricular enlargement and changes in brain metabolites (e.g., N-acetylaspartate (NAA) and choline-containing compounds (Cho)). Here, alcohol-preferring (P) and alcohol-nonpreferring (NP) rats systematically bred from heterogeneous stock Wistar rats for differential alcohol drinking behavior were compared with Wistar rats to determine whether genetic divergence and consequent morphological and neurochemical variation affect the brain's response to binge EtOH treatment. The three rat lines were dosed equivalently and approached similar BALs. Magnetic resonance imaging and spectroscopy evaluated the effects of binge EtOH on brain. As observed in Wistar rats, P and NP rats showed decreases in NAA. Neither P nor NP rats, however, responded to EtOH intoxication with ventricular expansion or increases in Cho levels as previously noted in Wistar rats. Increases in ventricular volume correlated with increases in Cho in Wistar rats. The latter finding suggests that ventricular volume expansion is related to adaptive changes in brain cell membranes in response to binge EtOH. That P and NP rats responded differently to EtOH argues for intrinsic differences in their brain cell membrane composition. Further, differential metabolite responses to EtOH administration by rat strain implicate selective genetic variation as underlying heterogeneous effects of chronic alcoholism in the human condition.

Behavioural and brain responses related to Internet search and memory.

PubMed

Dong, Guangheng; Potenza, Marc N

2015-10-01

The ready availability of data via searches on the Internet has changed how many people seek and perhaps store and recall information, although the brain mechanisms underlying these processes are not well understood. This study investigated brain mechanisms underlying Internet-based vs. non-Internet-based searching. The results showed that Internet searching was associated with lower accuracy in recalling information as compared with traditional book searching. During functional magnetic resonance imaging, Internet searching was associated with less regional brain activation in the left ventral stream, the association area of the temporal-parietal-occipital cortices, and the middle frontal cortex. When comparing novel items with remembered trials, Internet-based searching was associated with higher brain activation in the right orbitofrontal cortex and lower brain activation in the right middle temporal gyrus when facing those novel trials. Brain activations in the middle temporal gyrus were inversely correlated with response times, and brain activations in the orbitofrontal cortex were positively correlated with self-reported search impulses. Taken together, the results suggest that, although Internet-based searching may have facilitated the information-acquisition process, this process may have been performed more hastily and be more prone to difficulties in recollection. In addition, people appear less confident in recalling information learned through Internet searching and that recent Internet searching may promote motivation to use the Internet. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Sex-Steroid Hormone Manipulation Reduces Brain Response to Reward.

PubMed

Macoveanu, Julian; Henningsson, Susanne; Pinborg, Anja; Jensen, Peter; Knudsen, Gitte M; Frokjaer, Vibe G; Siebner, Hartwig R

2016-03-01

Mood disorders are twice as frequent in women than in men. Risk mechanisms for major depression include adverse responses to acute changes in sex-steroid hormone levels, eg, postpartum in women. Such adverse responses may involve an altered processing of rewards. Here, we examine how women's vulnerability for mood disorders is linked to sex-steroid dynamics by investigating the effects of a pharmacologically induced fluctuation in ovarian sex steroids on the brain response to monetary rewards. In a double-blinded placebo controlled study, healthy women were randomized to receive either placebo or the gonadotropin-releasing hormone agonist (GnRHa) goserelin, which causes a net decrease in sex-steroid levels. Fifty-eight women performed a gambling task while undergoing functional MRI at baseline, during the mid-follicular phase, and again following the intervention. The gambling task enabled us to map regional brain activity related to the magnitude of risk during choice and to monetary reward. The GnRHa intervention caused a net reduction in ovarian sex steroids (estradiol and testosterone) and increased depression symptoms. Compared with placebo, GnRHa reduced amygdala's reactivity to high monetary rewards. There was a positive association between the individual changes in testosterone and changes in bilateral insula response to monetary rewards. Our data provide evidence for the involvement of sex-steroid hormones in reward processing. A blunted amygdala response to rewarding stimuli following a rapid decline in sex-steroid hormones may reflect a reduced engagement in positive experiences. Abnormal reward processing may constitute a neurobiological mechanism by which sex-steroid fluctuations provoke mood disorders in susceptible women.

Eye movement related brain responses to emotional scenes during free viewing

PubMed Central

Simola, Jaana; Torniainen, Jari; Moisala, Mona; Kivikangas, Markus; Krause, Christina M.

2013-01-01

Emotional stimuli are preferentially processed over neutral stimuli. Previous studies, however, disagree on whether emotional stimuli capture attention preattentively or whether the processing advantage is dependent on allocation of attention. The present study investigated attention and emotion processes by measuring brain responses related to eye movement events while 11 participants viewed images selected from the International Affective Picture System (IAPS). Brain responses to emotional stimuli were compared between serial and parallel presentation. An “emotional” set included one image with high positive or negative valence among neutral images. A “neutral” set comprised four neutral images. The participants were asked to indicate which picture—if any—was emotional and to rate that picture on valence and arousal. In the serial condition, the event-related potentials (ERPs) were time-locked to the stimulus onset. In the parallel condition, the ERPs were time-locked to the first eye entry on an image. The eye movement results showed facilitated processing of emotional, especially unpleasant information. The EEG results in both presentation conditions showed that the LPP (“late positive potential”) amplitudes at 400–500 ms were enlarged for the unpleasant and pleasant pictures as compared to neutral pictures. Moreover, the unpleasant scenes elicited stronger responses than pleasant scenes. The ERP results did not support parafoveal emotional processing, although the eye movement results suggested faster attention capture by emotional stimuli. Our findings, thus, suggested that emotional processing depends on overt attentional resources engaged in the processing of emotional content. The results also indicate that brain responses to emotional images can be analyzed time-locked to eye movement events, although the response amplitudes were larger during serial presentation. PMID:23970856

The Roots of Individuality: Brain Waves and Perception.

ERIC Educational Resources Information Center

Rosenfeld, Anne H.; Rosenfeld, Sam A.

Described is research using computer techniques to study the brain's perceptual systems in both normal and pathological groups, including hyperactive children (6-12 years old). Reviewed are the early studies of A. Petrie, M. Buchsbaum, and J. Silverman using the electroencephalograph to obtain AER (average evoked response) records of…

Activation of the endoplasmic reticulum stress response by the amyloid-beta 1-40 peptide in brain endothelial cells.

PubMed

Fonseca, Ana Catarina R G; Ferreiro, Elisabete; Oliveira, Catarina R; Cardoso, Sandra M; Pereira, Cláudia F

2013-12-01

Neurovascular dysfunction arising from endothelial cell damage is an early pathogenic event that contributes to the neurodegenerative process occurring in Alzheimer's disease (AD). Since the mechanisms underlying endothelial dysfunction are not fully elucidated, this study was aimed to explore the hypothesis that brain endothelial cell death is induced upon the sustained activation of the endoplasmic reticulum (ER) stress response by amyloid-beta (Aβ) peptide, which deposits in the cerebral vessels in many AD patients and transgenic mice. Incubation of rat brain endothelial cells (RBE4 cell line) with Aβ1-40 increased the levels of several markers of ER stress-induced unfolded protein response (UPR), in a time-dependent manner, and affected the Ca(2+) homeostasis due to the release of Ca(2+) from this intracellular store. Finally, Aβ1-40 was shown to activate both mitochondria-dependent and -independent apoptotic cell death pathways. Enhanced release of cytochrome c from mitochondria and activation of the downstream caspase-9 were observed in cells treated with Aβ1-40 concomitantly with caspase-12 activation. Furthermore, Aβ1-40 activated the apoptosis effectors' caspase-3 and promoted the translocation of apoptosis-inducing factor (AIF) to the nucleus demonstrating the involvement of caspase-dependent and -independent mechanisms during Aβ-induced endothelial cell death. In conclusion, our data demonstrate that ER stress plays a significant role in Aβ1-40-induced apoptotic cell death in brain endothelial cells suggesting that ER stress-targeted therapeutic strategies might be useful in AD to counteract vascular defects and ultimately neurodegeneration. © 2013.

Brain Structure Changes Visualized in Early- and Late-Onset Blind Subjects

PubMed Central

Leporé, Natasha; Voss, Patrice; Lepore, Franco; Chou, Yi-Yu; Fortin, Madeleine; Gougoux, Frédéric; Lee, Agatha D.; Brun, Caroline; Lassonde, Maryse; Madsen, Sarah K.; Toga, Arthur W.; Thompson, Paul M.

2009-01-01

We examine 3D patterns of volume differences in the brain associated with blindness, in subjects grouped according to early and late onset. Using tensor-based morphometry, we map volume reductions and gains in 16 early-onset (EB) and 16 late-onset (LB) blind adults (onset <5 and >14 years old, respectively) relative to 16 matched sighted controls. Each subject’s structural MRI was fluidly registered to a common template. Anatomical differences between groups were mapped based on statistical analysis of the resulting deformation fields revealing profound deficits in primary and secondary visual cortices for both blind groups. Regions outside the occipital lobe showed significant hypertrophy, suggesting widespread compensatory adaptations. EBs but not LBs showed deficits in the splenium and hypertrophy in the isthmus. Gains in the isthmus and non-occipital white matter were more widespread in the EBs. These differences may reflect regional alterations in late neurodevelopmental processes, such as myelination, that continue into adulthood. PMID:19643183

Modeling and simulation of blast-induced, early-time intracranial wave physics leading to traumatic brain injury.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ford, Corey C.; Taylor, Paul Allen

The objective of this modeling and simulation study was to establish the role of stress wave interactions in the genesis of traumatic brain injury (TBI) from exposure to explosive blast. A high resolution (1 mm{sup 3} voxels), 5 material model of the human head was created by segmentation of color cryosections from the Visible Human Female dataset. Tissue material properties were assigned from literature values. The model was inserted into the shock physics wave code, CTH, and subjected to a simulated blast wave of 1.3 MPa (13 bars) peak pressure from anterior, posterior and lateral directions. Three dimensional plots ofmore » maximum pressure, volumetric tension, and deviatoric (shear) stress demonstrated significant differences related to the incident blast geometry. In particular, the calculations revealed focal brain regions of elevated pressure and deviatoric (shear) stress within the first 2 milliseconds of blast exposure. Calculated maximum levels of 15 KPa deviatoric, 3.3 MPa pressure, and 0.8 MPa volumetric tension were observed before the onset of significant head accelerations. Over a 2 msec time course, the head model moved only 1 mm in response to the blast loading. Doubling the blast strength changed the resulting intracranial stress magnitudes but not their distribution. We conclude that stress localization, due to early time wave interactions, may contribute to the development of multifocal axonal injury underlying TBI. We propose that a contribution to traumatic brain injury from blast exposure, and most likely blunt impact, can occur on a time scale shorter than previous model predictions and before the onset of linear or rotational accelerations traditionally associated with the development of TBI.« less

Health responsibility and workplace health promotion among women: early detection of cancer.

PubMed

Kushnir, T; Rabinowitz, S; Melamed, S; Weisberg, E; Ribak, J

1995-01-01

The importance of health responsibility as one aspect of a health-promoting lifestyle has been emphasized repeatedly. Yet there are only a few empirical studies of its role in preventive behavior. We examined the relationship between health responsibility and early-detection practices for breast and cervical cancer. A group of 253 women employees of a large industrial company participated in a cancer screening program subsidized by the employer. They completed questionnaires assessing health responsibility and reported early-detection practices: frequency of breast self-examination and physician breast examinations, frequency of Pap tests, and time lapsed since last Pap test and breast examinations. Health responsibility was a significant independent predictor of breast examination indicators but not of Pap tests. Education level was an important predictor for Pap tests, and age predicted most early-detection practices. The findings lend some support to the role of health responsibility in initiating breast examinations. Better prediction of early-detection practices could be achieved by adding cognitive and emotional components to the existing responsibility scale and by distinguishing between retrospective and prospective responsibility.

Wavelet analysis of head acceleration response under dirac excitation for early oedema detection.

PubMed

Kostopoulos, V; Loutas, T H; Derdas, C; Douzinas, E

2008-04-01

The present work deals with the application of an innovative in-house developed wavelet-based methodology for the analysis of the acceleration responses of a human head complex model as a simulated diffused oedema progresses. The human head complex has been modeled as a structure consisting of three confocal prolate spheroids, whereas the three defined regions by the system of spheroids, from the outside to the inside, represent the scull, the region of cerebrospinal fluid, and the brain tissue. A Dirac-like pulse has been used to excite the human head complex model and the acceleration response of the system has been calculated and analyzed via the wavelet-based methodology. For the purpose of the present analysis, a wave propagation commercial finite element code, LS-DYNA 3D, has been used. The progressive diffused oedema was modeled via consecutive increases in brain volume accompanied by a decrease in brain density. It was shown that even a small increase in brain volume (at the level of 0.5%) can be identified by the effect it has on the vibration characteristics of the human head complex. More precisely, it was found that for some of the wavelet decomposition levels, the energy content changes monotonically as the brain volume increases, thus providing a useful index of monitoring an oncoming brain oedema before any brain damage appears due to uncontrolled intracranial hypertension. For the purpose of the present work and for the levels of brain volume increase considered in the present analysis, no pressure increase was assumed into the cranial vault and, associatively, no brain compliance variation.

Presence of early stage cancer does not impair the early protein metabolic response to major surgery

PubMed Central

Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

2017-01-01

Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the

Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

PubMed

Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

2017-06-01

Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after

Steroid hormones, stress and the adolescent brain: a comparative perspective.

PubMed

Brown, G R; Spencer, K A

2013-09-26

Steroid hormones, including those produced by the gonads and the adrenal glands, are known to influence brain development during sensitive periods of life. Until recently, most brain organisation was assumed to take place during early stages of development, with relatively little neurogenesis or brain re-organisation during later stages. However, an increasing body of research has shown that the developing brain is also sensitive to steroid hormone exposure during adolescence (broadly defined as the period from nutritional independence to sexual maturity). In this review, we examine how steroid hormones that are produced by the gonads and adrenal glands vary across the lifespan in a range of mammalian and bird species, and we summarise the evidence that steroid hormone exposure influences behavioural and brain development during early stages of life and during adolescence in these two taxonomic groups. Taking a cross-species, comparative perspective reveals that the effects of early exposure to steroid hormones depend upon the stage of development at birth or hatching, as measured along the altricial-precocial dimension. We then review the evidence that exposure to stress during adolescence impacts upon the developing neuroendocrine systems, the brain and behaviour. Current research suggests that the effects of adolescent stress vary depending upon the sex of the individual and type of stressor, and the effects of stress could involve several neural systems, including the serotonergic and dopaminergic systems. Experience of stressors during adolescence could also influence brain development via the close interactions between the stress hormone and gonadal hormone axes. While sensitivity of the brain to steroid hormones during early life and adolescence potentially leaves the developing organism vulnerable to external adversities, developmental plasticity also provides an opportunity for the developing organism to respond to current circumstances and for behavioural

Autonomic and brain responses associated with empathy deficits in autism spectrum disorder

PubMed Central

Eilam‐Stock, Tehila; Zhou, Thomas; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Hof, Patrick R.; Friston, Karl J.

2015-01-01

Abstract Accumulating evidence suggests that autonomic signals and their cortical representations are closely linked to emotional processes, and that related abnormalities could lead to social deficits. Although socio‐emotional impairments are a defining feature of autism spectrum disorder (ASD), empirical evidence directly supporting the link between autonomic, cortical, and socio‐emotional abnormalities in ASD is still lacking. In this study, we examined autonomic arousal indexed by skin conductance responses (SCR), concurrent cortical responses measured by functional magnetic resonance imaging, and effective brain connectivity estimated by dynamic causal modeling in seventeen unmedicated high‐functioning adults with ASD and seventeen matched controls while they performed an empathy‐for‐pain task. Compared to controls, adults with ASD showed enhanced SCR related to empathetic pain, along with increased neural activity in the anterior insular cortex, although their behavioral empathetic pain discriminability was reduced and overall SCR was decreased. ASD individuals also showed enhanced correlation between SCR and neural activities in the anterior insular cortex. Importantly, significant group differences in effective brain connectivity were limited to greater reduction in the negative intrinsic connectivity of the anterior insular cortex in the ASD group, indicating a failure in attenuating anterior insular responses to empathetic pain. These results suggest that aberrant interoceptive precision, as indexed by abnormalities in autonomic activity and its central representations, may underlie empathy deficits in ASD. Hum Brain Mapp 36:3323–3338, 2015. © 2015 The Authors Human Brain Mapping Published byWiley Periodicals, Inc. PMID:25995134

Brain Magnetic Resonance Imaging as First-Line Investigation for Growth Hormone Deficiency Diagnosis in Early Childhood.

PubMed

Pampanini, Valentina; Pedicelli, Stefania; Gubinelli, Jessica; Scirè, Giuseppe; Cappa, Marco; Boscherini, Brunetto; Cianfarani, Stefano

2015-01-01

The diagnosis of growth hormone (GH) deficiency (GHD) in infancy and early childhood is not straightforward. GH stimulation tests are unsafe and unreliable in infants, and normative data are lacking. This study aims to investigate whether brain magnetic resonance imaging (MRI) may replace GH stimulation tests in the diagnosis of GHD in children younger than 4 years. We examined a retrospective cohort, with longitudinal follow-up, of 68 children consecutively diagnosed with GHD before the age of 4 years. The prevalence of hypothalamic-pituitary (HP) alterations at MRI and the associations with age and either isolated GHD (IGHD) or multiple pituitary hormone deficiency (MPHD) were assessed. The prevalences of IGHD and MPHD were 54.4 and 45.6%, respectively. In the first group, brain MRI showed abnormalities in 83.8%: isolated pituitary hypoplasia in 48.7% and complex defects in 35.1%. In patients with MPHD, MRI showed complex alterations in 100%. All children younger than 24 months showed HP MRI abnormalities, regardless of the diagnosis. Complex defects were found in 94% of patients younger than 12 months and in 75% of patients between 13 and 24 months. Our data suggest that brain MRI may represent the first-line investigation for diagnosing GHD in infancy and early childhood. © 2015 S. Karger AG, Basel.

The effects of age, sex, and hormones on emotional conflict-related brain response during adolescence

PubMed Central

Cservenka, Anita; Stroup, Madison L.; Etkin, Amit; Nagel, Bonnie J.

2015-01-01

While cognitive and emotional systems both undergo development during adolescence, few studies have explored top-down inhibitory control brain activity in the context of affective processing, critical to informing adolescent psychopathology. In this study, we used functional magnetic resonance imaging to examine brain response during an Emotional Conflict (EmC) Task across 10–15-year-old youth. During the EmC Task, participants indicated the emotion of facial expressions, while disregarding emotion-congruent and incongruent words printed across the faces. We examined the relationships of age, sex, and gonadal hormones with brain activity on Incongruent vs. Congruent trials. Age was negatively associated with middle frontal gyrus activity, controlling for performance and movement confounds. Sex differences were present in occipital and parietal cortices, and were driven by activation in females, and deactivation in males to Congruent trials. Testosterone was negatively related with frontal and striatal brain response in males, and cerebellar and precuneus response in females. Estradiol was negatively related with fronto-cerebellar, cingulate, and precuneus brain activity in males, and positively related with occipital response in females. To our knowledge, this is the first study reporting the effects of age, sex, and sex steroids during an emotion-cognition task in adolescents. Further research is needed to examine longitudinal development of emotion-cognition interactions and deviations in psychiatric disorders in adolescence. PMID:26175008

The effects of age, sex, and hormones on emotional conflict-related brain response during adolescence.

PubMed

Cservenka, Anita; Stroup, Madison L; Etkin, Amit; Nagel, Bonnie J

2015-10-01

While cognitive and emotional systems both undergo development during adolescence, few studies have explored top-down inhibitory control brain activity in the context of affective processing, critical to informing adolescent psychopathology. In this study, we used functional magnetic resonance imaging to examine brain response during an Emotional Conflict (EmC) Task across 10-15-year-old youth. During the EmC Task, participants indicated the emotion of facial expressions, while disregarding emotion-congruent and incongruent words printed across the faces. We examined the relationships of age, sex, and gonadal hormones with brain activity on Incongruent vs. Congruent trials. Age was negatively associated with middle frontal gyrus activity, controlling for performance and movement confounds. Sex differences were present in occipital and parietal cortices, and were driven by activation in females, and deactivation in males to Congruent trials. Testosterone was negatively related with frontal and striatal brain response in males, and cerebellar and precuneus response in females. Estradiol was negatively related with fronto-cerebellar, cingulate, and precuneus brain activity in males, and positively related with occipital response in females. To our knowledge, this is the first study reporting the effects of age, sex, and sex steroids during an emotion-cognition task in adolescents. Further research is needed to examine longitudinal development of emotion-cognition interactions and deviations in psychiatric disorders in adolescence. Copyright © 2015 Elsevier Inc. All rights reserved.

Adaptive neuroplastic responses in early and late hemispherectomized monkeys.

PubMed

Burke, Mark W; Kupers, Ron; Ptito, Maurice

2012-01-01

Behavioural recovery in children who undergo medically required hemispherectomy showcase the remarkable ability of the cerebral cortex to adapt and reorganize following insult early in life. Case study data suggest that lesions sustained early in childhood lead to better recovery compared to those that occur later in life. In these children, it is possible that neural reorganization had begun prior to surgery but was masked by the dysfunctional hemisphere. The degree of neural reorganization has been difficult to study systematically in human infants. Here we present a 20-year culmination of data on our nonhuman primate model (Chlorocebus sabeus) of early-life hemispherectomy in which behavioral recovery is interpreted in light of plastic processes that lead to the anatomical reorganization of the early-damaged brain. The model presented here suggests that significant functional recovery occurs after the removal of one hemisphere in monkeys with no preexisting neurological dysfunctions. Human and primate studies suggest a critical role for subcortical and brainstem structures as well as corticospinal tracts in the neuroanatomical reorganization which result in the remarkable behavioral recovery following hemispherectomy. The non-human primate model presented here offers a unique opportunity for studying the behavioral and functional neuroanatomical reorganization that underlies developmental plasticity.

Novel insights into early neuroanatomical evolution in penguins from the oldest described penguin brain endocast.

PubMed

Proffitt, J V; Clarke, J A; Scofield, R P

2016-08-01

Digital methodologies for rendering the gross morphology of the brain from X-ray computed tomography data have expanded our current understanding of the origin and evolution of avian neuroanatomy and provided new perspectives on the cognition and behavior of birds in deep time. However, fossil skulls germane to extracting digital endocasts from early stem members of extant avian lineages remain exceptionally rare. Data from early-diverging species of major avian subclades provide key information on ancestral morphologies in Aves and shifts in gross neuroanatomical structure that have occurred within those groups. Here we describe data on the gross morphology of the brain from a mid-to-late Paleocene penguin fossil from New Zealand. This most basal and geochronologically earliest-described endocast from the penguin clade indicates that described neuroanatomical features of early stem penguins, such as lower telencephalic lateral expansion, a relatively wider cerebellum, and lack of cerebellar folding, were present far earlier in penguin history than previously inferred. Limited dorsal expansion of the wulst in the new fossil is a feature seen in outgroup waterbird taxa such as Gaviidae (Loons) and diving Procellariiformes (Shearwaters, Diving Petrels, and allies), indicating that loss of flight may not drastically affect neuroanatomy in diving taxa. Wulst enlargement in the penguin lineage is first seen in the late Eocene, at least 25 million years after loss of flight and cooption of the flight stroke for aquatic diving. Similar to the origin of avian flight, major shifts in gross brain morphology follow, but do not appear to evolve quickly after, acquisition of a novel locomotor mode. Enlargement of the wulst shows a complex pattern across waterbirds, and may be linked to sensory modifications related to prey choice and foraging strategy. © 2016 Anatomical Society.

Early changes in brain structure correlate with language outcomes in children with neonatal encephalopathy.

PubMed

Shapiro, Kevin A; Kim, Hosung; Mandelli, Maria Luisa; Rogers, Elizabeth E; Gano, Dawn; Ferriero, Donna M; Barkovich, A James; Gorno-Tempini, Maria Luisa; Glass, Hannah C; Xu, Duan

2017-01-01

Global patterns of brain injury correlate with motor, cognitive, and language outcomes in survivors of neonatal encephalopathy (NE). However, it is still unclear whether local changes in brain structure predict specific deficits. We therefore examined whether differences in brain structure at 6 months of age are associated with neurodevelopmental outcomes in this population. We enrolled 32 children with NE, performed structural brain MR imaging at 6 months, and assessed neurodevelopmental outcomes at 30 months. All subjects underwent T1-weighted imaging at 3 T using a 3D IR-SPGR sequence. Images were normalized in intensity and nonlinearly registered to a template constructed specifically for this population, creating a deformation field map. We then used deformation based morphometry (DBM) to correlate variation in the local volume of gray and white matter with composite scores on the Bayley Scales of Infant and Toddler Development (Bayley-III) at 30 months. Our general linear model included gestational age, sex, birth weight, and treatment with hypothermia as covariates. Regional brain volume was significantly associated with language scores, particularly in perisylvian cortical regions including the left supramarginal gyrus, posterior superior and middle temporal gyri, and right insula, as well as inferior frontoparietal subcortical white matter. We did not find significant correlations between regional brain volume and motor or cognitive scale scores. We conclude that, in children with a history of NE, local changes in the volume of perisylvian gray and white matter at 6 months are correlated with language outcome at 30 months. Quantitative measures of brain volume on early MRI may help identify infants at risk for poor language outcomes.

Mdivi-1 ameliorates early brain injury after subarachnoid hemorrhage via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis.

PubMed

Fan, Lin-Feng; He, Ping-You; Peng, Yu-Cong; Du, Qing-Hua; Ma, Yi-Jun; Jin, Jian-Xiang; Xu, Hang-Zhe; Li, Jian-Ru; Wang, Zhi-Jiang; Cao, Sheng-Long; Li, Tao; Yan, Feng; Gu, Chi; Wang, Lin; Chen, Gao

2017-11-01

Aberrant modulation of mitochondrial dynamic network, which shifts the balance of fusion and fission towards fission, is involved in brain damage of various neurodegenerative diseases including Parkinson's disease, Huntington's disease and Alzheimer's disease. A recent research has shown that the inhibition of mitochondrial fission alleviates early brain injury after experimental subarachnoid hemorrhage, however, the underlying molecular mechanisms have remained to be elucidated. This study was undertaken to characterize the effects of the inhibition of dynamin-related protein-1 (Drp1, a dominator of mitochondrial fission) on blood-brain barrier (BBB) disruption and neuronal apoptosis following SAH and the potential mechanisms. The endovascular perforation model of SAH was performed in adult male Sprague Dawley rats. The results indicated Mdivi-1(a selective Drp1 inhibitor) reversed the morphologic changes of mitochondria and Drp1 translocation, reduced ROS levels, ameliorated the BBB disruption and brain edema remarkably, decreased the expression of MMP-9 and prevented degradation of tight junction proteins-occludin, claudin-5 and ZO-1. Mdivi-1 administration also inhibited the nuclear translocation of nuclear factor-kappa B (NF-κB), leading to decreased expressions of TNF-ɑ, IL-6 and IL-1ß. Moreover, Mdivi-1 treatment attenuated neuronal cell death and improved neurological outcome. To investigate the underlying mechanisms further, we determined that Mdivi-1 reduced p-PERK, p-eIF2α, CHOP, cleaved caspase-3 and Bax expression as well as increased Bcl-2 expression. Rotenone (a selective inhibitor of mitochondrial complexes I) abolished both the anti-BBB disruption and anti-apoptosis effects of Mdivi-1. In conclusion, these data implied that excessive mitochondrial fission might inhibit mitochondrial complex I to become a cause of oxidative stress in SAH, and the inhibition of Drp1 by Mdivi-1 attenuated early brain injury after SAH probably via the suppression

Approaching the biology of human parental attachment: brain imaging, oxytocin and coordinated assessments of mothers and fathers.

PubMed

Swain, J E; Kim, P; Spicer, J; Ho, S S; Dayton, C J; Elmadih, A; Abel, K M

2014-09-11

Brain networks that govern parental response to infant signals have been studied with imaging techniques over the last 15 years. The complex interaction of thoughts and behaviors required for sensitive parenting enables the formation of each individual's first social bonds and critically shapes development. This review concentrates on magnetic resonance imaging experiments which directly examine the brain systems involved in parental responses to infant cues. First, we introduce themes in the literature on parental brain circuits studied to date. Next, we present a thorough chronological review of state-of-the-art fMRI studies that probe the parental brain with a range of baby audio and visual stimuli. We also highlight the putative role of oxytocin and effects of psychopathology, as well as the most recent work on the paternal brain. Taken together, a new model emerges in which we propose that cortico-limbic networks interact to support parental brain responses to infants. These include circuitry for arousal/salience/motivation/reward, reflexive/instrumental caring, emotion response/regulation and integrative/complex cognitive processing. Maternal sensitivity and the quality of caregiving behavior are likely determined by the responsiveness of these circuits during early parent-infant experiences. The function of these circuits is modifiable by current and early-life experiences, hormonal and other factors. Severe deviation from the range of normal function in these systems is particularly associated with (maternal) mental illnesses - commonly, depression and anxiety, but also schizophrenia and bipolar disorder. Finally, we discuss the limits and extent to which brain imaging may broaden our understanding of the parental brain given our current model. Developments in the understanding of the parental brain may have profound implications for long-term outcomes in families across risk, resilience and possible interventions. This article is part of a Special Issue

Early developmental gene enhancers affect subcortical volumes in the adult human brain.

PubMed

Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

2016-05-01

Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Neuropsychiatric subsyndromes and brain metabolic network dysfunctions in early onset Alzheimer's disease.

PubMed

Ballarini, Tommaso; Iaccarino, Leonardo; Magnani, Giuseppe; Ayakta, Nagehan; Miller, Bruce L; Jagust, William J; Gorno-Tempini, Maria Luisa; Rabinovici, Gil D; Perani, Daniela

2016-12-01

Neuropsychiatric symptoms (NPSs) often occur in early-age-of-onset Alzheimer's disease (EOAD) and cluster into sub-syndromes (SSy). The aim of this study was to investigate the association between 18 F-FDG-PET regional and connectivity-based brain metabolic dysfunctions and neuropsychiatric SSy. NPSs were assessed in 27 EOAD using the Neuropsychiatric Inventory and further clustered into four SSy (apathetic, hyperactivity, affective, and psychotic SSy). Eighty-five percent of EOAD showed at least one NPS. Voxel-wise correlations between SSy scores and brain glucose metabolism (assessed with 18 F-FDG positron emission tomography) were studied. Interregional correlation analysis was used to explore metabolic connectivity in the salience (aSN) and default mode networks (DMN) in a larger sample of EOAD (N = 51) and Healthy Controls (N = 57). The apathetic, hyperactivity, and affective SSy were highly prevalent (>60%) as compared to the psychotic SSy (33%). The hyperactivity SSy scores were associated with increase of glucose metabolism in frontal and limbic structures, implicated in behavioral control. A comparable positive correlation with part of the same network was found for the affective SSy scores. On the other hand, the apathetic SSy scores were negatively correlated with metabolism in the bilateral orbitofrontal and dorsolateral frontal cortex known to be involved in motivation and decision-making processes. Consistent with these SSy regional correlations with brain metabolic dysfunction, the connectivity analysis showed increases in the aSN and decreases in the DMN. Behavioral abnormalities in EOAD are associated with specific dysfunctional changes in brain metabolic activity, in particular in the aSN that seems to play a crucial role in NPSs in EOAD. Hum Brain Mapp 37:4234-4247, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Preterm birth and maternal responsiveness during childhood are associated with brain morphology in adolescence.

PubMed

Frye, Richard E; Malmberg, Benjamin; Swank, Paul; Smith, Karen; Landry, Susan

2010-09-01

Although supportive parenting has been shown to have positive effects on development, the neurobiological basis of supportive parenting has not been investigated. Thirty-three adolescents were systemically selected from a longitudinal study on child development based on maternal responsiveness during childhood, a measure of supportive parenting, and whether they were born term or preterm. We analyzed the effect of preterm birth on hemispheric and regional (frontal, temporal, parietal) cortical thickness and surface area using mixed-model analysis while also considering the effect of brain hemisphere (left vs. right). We then determined whether these factors were moderated by maternal responsiveness during childhood. Preterm birth was associated with regional and hemispheric differences in cortical thickness and surface area. Maternal responsiveness during childhood moderated hemispheric cortical thickness. Adolescence with mothers that were inconsistently responsive during childhood demonstrated greater overall cortical thickness and greater asymmetry in cortical thickness during adolescence as compared to adolescence with mothers who were consistently responsive or unresponsive during childhood. Maternal responsiveness and preterm birth did not interact. These data suggest that changes in brain morphology associated with preterm birth continue into adolescence and support the notion that the style of maternal-child interactions during childhood influence brain development into adolescence.

[Long-term effects of early hyperbaric oxygen therapy on neonatal rats with hypoxic-ischemic brain damage].

PubMed

Liu, Mei-Na; Zhuang, Si-Qi; Zhang, Hong-Yu; Qin, Zhao-Yuan; Li, Xiao-Yu

2006-06-01

The application and therapeutic effect of hyperbaric oxygen (HBO) in hypoxic-ischemic brain damage (HIBD) remains controversial. Previous studies have focused on the early pathological and biochemical outcomes and there is a lack of long-term functional evaluation. This study was designed to evaluate the long-term pathological and behavioral changes of early HBO therapy on neonatal rats with HIBD. Postnatal 7 days (PD7) rat pups were randomly assigned into Control (n=18), HIBD (n=17) and HBO treatment groups (n=17). HIBD was induced by ligating the left common carotid, followed by 2 hrs hypoxia exposure in the HIBD and HBO treatment groups. The Control group was sham-operated and was not subjected to hypoxia exposure. The HBO therapy with 2 atmosphere absolutes began 0.5-1 hr after HIBD in the HIBD treatment group, once daily for 2 days. The spatial learning and memory ability were evaluated by the Morris water maze test at PD37 to PD41. The morphological and histological changes of the brain, including brain weight, survival neurons, AchE positive unit and NOS positive neurons in hippocampal CA1 region, were detected at PD42. The rats in the HIBD group displayed significant morphological and histological deficits, as well as severe spatial learning and memory disability. In the Morris water maze test, the mean escape latency were longer (56.35 +/- 22.37 s vs 23.07 +/- 16.28 s; P < 0.05) and the probe time and probe length were shorter in the HIBD group (29.29 +/- 6.06 s vs 51.21 +/- 4.59 s and 548 +/- 92 cm vs 989 +/- 101 cm; both P < 0.05) compared with the Control group. The left brain weight in the HIBD group was lighter than that in the Control group (0.601 +/- 0.59 g vs 0.984 +/- 0.18 g; P < 0.05). The survival neurons in the hippocampal CA1 region were less (100 +/- 27/mm vs 183 +/- 8/mm; P < 0.05), as well as the AchE-positive unit and NOS-positive neurons (18.50 +/- 2.24% vs 27.50 +/- 2.18% and 19.25 +/- 4.33 vs 33.75 +/- 5.57 respectively; P < 0.05) after

Adolescents growing up amidst intractable conflict attenuate brain response to pain of outgroup.

PubMed

Levy, Jonathan; Goldstein, Abraham; Influs, Moran; Masalha, Shafiq; Zagoory-Sharon, Orna; Feldman, Ruth

2016-11-29

Adolescents' participation in intergroup conflicts comprises an imminent global risk, and understanding its neural underpinnings may open new perspectives. We assessed Jewish-Israeli and Arab-Palestinian adolescents for brain response to the pain of ingroup/outgroup protagonists using magnetoencephalography (MEG), one-on-one positive and conflictual interactions with an outgroup member, attitudes toward the regional conflict, and oxytocin levels. A neural marker of ingroup bias emerged, expressed via alpha modulations in the somatosensory cortex (S1) that characterized an automatic response to the pain of all protagonists followed by rebound/enhancement to ingroup pain only. Adolescents' hostile social interactions with outgroup members and uncompromising attitudes toward the conflict influenced this neural marker. Furthermore, higher oxytocin levels in the Jewish-Israeli majority and tighter brain-to-brain synchrony among group members in the Arab-Palestinian minority enhanced the neural ingroup bias. Findings suggest that in cases of intractable intergroup conflict, top-down control mechanisms may block the brain's evolutionary-ancient resonance to outgroup pain, pinpointing adolescents' interpersonal and sociocognitive processes as potential targets for intervention.

Brain volume in early MS patients with and without IgG oligoclonal bands in CSF.

PubMed

Fenu, G; Lorefice, L; Sechi, V; Loi, L; Contu, F; Cabras, F; Coghe, G; Frau, J; Secci, M A; Melis, C; Schirru, L; Costa, G; Melas, V; Arru, M; Barracciu, M A; Marrosu, M G; Cocco, E

2018-01-01

Oligoclonal bands of IgG (OB) are proposed as an early prognostic factor of the disease. Growing attention is directed towards brain volume evaluation as a possible marker of the severity of MS. Previous studies found that MS patients lacking OB have less brain atrophy. to evaluate a possible relationship between OB and cerebral volume in a cohort of early MS patients. Inclusion criteria were: diagnosis of relapsing-remitting MS; CSF analysis and MRI acquired simultaneously and within 12 months from clinical onset. A total of 15 healthy controls underwent MRI. In 20 MS patients, CSF analysis did not show OB synthesis (OB negative group). A control group of 25 MS patients in whom OB was detected was also randomly recruited (OB positive group). T test showed a significant difference in NWV between the OB positive and OB negative groups (P value = 0.01), and between the OB positive group and the healthy controls (P value = 0.001). No differences were detected between OB negative group and healthy controls. Multivariable linear regression showed a relationship between NWV and OB synthesis (P value = 0.02) controlling for age, gender, and EDSS. Our preliminary results suggest that OB positive patients show more atrophy of white matter since early phases of the disease, supporting the role of CSF analysis as a prognostic factor in MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Cortical neurons and networks are dormant but fully responsive during isoelectric brain state.

PubMed

Altwegg-Boussac, Tristan; Schramm, Adrien E; Ballestero, Jimena; Grosselin, Fanny; Chavez, Mario; Lecas, Sarah; Baulac, Michel; Naccache, Lionel; Demeret, Sophie; Navarro, Vincent; Mahon, Séverine; Charpier, Stéphane

2017-09-01

A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic

Metastatic brain cancer: prediction of response to whole-brain helical tomotherapy with simultaneous intralesional boost for metastatic disease using quantitative MR imaging features

NASA Astrophysics Data System (ADS)

Sharma, Harish; Bauman, Glenn; Rodrigues, George; Bartha, Robert; Ward, Aaron

2014-03-01

The sequential application of whole brain radiotherapy (WBRT) and more targeted stereotactic radiosurgery (SRS) is frequently used to treat metastatic brain tumors. However, SRS has side effects related to necrosis and edema, and requires separate and relatively invasive localization procedures. Helical tomotherapy (HT) allows for a SRS-type simultaneous infield boost (SIB) of multiple brain metastases, synchronously with WBRT and without separate stereotactic procedures. However, some patients' tumors may not respond to HT+SIB, and would be more appropriately treated with radiosurgery or conventional surgery despite the additional risks and side effects. As a first step toward a broader objective of developing a means for response prediction to HT+SIB, the goal of this study was to investigate whether quantitative measurements of tumor size and appearance (including first- and second-order texture features) on a magnetic resonance imaging (MRI) scan acquired prior to treatment could be used to differentiate responder and nonresponder patient groups after HT+SIB treatment of metastatic disease of the brain. Our results demonstrated that smaller lesions may respond better to this form of therapy; measures of appearance provided limited added value over measures of size for response prediction. With further validation on a larger data set, this approach may lead to a means for prediction of individual patient response based on pre-treatment MRI, supporting appropriate therapy selection for patients with metastatic brain cancer.

Parametric fMRI of paced motor responses uncovers novel whole-brain imaging biomarkers in spinocerebellar ataxia type 3.

PubMed

Duarte, João Valente; Faustino, Ricardo; Lobo, Mercês; Cunha, Gil; Nunes, César; Ferreira, Carlos; Januário, Cristina; Castelo-Branco, Miguel

2016-10-01

Machado-Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole-brain functional biomarkers, based on parametric performance-level-dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel-based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio-paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance-level-based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency-dependent cortico/subcortical activation/deactivation patterns. Cerebellar/cortical rate-dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger-tapping task significantly often reached >80% sensitivity and specificity in single regions-of-interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and/or therapeutic targets in hereditary ataxia. Hum Brain Mapp 37:3656-3668, 2016. © 2016 Wiley

Advanced fiber tracking in early acquired brain injury causing cerebral palsy.

PubMed

Lennartsson, F; Holmström, L; Eliasson, A-C; Flodmark, O; Forssberg, H; Tournier, J-D; Vollmer, B

2015-01-01

Diffusion-weighted MR imaging and fiber tractography can be used to investigate alterations in white matter tracts in patients with early acquired brain lesions and cerebral palsy. Most existing studies have used diffusion tensor tractography, which is limited in areas of complex fiber structures or pathologic processes. We explored a combined normalization and probabilistic fiber-tracking method for more realistic fiber tractography in this patient group. This cross-sectional study included 17 children with unilateral cerebral palsy and 24 typically developing controls. DWI data were collected at 1.5T (45 directions, b=1000 s/mm(2)). Regions of interest were defined on a study-specific fractional anisotropy template and mapped onto subjects for fiber tracking. Probabilistic fiber tracking of the corticospinal tract and thalamic projections to the somatosensory cortex was performed by using constrained spherical deconvolution. Tracts were qualitatively assessed, and DTI parameters were extracted close to and distant from lesions and compared between groups. The corticospinal tract and thalamic projections to the somatosensory cortex were realistically reconstructed in both groups. Structural changes to tracts were seen in the cerebral palsy group and included splits, dislocations, compaction of the tracts, or failure to delineate the tract and were associated with underlying pathology seen on conventional MR imaging. Comparisons of DTI parameters indicated primary and secondary neurodegeneration along the corticospinal tract. Corticospinal tract and thalamic projections to the somatosensory cortex showed dissimilarities in both structural changes and DTI parameters. Our proposed method offers a sensitive means to explore alterations in WM tracts to further understand pathophysiologic changes following early acquired brain injury. © 2015 by American Journal of Neuroradiology.

Reduced brain response to a sweet taste in Hispanic young adults.

PubMed

Szajer, Jacquelyn; Jacobson, Aaron; Green, Erin; Murphy, Claire

2017-11-01

Hispanics have an increased risk for metabolic disorders, which evidence suggests may be due to interactions between lifespan biological, genetic, and lifestyle factors. Studies show the diet of many U.S. Hispanic groups have high sugar consumption, which has been shown to influence future preference for and consumption of high-sugar foods, and is associated with increased risk for insulin-related disorders and obesity. Taste is a primary determinant of food preference and selection. Differences in neural response to taste have been associated with obesity. Understanding brain response to sweet taste stimuli in healthy Hispanic adults is an important first step in characterizing the potential neural mechanisms for this behavior. We used fMRI to examine brain activation during the hedonic evaluation of sucrose as a function of ethnicity in Hispanic and non-Hispanic young adults. Taste stimuli were administered orally while subjects were scanned at 3T. Data were analyzed with AFNI via 3dROIstats and 3dMEMA, a mixed effects multi-level analysis of whole brain activation. The Hispanic group had significantly lower ROI activation in the left amygdala and significantly lower whole brain activation in regions critical for reward processing, and hedonic evaluation (e.g. frontal, orbitofrontal, and anterior cingulate cortices) than the non-Hispanic group. Differences in processing of sweet tastes have important clinical and public health implications, especially considering increased risk of metabolic syndrome and cognitive decline in Hispanic populations. Future research to better understanding relationships between health risk and brain function in Hispanic populations is warranted to better conceptualize and develop interventions for these populations. Copyright © 2017. Published by Elsevier B.V.

Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

PubMed

Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

2016-10-01

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. Copyright © 2016 Elsevier Ltd. All rights

Reinforcement of the Brain's Rich-Club Architecture Following Early Neurodevelopmental Disruption Caused by Very Preterm Birth

PubMed Central

Karolis, Vyacheslav R.; Froudist-Walsh, Sean; Brittain, Philip J.; Kroll, Jasmin; Ball, Gareth; Edwards, A. David; Dell'Acqua, Flavio; Williams, Steven C.; Murray, Robin M.; Nosarti, Chiara

2016-01-01

The second half of pregnancy is a crucial period for the development of structural brain connectivity, and an abrupt interruption of the typical processes of development during this phase caused by the very preterm birth (<33 weeks of gestation) is likely to result in long-lasting consequences. We used structural and diffusion imaging data to reconstruct the brain structural connectome in very preterm-born adults. We assessed its rich-club organization and modularity as 2 characteristics reflecting the capacity to support global and local information exchange, respectively. Our results suggest that the establishment of global connectivity patterns is prioritized over peripheral connectivity following early neurodevelopmental disruption. The very preterm brain exhibited a stronger rich-club architecture than the control brain, despite possessing a relative paucity of white matter resources. Using a simulated lesion approach, we also investigated whether putative structural reorganization takes place in the very preterm brain in order to compensate for its anatomical constraints. We found that connections between the basal ganglia and (pre-) motor regions, as well as connections between subcortical regions, assumed an altered role in the structural connectivity of the very preterm brain, and that such alterations had functional implications for information flow, rule learning, and verbal IQ. PMID:26742566

Do brain responses to emotional images and cigarette cues differ? An fMRI study in smokers

PubMed Central

Versace, Francesco; Engelmann, Jeffrey M.; Jackson, Edward F.; Costa, Vincent D.; Robinson, Jason D.; Lam, Cho Y.; Minnix, Jennifer A.; Brown, Victoria L.; Cinciripini, Paul M.

2011-01-01

Chronic smoking is thought to cause changes in brain reward systems that result in overvaluation of cigarette-related stimuli and undervaluation of natural rewards. We tested the hypotheses that, in smokers, brain circuits involved in emotional processing 1) would be more active during exposure to cigarette-related than neutral pictures, and 2) would be less active to pleasant compared to cigarette-related pictures, suggesting a devaluation of intrinsically pleasant stimuli. We obtained whole brain blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) data from 35 smokers during the presentation of pleasant (erotica and romance), unpleasant (mutilations and sad), neutral, and cigarette-related pictures. Whole brain analyses showed significantly larger BOLD responses during presentation of cigarette-related pictures relative to neutral ones within the secondary visual areas, the cingulate gyrus, the frontal gyrus, the dorsal striatum, and the left insula. BOLD responses to erotic pictures exceeded responses to cigarette-related pictures in all clusters except the insula. Within the left insula we observed larger BOLD responses to cigarette-related pictures than to all other picture categories. By including intrinsically pleasant and unpleasant pictures in addition to neutral ones, we were able to conclude that the presentation of cigarette-related pictures activates brain areas supporting emotional processes, but we did not find evidence of overall reduced activation of the brain reward systems in the presence of intrinsically pleasant stimuli. PMID:22097928

Brain activity and connectivity changes in response to glucose ingestion.

PubMed

van Opstal, A M; Hafkemeijer, A; van den Berg-Huysmans, A A; Hoeksma, M; Blonk, C; Pijl, H; Rombouts, S A R B; van der Grond, J

2018-05-27

The regulatory role of the brain in directing eating behavior becomes increasingly recognized. Although many areas in the brain have been found to respond to food cues, very little data is available after actual caloric intake. The aim of this study was to determine normal whole brain functional responses to ingestion of glucose after an overnight fast. Twenty-five normal weight, adult males underwent functional MRI on two separate visits. In a single-blind randomized study setup, participants received either glucose solution (50 g/300 ml of water) or plain water. We studied changes in Blood Oxygen Level Dependent (BOLD) signal, voxel-based connectivity by Eigenvector Centrality Mapping, and functional network connectivity. Ingestion of glucose led to increased centrality in the thalamus and to decreases in BOLD signal in various brain areas. Decreases in connectivity in the sensory-motor and dorsal visual stream networks were found. Ingestion of water resulted in increased centrality across the brain, and increases in connectivity in the medial and lateral visual cortex network. Increased BOLD intensity was found in the intracalcarine and cingulate cortex. Our data show that ingestion of glucose leads to decreased activity and connectivity in brain areas and networks linked to energy seeking and satiation. In contrast, drinking plain water leads to increased connectivity probably associated with continued food seeking and unfulfilled reward. Trail registration: This study combines data of two studies registered at clinicaltrails.gov under numbers NCT03202342 and NCT03247114.

Multimodal characterization of the semantic N400 response within a rapid evaluation brain vital sign framework.

PubMed

Ghosh Hajra, Sujoy; Liu, Careesa C; Song, Xiaowei; Fickling, Shaun D; Cheung, Teresa P L; D'Arcy, Ryan C N

2018-06-04

For nearly four decades, the N400 has been an important brainwave marker of semantic processing. It can be recorded non-invasively from the scalp using electrical and/or magnetic sensors, but largely within the restricted domain of research laboratories specialized to run specific N400 experiments. However, there is increasing evidence of significant clinical utility for the N400 in neurological evaluation, particularly at the individual level. To enable clinical applications, we recently reported a rapid evaluation framework known as "brain vital signs" that successfully incorporated the N400 response as one of the core components for cognitive function evaluation. The current study characterized the rapidly evoked N400 response to demonstrate that it shares consistent features with traditional N400 responses acquired in research laboratory settings-thereby enabling its translation into brain vital signs applications. Data were collected from 17 healthy individuals using magnetoencephalography (MEG) and electroencephalography (EEG), with analysis of sensor-level effects as well as evaluation of brain sources. Individual-level N400 responses were classified using machine learning to determine the percentage of participants in whom the response was successfully detected. The N400 response was observed in both M/EEG modalities showing significant differences to incongruent versus congruent condition in the expected time range (p < 0.05). Also as expected, N400-related brain activity was observed in the temporal and inferior frontal cortical regions, with typical left-hemispheric asymmetry. Classification robustly confirmed the N400 effect at the individual level with high accuracy (89%), sensitivity (0.88) and specificity (0.90). The brain vital sign N400 characteristics were highly consistent with features of the previously reported N400 responses acquired using traditional laboratory-based experiments. These results provide important evidence supporting

Minimal Brain Dysfunction in Childhood: 1. Outcome in Late Adolescence and Early Adult Years. Final Version.

ERIC Educational Resources Information Center

Milman, Doris H.

Seventy-three patients, diagnosed in childhood as having either maturational lag or organic brain syndrome, were followed for an average of 12 years into late adolescence and early adult life for the purpose of discovering the outcome with respect to ultimate psychiatric status, educational attainment, social adjustment, and global adjustment. At…

Predictive information processing is a fundamental learning mechanism present in early development: evidence from infants.

PubMed

Trainor, Laurel J

2012-02-01

Evidence is presented that predictive coding is fundamental to brain function and present in early infancy. Indeed, mismatch responses to unexpected auditory stimuli are among the earliest robust cortical event-related potential responses, and have been measured in young infants in response to many types of deviation, including in pitch, timing, and melodic pattern. Furthermore, mismatch responses change quickly with specific experience, suggesting that predictive coding reflects a powerful, early-developing learning mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

Culture Modulates the Brain Response to Harmonic Violations: An EEG Study on Hierarchical Syntactic Structure in Music.

PubMed

Akrami, Haleh; Moghimi, Sahar

2017-01-01

We investigated the role of culture in processing hierarchical syntactic structures in music. We examined whether violation of non-local dependencies manifest in event related potentials (ERP) for Western and Iranian excerpts by recording EEG while participants passively listened to sequences of modified/original excerpts. We also investigated oscillatory and synchronization properties of brain responses during processing of hierarchical structures. For the Western excerpt, subjective ratings of conclusiveness were marginally significant and the difference in the ERP components fell short of significance. However, ERP and behavioral results showed that while listening to culturally familiar music, subjects comprehended whether or not the hierarchical syntactic structure was fulfilled. Irregularities in the hierarchical structures of the Iranian excerpt elicited an early negativity in the central regions bilaterally, followed by two later negativities from 450-700 to 750-950 ms. The latter manifested throughout the scalp. Moreover, violations of hierarchical structure in the Iranian excerpt were associated with (i) an early decrease in the long range alpha phase synchronization, (ii) an early increase in the oscillatory activity in the beta band over the central areas, and (iii) a late decrease in the theta band phase synchrony between left anterior and right posterior regions. Results suggest that rhythmic structures and melodic fragments, representative of Iranian music, created a familiar context in which recognition of complex non-local syntactic structures was feasible for Iranian listeners. Processing of neural responses to the Iranian excerpt indicated neural mechanisms for processing of hierarchical syntactic structures in music at different levels of cortical integration.

Face the hierarchy: ERP and oscillatory brain responses in social rank processing.

PubMed

Breton, Audrey; Jerbi, Karim; Henaff, Marie-Anne; Cheylus, Anne; Baudouin, Jean-Yves; Schmitz, Christina; Krolak-Salmon, Pierre; Van der Henst, Jean-Baptiste

2014-01-01

Recognition of social hierarchy is a key feature that helps us navigate through our complex social environment. Neuroimaging studies have identified brain structures involved in the processing of hierarchical stimuli but the precise temporal dynamics of brain activity associated with such processing remains largely unknown. Here, we used electroencephalography to examine the effect of social hierarchy on neural responses elicited by faces. In contrast to previous studies, the key manipulation was that a hierarchical context was constructed, not by varying facial expressions, but by presenting neutral-expression faces in a game setting. Once the performance-based hierarchy was established, participants were presented with high-rank, middle-rank and low-rank player faces and had to evaluate the rank of each face with respect to their own position. Both event-related potentials and task-related oscillatory activity were investigated. Three main findings emerge from the study. First, the experimental manipulation had no effect on the early N170 component, which may suggest that hierarchy did not modulate the structural encoding of neutral-expression faces. Second, hierarchy significantly modulated the amplitude of the late positive potential (LPP) within a 400-700 ms time-window, with more a prominent LPP occurring when the participants processed the face of the highest-rank player. Third, high-rank faces were associated with the highest reduction of alpha power. Taken together these findings provide novel electrophysiological evidence for enhanced allocation of attentional resource in the presence of high-rank faces. At a broader level, this study brings new insights into the neural processing underlying social categorization.

Anti-α4 antibody treatment blocks virus traffic to the brain and gut early, and stabilizes CNS injury late in infection.

PubMed

Campbell, Jennifer H; Ratai, Eva-Maria; Autissier, Patrick; Nolan, David J; Tse, Samantha; Miller, Andrew D; González, R Gilberto; Salemi, Marco; Burdo, Tricia H; Williams, Kenneth C

2014-12-01

Four SIV-infected monkeys with high plasma virus and CNS injury were treated with an anti-α4 blocking antibody (natalizumab) once a week for three weeks beginning on 28 days post-infection (late). Infection in the brain and gut were quantified, and neuronal injury in the CNS was assessed by MR spectroscopy, and compared to controls with AIDS and SIV encephalitis. Treatment resulted in stabilization of ongoing neuronal injury (NAA/Cr by 1H MRS), and decreased numbers of monocytes/macrophages and productive infection (SIV p28+, RNA+) in brain and gut. Antibody treatment of six SIV infected monkeys at the time of infection (early) for 3 weeks blocked monocyte/macrophage traffic and infection in the CNS, and significantly decreased leukocyte traffic and infection in the gut. SIV - RNA and p28 was absent in the CNS and the gut. SIV DNA was undetectable in brains of five of six early treated macaques, but proviral DNA in guts of treated and control animals was equivalent. Early treated animals had low-to-no plasma LPS and sCD163. These results support the notion that monocyte/macrophage traffic late in infection drives neuronal injury and maintains CNS viral reservoirs and lesions. Leukocyte traffic early in infection seeds the CNS with virus and contributes to productive infection in the gut. Leukocyte traffic early contributes to gut pathology, bacterial translocation, and activation of innate immunity.

Early Detection of Increased Intracranial Pressure Episodes in Traumatic Brain Injury: External Validation in an Adult and in a Pediatric Cohort.

PubMed

Güiza, Fabian; Depreitere, Bart; Piper, Ian; Citerio, Giuseppe; Jorens, Philippe G; Maas, Andrew; Schuhmann, Martin U; Lo, Tsz-Yan Milly; Donald, Rob; Jones, Patricia; Maier, Gottlieb; Van den Berghe, Greet; Meyfroidt, Geert

2017-03-01

A model for early detection of episodes of increased intracranial pressure in traumatic brain injury patients has been previously developed and validated based on retrospective adult patient data from the multicenter Brain-IT database. The purpose of the present study is to validate this early detection model in different cohorts of recently treated adult and pediatric traumatic brain injury patients. Prognostic modeling. Noninterventional, observational, retrospective study. The adult validation cohort comprised recent traumatic brain injury patients from San Gerardo Hospital in Monza (n = 50), Leuven University Hospital (n = 26), Antwerp University Hospital (n = 19), Tübingen University Hospital (n = 18), and Southern General Hospital in Glasgow (n = 8). The pediatric validation cohort comprised patients from neurosurgical and intensive care centers in Edinburgh and Newcastle (n = 79). None. The model's performance was evaluated with respect to discrimination, calibration, overall performance, and clinical usefulness. In the recent adult validation cohort, the model retained excellent performance as in the original study. In the pediatric validation cohort, the model retained good discrimination and a positive net benefit, albeit with a performance drop in the remaining criteria. The obtained external validation results confirm the robustness of the model to predict future increased intracranial pressure events 30 minutes in advance, in adult and pediatric traumatic brain injury patients. These results are a large step toward an early warning system for increased intracranial pressure that can be generally applied. Furthermore, the sparseness of this model that uses only two routinely monitored signals as inputs (intracranial pressure and mean arterial blood pressure) is an additional asset.

Maturation of Sensori-Motor Functional Responses in the Preterm Brain.

PubMed

Allievi, Alessandro G; Arichi, Tomoki; Tusor, Nora; Kimpton, Jessica; Arulkumaran, Sophie; Counsell, Serena J; Edwards, A David; Burdet, Etienne

2016-01-01

Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level-dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults. © The Author 2015. Published by Oxford University Press.

Brain glutathione reductase induction increases early survival and decreases lipofuscin accumulation in aging frogs.

PubMed

López-Torres, M; Pérez-Campo, R; Fernandez, A; Barba, C; Barja de Quiroga, G

1993-02-01

Brain catalase was continuously depleted throughout the life span starting with a large population of initially young and old frogs. Free radical-related parameters were measured in the brain tissue once per year after 2.5, 14.5, and 26.5 months of experimentation. Brain lipofuscin accumulation was observed after 14.5 and 26.5 months, and survival was continuously followed during 33 months. The age of the animal did not decrease endogenous antioxidants nor increase tissue peroxidation either in cross-sectional or longitudinal comparisons. Continuous catalase depletion similarly affected young and old animals, inducing glutathione reductase, tending to decrease oxidized glutathione/reduced glutathione (GSSG/GSH) ratio, decreasing lipofuscin accumulation in the brain, and increasing survival from 46% to 91% after 14.5 months. At 26.5 months of experimentation the loss of the glutathione reductase induction in catalase-depleted animals was accompanied by the presence of higher lipofuscin deposits than in controls and was followed by a great increase in mortality rate. Even though the maximal life span (7 years) was the same in the control and treated animals which were already old (4.2 years) at the beginning of the experiment, the treated animals showed a strong reduction in the rates of early death. It is proposed that the maintenance of a high antioxidant/prooxidant balance in the vertebrate brain greatly increases the probability of the individual to reach the final segments of its species-specific life span.

APPROACHING THE BIOLOGY OF HUMAN PARENTAL ATTACHMENT: BRAIN IMAGING, OXYTOCIN AND COORDINATED ASSESSMENTS OF MOTHERS AND FATHERS

PubMed Central

Swain, JE; Kim, P; Spicer, J; Ho, SS; Dayton, CJ; Elmadih, A; Abel, KM

2014-01-01

Brain networks that govern parental response to infant signals have been studied with imaging techniques over the last 15 years. The complex interaction of thoughts and behaviors required for sensitive parenting of offspring enable formation of each individual’s first social bonds and critically shape infants’ behavior. This review concentrates on magnetic resonance imaging experiments which directly examine the brain systems involved in parental responses to infant cues. First, we introduce themes in the literature on parental brain circuits studied to date. Next, we present a thorough chronological review of state-of-the-art fMRI studies that probe the parental brain with a range of baby audio and visual stimuli. We also highlight the putative role of oxytocin and effects of psychopathology, as well as the most recent work on the paternal brain. Taken together, a new model emerges in which we propose that cortico-limbic networks interact to support parental brain responses to infants for arousal/salience/motivation/reward, reflexive/instrumental caring, emotion response/regulation and integrative/complex cognitive processing. Maternal sensitivity and the quality of caregiving behavior are likely determined by the responsiveness of these circuits toward long-term influence of early-life experiences on offspring. The function of these circuits is modifiable by current and early-life experiences, hormonal and other factors. Known deviation from the range of normal function in these systems is particularly associated with (maternal) mental illnesses – commonly, depression and anxiety, but also schizophrenia and bipolar disorder. Finally, we discuss the limits and extent to which brain imaging may broaden our understanding of the parental brain, and consider a current model and future directions that may have profound implications for intervention long term outcomes in families across risk and resilience profiles. PMID:24637261

Surprise responses in the human brain demonstrate statistical learning under high concurrent cognitive demand

NASA Astrophysics Data System (ADS)

Garrido, Marta Isabel; Teng, Chee Leong James; Taylor, Jeremy Alexander; Rowe, Elise Genevieve; Mattingley, Jason Brett

2016-06-01

The ability to learn about regularities in the environment and to make predictions about future events is fundamental for adaptive behaviour. We have previously shown that people can implicitly encode statistical regularities and detect violations therein, as reflected in neuronal responses to unpredictable events that carry a unique prediction error signature. In the real world, however, learning about regularities will often occur in the context of competing cognitive demands. Here we asked whether learning of statistical regularities is modulated by concurrent cognitive load. We compared electroencephalographic metrics associated with responses to pure-tone sounds with frequencies sampled from narrow or wide Gaussian distributions. We showed that outliers evoked a larger response than those in the centre of the stimulus distribution (i.e., an effect of surprise) and that this difference was greater for physically identical outliers in the narrow than in the broad distribution. These results demonstrate an early neurophysiological marker of the brain's ability to implicitly encode complex statistical structure in the environment. Moreover, we manipulated concurrent cognitive load by having participants perform a visual working memory task while listening to these streams of sounds. We again observed greater prediction error responses in the narrower distribution under both low and high cognitive load. Furthermore, there was no reliable reduction in prediction error magnitude under high-relative to low-cognitive load. Our findings suggest that statistical learning is not a capacity limited process, and that it proceeds automatically even when cognitive resources are taxed by concurrent demands.

The levels of the GluN2A NMDA receptor subunit are modified in both the neonatal and adult rat brain by an early experience involving denial of maternal contact.

PubMed

Manatos, V; Stylianopoulou, F; Stamatakis, A

2016-01-26

The composition of the N-methyl-d-aspartate receptor receptor in GluN2A/GluN2B subunits is important in determining its characteristics and its role in plasticity, a property of the brain which is known to be critically affected by early experiences. In the present work we employed an early experience model involving either receipt (RER) or denial (DER) of the expected reward of maternal contact within the context of learning by the pups of a T-maze on postnatal days (PND) 10-13. We investigated the effects of the RER and DER early experiences on GluN1, GluN2A and GluN2B levels in the prefrontal cortex (PFC), hippocampus and amygdala of the rat. We show that on PND13 the DER animals had lower GluN2A levels in the PFC. In adulthood DER males had higher GluN2A levels in the hippocampus, both under basal conditions and after exposure to a novel environment. The early experiences did not affect the response to the novelty. After exposure to a novel environment animals of all three groups (DER, RER, Control) responded with an increase in GluN2A levels in the brain areas examined. We did not detect any effects on GluN1 or GluN2B levels. The alterations in GluN2A levels observed in the DER animals could in part be responsible for their behavioral phenotype, described previously, which includes an increased susceptibility for the expression of depressive-like behavior. Copyright © 2015. Published by Elsevier Ireland Ltd.

Brain region-specific gene expression changes after chronic intermittent ethanol exposure and early withdrawal in C57BL/6J mice

PubMed Central

Melendez, Roberto I.; McGinty, Jacqueline F.; Kalivas, Peter W.; Becker, Howard C.

2014-01-01

Neuroadaptations that participate in the ontogeny of alcohol dependence are likely a result of altered gene expression in various brain regions. The present study investigated brain region-specific changes in the pattern and magnitude of gene expression immediately following chronic intermittent ethanol (CIE) exposure and 8 hours following final ethanol exposure [i.e. early withdrawal (EWD)]. High-density oligonucleotide microarrays (Affymetrix 430A 2.0, Affymetrix, Santa Clara, CA, USA) and bioinformatics analysis were used to characterize gene expression and function in the prefrontal cortex (PFC), hippocampus (HPC) and nucleus accumbens (NAc) of C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME, USA). Gene expression levels were determined using gene chip robust multi-array average followed by statistical analysis of microarrays and validated by quantitative real-time reverse transcription polymerase chain reaction and Western blot analysis. Results indicated that immediately following CIE exposure, changes in gene expression were strikingly greater in the PFC (284 genes) compared with the HPC (16 genes) and NAc (32 genes). Bioinformatics analysis revealed that most of the transcriptionally responsive genes in the PFC were involved in Ras/MAPK signaling, notch signaling or ubiquitination. In contrast, during EWD, changes in gene expression were greatest in the HPC (139 genes) compared with the PFC (four genes) and NAc (eight genes). The most transcriptionally responsive genes in the HPC were involved in mRNA processing or actin dynamics. Of the few genes detected in the NAc, the most representatives were involved in circadian rhythms. Overall, these findings indicate that brain region-specific and time-dependent neuroadaptive alterations in gene expression play an integral role in the development of alcohol dependence and withdrawal. PMID:21812870

An Experimental Brain Missile Wound: Ascertaining Pathophysiology and evaluating Treatments to Lower Mortality and Morbidity

DTIC Science & Technology

1989-04-27

Narayan R, et al: Early insults to the injured brain. JAMA 240:439-442, 1978. 91 Neubauer JA, and Edelman N: Nonuniform brain blood flow response to...Research ( LAIR ), Bldg. 1110 ATI7I: SGRD-ULZ-RC Presidio of San Francisco, CA 94129-6815 1 copy Comander US Army Medical Research and Develop mnt Coand

Residual brain injury after early discontinuation of cooling therapy in mild neonatal encephalopathy.

PubMed

Lally, Peter J; Montaldo, Paolo; Oliveira, Vânia; Swamy, Ravi Shankar; Soe, Aung; Shankaran, Seetha; Thayyil, Sudhin

2018-07-01

We examined the brain injury and neurodevelopmental outcomes in a prospective cohort of 10 babies with mild encephalopathy who had early cessation of cooling therapy. All babies had MRI and spectroscopy within 2 weeks after birth and neurodevelopmental assessment at 2 years. Cooling was prematurely discontinued at a median age of 9 hours (IQR 5-13) due to rapid clinical improvement. Five (50%) had injury on MRI or spectroscopy, and two (20%) had an abnormal neurodevelopmental outcome at 2 years. Premature cessation of cooling therapy in babies with mild neonatal encephalopathy does not exclude residual brain injury and adverse long-term neurodevelopmental outcomes. This study refers to babies recruited into the MARBLE study (NCT01309711, pre-results stage). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Tunicamycin-induced unfolded protein response in the developing mouse brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Haiping; Wang, Xin; Ke, Zun-Ji

Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident bymore » the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific.« less

The developmental disruptions of serotonin signaling may involved in autism during early brain development.