Self-reference, emotion inhibition and somatosensory disturbance: preliminary investigation of network perturbations in conversion disorder.

PubMed

Monsa, R; Peer, M; Arzy, S

2018-06-01

Conversion disorder (CD), or functional neurological disorder, is manifested as a neurological disturbance that is not macroscopically visible on clinical structural neuroimaging and is instead ascribed to underlying psychological stress. Known for many years in neuropsychiatry, a comprehensive explanation of the way in which psychological stress leads to a neurological deficit of a structural-like origin is still lacking. We applied whole-brain network-based data-driven analyses on resting-state functional magnetic resonance imaging, recorded in seven patients with acute-onset, stroke-like CD with unilateral paresis and hypoesthesia as compared with 15 age-matched healthy controls. We used a clustering analysis to measure functional connectivity (FC) strength within 10 different brain networks, as well as between these networks. Finally, we tested FC of specific brain regions that are known to be involved in CD. We found a significant increase in FC strength only within the default-mode network (DMN), which manages self-referential processing. Examination of inter-connectivity between networks showed a structure of disturbed connectivity, which included decreased connectivity between the DMN and limbic/salience network, increased connectivity between the limbic/salience network and body-related temporo-parieto-occipital junction network, decreased connectivity between the temporo-parieto-occipital junction and memory-related medial temporal lobe, and decreased connectivity between the medial temporal lobe and sensorimotor network. Region-specific FC analysis showed increased connectivity between the hippocampus and DMN. These preliminary results of disturbances in brain networks related to memory, emotions and self-referential processing, and networks involved in motor planning and execution, suggest a role of these cognitive functions in the psychopathology of CD. © 2018 EAN.

Abnormal Functional MRI BOLD Contrast in the Vegetative State after Severe Traumatic Brain Injury

ERIC Educational Resources Information Center

Heelmann, Volker

2010-01-01

For the rehabilitation process, the treatment of patients surviving brain injury in a vegetative state is still a serious challenge. The aim of this study was to investigate patients exhibiting severely disturbed consciousness using functional magnetic resonance imaging. Five cases of posttraumatic vegetative state and one with minimal…

Systemic Analysis of Brain Mechanisms Underlying Learning Disabilities: An Introduction to the Brain Behavior Relationship.

ERIC Educational Resources Information Center

Scaramella-Nowinski, Valerie L.

The paper presents a discussion of human mental processes as they relate to learning disabilities. Pathognomonic symptoms associated with disturbances to brain areas or functional systems are discussed, as well as treatment procedures. This brain behavior relationship is offered as a basis for a classification system that is seen to more clearly…

BDNF in fragile X syndrome.

PubMed

Castrén, Maija L; Castrén, Eero

2014-01-01

Fragile X syndrome (FXS) is a monogenic disorder that is caused by the absence of FMR1 protein (FMRP). FXS serves as an excellent model disorder for studies investigating disturbed molecular mechanisms and synapse function underlying cognitive impairment, autism, and behavioral disturbance. Abnormalities in dendritic spines and synaptic transmission in the brain of FXS individuals and mouse models for FXS indicate perturbations in the development, maintenance, and plasticity of neuronal network connectivity. However, numerous alterations are found during the early development in FXS, including abnormal differentiation of neural progenitors and impaired migration of newly born neurons. Several aspects of FMRP function are modulated by brain-derived neurotrophic factor (BDNF) signaling. Here, we review the evidence of the role for BDNF in the developing and adult FXS brain. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Quantitative evaluation of visual gnosis in children with focal brain lesions].

PubMed

Pencheva, S; Zaprianova, L

1983-01-01

Bearing in mind the opinion of many authors on a great plasticity and interchangeability of the brain cortical functional systems in children the authors have carried out an experiment with 40 children with focal damages of the brain hemispheres, in 20 of whom the right, and in the other 20 the left hemisphere was affected. Use was made of the method of visual gnosis quantitative assessment in the modification of Pencheva and Mavlov (1975). In the children with the focal damages, more or less marked disturbances of the visual gnosis were revealed, however, no statistically significant relationship between the disturbances and the brain side were disclosed. The agnostic disorders were equally frequent in the children of both groups.

Symptom clusters in patients with high-grade glioma.

PubMed

Fox, Sherry W; Lyon, Debra; Farace, Elana

2007-01-01

To describe the co-occurring symptoms (depression, fatigue, pain, sleep disturbance, and cognitive impairment), quality of life (QoL), and functional status in patients with high-grade glioma. Correlational, descriptive study of 73 participants with high-grade glioma in the U.S. Nine brief measures were obtained with a mailed survey. Participants were recruited from the online message board of The Healing Exchange BRAIN TRUST, a nonprofit organization dedicated to improving quality of life for people with brain tumors. Two symptom cluster models were examined. Four co-occurring symptoms were significantly correlated with each other and explained 29% of the variance in QoL: depression, fatigue, sleep disturbance, and cognitive impairment. Depression, fatigue, sleep disturbance, cognitive impairment, and pain were significantly correlated with each other and explained 62% of the variance in functional status. The interrelationships of the symptoms examined in this study and their relationships with QoL and functional status meet the criteria for defining a symptom cluster. The differences in the models of QoL and functional status indicates that symptom clusters may have unique characteristics in patients with gliomas.

Interaction between lexical and grammatical language systems in the brain

NASA Astrophysics Data System (ADS)

Ardila, Alfredo

2012-06-01

This review concentrates on two different language dimensions: lexical/semantic and grammatical. This distinction between a lexical/semantic system and a grammatical system is well known in linguistics, but in cognitive neurosciences it has been obscured by the assumption that there are several forms of language disturbances associated with focal brain damage and hence language includes a diversity of functions (phoneme discrimination, lexical memory, grammar, repetition, language initiation ability, etc.), each one associated with the activity of a specific brain area. The clinical observation of patients with cerebral pathology shows that there are indeed only two different forms of language disturbances (disturbances in the lexical/semantic system and disturbances in the grammatical system); these two language dimensions are supported by different brain areas (temporal and frontal) in the left hemisphere. Furthermore, these two aspects of the language are developed at different ages during child's language acquisition, and they probably appeared at different historical moments during human evolution. Mechanisms of learning are different for both language systems: whereas the lexical/semantic knowledge is based in a declarative memory, grammatical knowledge corresponds to a procedural type of memory. Recognizing these two language dimensions can be crucial in understanding language evolution and human cognition.

Disturbed prefrontal and temporal brain function during emotion and cognition interaction in criminal psychopathy.

PubMed

Müller, Jürgen L; Sommer, Monika; Döhnel, Katrin; Weber, Tatjana; Schmidt-Wilcke, Tobias; Hajak, Göran

2008-01-01

Impaired emotional responsiveness has been revealed as a hallmark of psychopathy. In spite of an increasing database on emotion processing, studies on cognitive function and in particular on the impact of emotion on cognition in psychopathy are rare. We used pictures from the International Affective Picture Set (IAPS) and a Simon Paradigm to address emotion-cognition interaction while functional and structural imaging data were obtained in 12 healthy controls and 10 psychopaths. We found an impaired emotion-cognition interaction in psychopaths that correlated with a changed prefrontal and temporal brain activation. With regard to the temporal cortex, it is shown that structure and function of the right superior temporal gyrus is disturbed in psychopathy, supporting a neurobiological approach to psychopathy, in which structure and function of the right STG may be important. (c) 2008 John Wiley & Sons, Ltd.

Correction of biochemical and functional disorders in brain ischaemia with laser therapy

NASA Astrophysics Data System (ADS)

Musienko, Julia I.; Nechipurenko, Natalia I.; Vasilevskaya, Ludmila A.

2005-08-01

Application of intravenous laser irradiation of blood (ILIB) is considered to be the most effective method of laser therapy and its application is expedient pathogenetically in the ischemic disturbances. The aim of this study is to investigate ILIB influence with red helium-neon laser (HNL) with 630 nm wavelength and different powers on blood oxygen transport (BOT), cerebral and dermal microhaemodynamics (MGD), hydro-ion balance in normal rabbits and after modeling of local ischemia of brain (LIB). Experimental cerebral ischemia is characterized by development of BOT disturbance, ionic disbalance and edema in the ischemic brain region. Microcirculation disturbances with worsening of the cerebral and dermal MHD were revealed. ILIB with HNL radiation of 2.5 and 4.5 mW powers provokes dehydratation of brain structure alone with the K+, Na+ concentration decreasing and hemoglobin-oxygen affinity increasing in intact group of animals. There was not revealed marked changes of cerebral MHD condition here. Using of ILIB in rabbits after LIB contributes for improving function of BOT, normalizing of water content in all cerebral structures compared to operated animals. Preventive ILIB provoked improvement of speckl-optical parameters and marked protective effect on microhaemodynamics processes in superficial brain structures. HNL radiation with 1.0 mW power results in worsening of oxygen transport, cerebral and skin MHD, hydro-ion homeostasis in animals with LIB modeling. Thus, laser haemotherapy contributes for improving of hydro-ion status, blood oxygen transport and cerebral microcirculation in brain ischemia, what allows considering that helium-neon radiation with the pointed regimen is substantiated pathogenetically in brain ischaemia.

The Functional Classification of Brain Damage-Related Vision Loss

ERIC Educational Resources Information Center

Colenbrander, August

2009-01-01

This article provides a terminological framework to show the relationships among different types of visual deficits. It distinguishes between visual functions, which describe how the eye and the lower visual system function, and functional vision, which describes how a person functions. When visual functions are disturbed, the term "visual…

Neurodevelopment in children with intrauterine growth restriction: adverse effects and interventions.

PubMed

Wang, Yan; Fu, Wei; Liu, Jing

2016-01-01

Intrauterine growth restriction (IUGR) is associated with higher rates of fetal, perinatal, and neonatal morbidity and mortality. The consequences of IUGR include short-term metabolic, hematological and thermal disturbances that lead to metabolic syndrome in children and adults. Additionally, IUGR severely affects short- and long-term fetal brain development and brain function (including motor, cognitive and executive function) and neurobehavior, especially neuropsychology. This review details the adverse effects of IUGR on fetal brain development and discusses intervention strategies.

The Developmental Course of Sleep Disturbances Across Childhood Relates to Brain Morphology at Age 7: The Generation R Study.

PubMed

Kocevska, Desana; Muetzel, Ryan L; Luik, Annemarie I; Luijk, Maartje P C M; Jaddoe, Vincent W; Verhulst, Frank C; White, Tonya; Tiemeier, Henning

2017-01-01

Little is known about the impact of sleep disturbances on the structural properties of the developing brain. This study explored associations between childhood sleep disturbances and brain morphology at 7 years. Mothers from the Generation R cohort reported sleep disturbances in 720 children at ages 2 months, 1.5, 2, 3, and 6 years. T1-weighted Magnetic Resonance Imaging (MRI) images were used to assess brain structure at 7 years. Associations of sleep disturbances at each age and of sleep disturbance trajectories with brain volumes (total brain volume, cortical and subcortical grey matter, white matter) were tested with linear regressions. To assess regional differences, sleep disturbance trajectories were tested as determinants for cortical thickness in whole-brain analyses. Sleep disturbances followed a declining trend from toddlerhood onwards. Infant sleep was not associated with brain morphology at age 7. Per SD sleep disturbances (one frequent symptom or two less frequent symptoms) at 2 and 3 years of age, children had -6.3 (-11.7 to -0.8) cm3 and -6.4 (-11.7 to -1.7) cm3 smaller grey matter volumes, respectively. Sleep disturbances at age 6 years were associated with global brain morphology (grey matter: -7.3 (-12.1 to -2.6), p value = .01). Consistently, trajectory analyses showed that more adverse developmental course of childhood sleep disturbances are associated with smaller grey matter volumes and thinner dorsolateral prefrontal cortex. Sleep disturbances from age 2 years onwards are associated with smaller grey matter volumes. Thinner prefrontal cortex in children with adverse sleep disturbance trajectories may reflect effects of sleep disturbances on brain maturation. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Balance Deficit and Brain Connectivity in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Kim, Sun Mi; Hyun, Gi Jung; Jung, Tae-Woon; Son, Young Don; Cho, In-Hee; Kee, Baik Seok; Han, Doug Hyun

2017-07-01

We aimed to assess disturbances in postural and gait balance and functional connectivity within the brain regions controlling balance in children with attention-deficit/hyperactivity disorder (ADHD). Thirteen children with ADHD and 13 age- and sex-matched controls were recruited. Gait balance was assessed by the difference in the center of pressure (COP) between the left and right foot, as well as the difference in plantar pressure between the left and right foot during gait. Neuroimaging data were acquired using a 3.0 Tesla MRI scanner. Functional connectivity between the vermis of the cerebellum and all other brain regionswas assessed. The difference in plantar pressure between the left foot and right foot in the ADHD group was greater than that observed in the control group. The average COP jerk score of the right foot in the ADHD group was higher than that observed in the control group. A higher functional connectivity between the cerebellum and the right middle frontal gyrus (premotor cortex) and medial frontal gyrus (cingulate gyrus) was observed in the control group relative to the ADHD group. In the ADHD group, the difference in plantar pressure between the left and right foot was also negatively correlated with the beta-value within the middle frontal gyrus. Children with ADHD had disturbance of balance as assessed by plantar pressure. Decreased brain connectivity from the cerebellum to the premotor cortex and anterior cingulate was associated with disturbances of posture and balance in children with ADHD.

Interrelation between Neuroendocrine Disturbances and Medical Complications Encountered during Rehabilitation after TBI

PubMed Central

Renner, Caroline I. E.

2015-01-01

Traumatic brain injury is not a discrete event but an unfolding sequence of damage to the central nervous system. Not only the acute phase but also the subacute and chronic period after injury, i.e., during inpatient rehabilitation, is characterized by multiple neurotransmitter alterations, cellular dysfunction, and medical complications causing additional secondary injury. Neuroendocrine disturbances also influence neurological outcome and are easily overlooked as they often present with diffuse symptoms such as fatigue, depression, poor concentration, or a decline in overall cognitive function; these are also typical sequelae of traumatic brain injury. Furthermore, neurological complications such as hydrocephalus, epilepsy, fatigue, disorders of consciousness, paroxysmal sympathetic hyperactivity, or psychiatric-behavioural symptoms may mask and/or complicate the diagnosis of neuroendocrine disturbances, delay appropriate treatment and impede neurorehabilitation. The present review seeks to examine the interrelation between neuroendocrine disturbances with neurological complications frequently encountered after moderate to severe TBI during rehabilitation. Common neuroendocrine disturbances and medical complications and their clinical implications are discussed. PMID:26402710

Connectomic disturbances in attention-deficit/hyperactivity disorder: a whole-brain tractography analysis.

PubMed

Hong, Soon-Beom; Zalesky, Andrew; Fornito, Alex; Park, Subin; Yang, Young-Hui; Park, Min-Hyeon; Song, In-Chan; Sohn, Chul-Ho; Shin, Min-Sup; Kim, Bung-Nyun; Cho, Soo-Churl; Han, Doug Hyun; Cheong, Jae Hoon; Kim, Jae-Won

2014-10-15

Few studies have sought to identify, in a regionally unbiased way, the precise cortical and subcortical regions that are affected by white matter abnormalities in attention-deficit/hyperactivity disorder (ADHD). This study aimed to derive a comprehensive, whole-brain characterization of connectomic disturbances in ADHD. Using diffusion tensor imaging, whole-brain tractography, and an imaging connectomics approach, we characterized altered white matter connectivity in 71 children and adolescents with ADHD compared with 26 healthy control subjects. White matter differences were further delineated between patients with (n = 40) and without (n = 26) the predominantly hyperactive/impulsive subtype of ADHD. A significant network comprising 25 distinct fiber bundles linking 23 different brain regions spanning frontal, striatal, and cerebellar brain regions showed altered white matter structure in ADHD patients (p < .05, family-wise error-corrected). Moreover, fractional anisotropy in some of these fiber bundles correlated with attentional disturbances. Attention-deficit/hyperactivity disorder subtypes were differentiated by a right-lateralized network (p < .05, family-wise error-corrected) predominantly linking frontal, cingulate, and supplementary motor areas. Fractional anisotropy in this network was also correlated with continuous performance test scores. Using an unbiased, whole-brain, data-driven approach, we demonstrated abnormal white matter connectivity in ADHD. The correlations observed with measures of attentional performance underscore the functional importance of these connectomic disturbances for the clinical phenotype of ADHD. A distributed pattern of white matter microstructural integrity separately involving frontal, striatal, and cerebellar brain regions, rather than direct frontostriatal connectivity, appears to be disrupted in children and adolescents with ADHD. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Structural Connectivity Relates to Perinatal Factors and Functional Impairment at 7 Years in Children Born Very Preterm

PubMed Central

Thompson, Deanne K.; Chen, Jian; Beare, Richard; Adamson, Christopher L.; Ellis, Rachel; Ahmadzai, Zohra M.; Kelly, Claire E.; Lee, Katherine J.; Zalesky, Andrew; Yang, Joseph Y.M.; Hunt, Rodney W.; Cheong, Jeanie L.Y.; Inder, Terrie E.; Doyle, Lex W.; Seal, Marc L.; Anderson, Peter J.

2016-01-01

Objective To use structural connectivity to (1) compare brain networks between typically and atypically developing (very preterm) children, (2) explore associations between potential perinatal developmental disturbances and brain networks, and (3) describe associations between brain networks and functional impairments in very preterm children. Methods 26 full-term and 107 very preterm 7-year-old children (born <30 weeks’ gestational age and/or <1250 g) underwent T1- and diffusion-weighted imaging. Global white matter fiber networks were produced using 80 cortical and subcortical nodes, and edges created using constrained spherical deconvolution-based tractography. Global graph theory metrics were analysed, and regional networks were identified using network-based statistics. Cognitive and motor function were assessed at 7 years of age. Results Compared with full-term children, very preterm children had reduced density, lower global efficiency and higher local efficiency. Those with lower gestational age at birth, infection or higher neonatal brain abnormality score had reduced connectivity. Reduced connectivity within a widespread network was predictive of impaired IQ, while reduced connectivity within the right parietal and temporal lobes was associated with motor impairment in very preterm children. Conclusions This study utilized an innovative structural connectivity pipeline to reveal that children born very preterm have less connected and less complex brain networks compared with typically developing term-born children. Adverse perinatal factors led to disturbances in white matter connectivity, which in turn are associated with impaired functional outcomes, highlighting novel structure-function relationships. PMID:27046108

Optimization of choline administration regimen for correction of cognitive functions in rats after brain injury.

PubMed

Guseva, M V; Kamenskii, A A; Gusev, V B

2013-06-01

Choline diet promotes improvement of the brain cognitive functions in rats with moderate-to-severe traumatic brain injury. In previous studies, the rats received choline being standard (0.2%) or choline-supplemented (2%) diet for 2 weeks prior to and 2 weeks after experimental brain injury. To the end of the experiments (in 4 weeks), the post-traumatic disturbances in the cognitive functions were observed in both groups, although they were less pronounced than in the rats kept on the choline-supplemented diet. Based on original mathematical model, this paper proposes a method to calculate the most efficient use of choline to correct the brain cognitive functions. In addition to evaluating the cognitive functions, the study assessed expression of α7 nicotinic acetylcholine receptors, the amount of consumed food and water, and the dynamics of body weight.

Whole-brain structural topology in adult attention-deficit/hyperactivity disorder: Preserved global - disturbed local network organization.

PubMed

Sidlauskaite, Justina; Caeyenberghs, Karen; Sonuga-Barke, Edmund; Roeyers, Herbert; Wiersema, Jan R

2015-01-01

Prior studies demonstrate altered organization of functional brain networks in attention-deficit/hyperactivity disorder (ADHD). However, the structural underpinnings of these functional disturbances are poorly understood. In the current study, we applied a graph-theoretic approach to whole-brain diffusion magnetic resonance imaging data to investigate the organization of structural brain networks in adults with ADHD and unaffected controls using deterministic fiber tractography. Groups did not differ in terms of global network metrics - small-worldness, global efficiency and clustering coefficient. However, there were widespread ADHD-related effects at the nodal level in relation to local efficiency and clustering. The affected nodes included superior occipital, supramarginal, superior temporal, inferior parietal, angular and inferior frontal gyri, as well as putamen, thalamus and posterior cerebellum. Lower local efficiency of left superior temporal and supramarginal gyri was associated with higher ADHD symptom scores. Also greater local clustering of right putamen and lower local clustering of left supramarginal gyrus correlated with ADHD symptom severity. Overall, the findings indicate preserved global but altered local network organization in adult ADHD implicating regions underpinning putative ADHD-related neuropsychological deficits.

Compensation through Functional Hyperconnectivity: A Longitudinal Connectome Assessment of Mild Traumatic Brain Injury

PubMed Central

Iraji, Armin; Chen, Hanbo; Wiseman, Natalie; Welch, Robert D.; O'Neil, Brian J.; Haacke, E. Mark; Liu, Tianming; Kou, Zhifeng

2016-01-01

Mild traumatic brain injury (mTBI) is a major public health concern. Functional MRI has reported alterations in several brain networks following mTBI. However, the connectome-scale brain network changes are still unknown. In this study, sixteen mTBI patients were prospectively recruited from an emergency department and followed up at 4–6 weeks after injury. Twenty-four healthy controls were also scanned twice with the same time interval. Three hundred fifty-eight brain landmarks that preserve structural and functional correspondence of brain networks across individuals were used to investigate longitudinal brain connectivity. Network-based statistic (NBS) analysis did not find significant difference in the group-by-time interaction and time effects. However, 258 functional pairs show group differences in which mTBI patients have higher functional connectivity. Meta-analysis showed that “Action” and “Cognition” are the most affected functional domains. Categorization of connectomic signatures using multiview group-wise cluster analysis identified two patterns of functional hyperconnectivity among mTBI patients: (I) between the posterior cingulate cortex and the association areas of the brain and (II) between the occipital and the frontal lobes of the brain. Our results demonstrate that brain concussion renders connectome-scale brain network connectivity changes, and the brain tends to be hyperactivated to compensate the pathophysiological disturbances. PMID:26819765

Compensation through Functional Hyperconnectivity: A Longitudinal Connectome Assessment of Mild Traumatic Brain Injury.

PubMed

Iraji, Armin; Chen, Hanbo; Wiseman, Natalie; Welch, Robert D; O'Neil, Brian J; Haacke, E Mark; Liu, Tianming; Kou, Zhifeng

2016-01-01

Mild traumatic brain injury (mTBI) is a major public health concern. Functional MRI has reported alterations in several brain networks following mTBI. However, the connectome-scale brain network changes are still unknown. In this study, sixteen mTBI patients were prospectively recruited from an emergency department and followed up at 4-6 weeks after injury. Twenty-four healthy controls were also scanned twice with the same time interval. Three hundred fifty-eight brain landmarks that preserve structural and functional correspondence of brain networks across individuals were used to investigate longitudinal brain connectivity. Network-based statistic (NBS) analysis did not find significant difference in the group-by-time interaction and time effects. However, 258 functional pairs show group differences in which mTBI patients have higher functional connectivity. Meta-analysis showed that "Action" and "Cognition" are the most affected functional domains. Categorization of connectomic signatures using multiview group-wise cluster analysis identified two patterns of functional hyperconnectivity among mTBI patients: (I) between the posterior cingulate cortex and the association areas of the brain and (II) between the occipital and the frontal lobes of the brain. Our results demonstrate that brain concussion renders connectome-scale brain network connectivity changes, and the brain tends to be hyperactivated to compensate the pathophysiological disturbances.

[Traumatic brain injuries--forensic and expertise aspects].

PubMed

Vuleković, Petar; Simić, Milan; Misić-Pavkov, Gordana; Cigić, Tomislav; Kojadinović, Zeljko; Dilvesi, Dula

2008-01-01

Traumatic brain injuries have major socio-economic importance due to their frequency, high mortality and serious consequences. According to their nature the consequences of these injuries may be classified as neurological, psychiatric and esthetic. Various lesions of brain structures cause neurological consequences such as disturbance of motor functions, sensibility, coordination or involuntary movements, speech disturbances and other deviations, as well as epilepsy. Psychiatric consequences include cognitive deficit, emotional disturbances and behavior disturbances. CRIMINAL-LEGAL ASPECT OF TRAUMATIC BRAIN INJURIES AND LITIGATION: Criminal-legal aspect of traumatic brain injuries expertise understands the qualification of these injuries as mild, serious and qualified serious body injuries as well as the expertise about the mechanisms of their occurrence. Litigation expertise includes the estimation of pain, fear, diminished, i.e. lost vital activity and disability, esthetic marring, and psychological suffer based on the diminished general vital activity and esthetic marring. Evaluation of consequences of traumatic brain injuries should be performed only when it can be positively confirmed that they are permanent, i.e. at least one year after the injury. Expertise of these injuries is interdisciplinary. Among clinical doctors the most competent medical expert is the one who is in charge for diagnostics and injury treatment, with the recommendation to avoid, if possible, the doctor who conducted treatment. For the estimation of general vital activity, the neurological consequences, pain and esthetic marring expertise, the most competent doctors are neurosurgeon and neurologist. Psychological psychiatric consequences and fear expertise have to be performed by the psychiatrist. Specialists of forensic medicine contribute with knowledge of criminal low and legal expertise.

Aberrant brain stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer's disease.

PubMed

Lee, Ji Han; Jung, Won Sang; Choi, Woo Hee; Lim, Hyun Kook

2016-01-01

Among patients with Alzheimer's disease (AD), sleep disturbances are common and serious noncognitive symptoms. Previous studies of AD patients have identified deformations in the brain stem, which may play an important role in the regulation of sleep. The aim of this study was to further investigate the relationship between sleep disturbances and alterations in brain stem morphology in AD. In 44 patients with AD and 40 healthy elderly controls, sleep disturbances were measured using the Neuropsychiatry Inventory sleep subscale. We employed magnetic resonance imaging-based automated segmentation tools to examine the relationship between sleep disturbances and changes in brain stem morphology. Analyses of the data from AD subjects revealed significant correlations between the Neuropsychiatry Inventory sleep-subscale scores and structural alterations in the left posterior lateral region of the brain stem, as well as normalized brain stem volumes. In addition, significant group differences in posterior brain stem morphology were observed between the AD group and the control group. This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD. In line with previous findings, this study lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD. Further longitudinal research is needed to confirm these findings.

The role of lateral habenula-dorsal raphe nucleus circuits in higher brain functions and psychiatric illness.

PubMed

Zhao, Hua; Zhang, Bei-Lin; Yang, Shao-Jun; Rusak, Benjamin

2015-01-15

Serotonergic neurons in the dorsal raphe nucleus (DRN) play an important role in regulation of many physiological functions. The lateral nucleus of the habenular complex (LHb) is closely connected to the DRN both morphologically and functionally. The LHb is a key regulator of the activity of DRN serotonergic neurons, and it also receives reciprocal input from the DRN. The LHb is also a major way-station that receives limbic system input via the stria medullaris and provides output to the DRN and thereby indirectly connects a number of other brain regions to the DRN. The complex interactions of the LHb and DRN contribute to the regulation of numerous important behavioral and physiological mechanisms, including those regulating cognition, reward, pain sensitivity and patterns of sleep and waking. Disruption of these functions is characteristic of major psychiatric illnesses, so there has been a great deal of interest in how disturbed LHb-DRN interactions may contribute to the symptoms of these illnesses. This review summarizes recent research related to the roles of the LHb-DRN system in regulation of higher brain functions and the possible role of disturbed LHb-DRN function in the pathogenesis of psychiatric disorders, especially depression. Copyright © 2014 Elsevier B.V. All rights reserved.

Nutraceutical agents with anti-inflammatory properties prevent dietary saturated-fat induced disturbances in blood-brain barrier function in wild-type mice.

PubMed

Takechi, Ryusuke; Pallebage-Gamarallage, Menuka M; Lam, Virginie; Giles, Corey; Mamo, John C

2013-06-19

Emerging evidence suggests that disturbances in the blood-brain barrier (BBB) may be pivotal to the pathogenesis and pathology of vascular-based neurodegenerative disorders. Studies suggest that heightened systemic and central inflammations are associated with BBB dysfunction. This study investigated the effect of the anti-inflammatory nutraceuticals garlic extract-aged (GEA), alpha lipoic acid (ALA), niacin, and nicotinamide (NA) in a murine dietary-induced model of BBB dysfunction. C57BL/6 mice were fed a diet enriched in saturated fatty acids (SFA, 40% fat of total energy) for nine months to induce systemic inflammation and BBB disturbances. Nutraceutical treatment groups included the provision of either GEA, ALA, niacin or NA in the positive control SFA-group and in low-fat fed controls. Brain parenchymal extravasation of plasma derived immunoglobulin G (IgG) and large macromolecules (apolipoprotein (apo) B lipoproteins) measured by quantitative immunofluorescent microscopy, were used as markers of disturbed BBB integrity. Parenchymal glial fibrillar acidic protein (GFAP) and cyclooxygenase-2 (COX-2) were considered in the context of surrogate markers of neurovascular inflammation and oxidative stress. Total anti-oxidant status and glutathione reductase activity were determined in plasma. Brain parenchymal abundance of IgG and apoB lipoproteins was markedly exaggerated in mice maintained on the SFA diet concomitant with significantly increased GFAP and COX-2, and reduced systemic anti-oxidative status. The nutraceutical GEA, ALA, niacin, and NA completely prevented the SFA-induced disturbances of BBB and normalized the measures of neurovascular inflammation and oxidative stress. The anti-inflammatory nutraceutical agents GEA, ALA, niacin, or NA are potent inhibitors of dietary fat-induced disturbances of BBB induced by systemic inflammations.

[Brain concussion].

PubMed

Pälvimäki, Esa-Pekka; Siironen, Jari; Pohjola, Juha; Hernesniemi, Juha

2011-01-01

Brain concussion is a common disturbance caused by external forces or acceleration affecting the head. It may be accompanied by transient loss of consciousness and amnesia. Typical symptoms include headache, nausea and dizziness; these may remain for a week or two. Some patients may experience transient loss of inability to create new memories or other brief impairment of mental functioning. Treatment is symptomatic. Some patients may suffer from prolonged symptoms, the connection of which with brain concession is difficult to show. Almost invariably the prognosis of brain concussion is good.

Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson's Disease.

PubMed

Harrington, Deborah L; Shen, Qian; Castillo, Gabriel N; Filoteo, J Vincent; Litvan, Irene; Takahashi, Colleen; French, Chelsea

2017-01-01

Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI) are common in Parkinson's disease (PD), but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN) and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF) and regional homogeneity (ReHo), a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex), sensorimotor cortex (primary motor, pre/post-central gyrus), basal ganglia (putamen, caudate), and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a pathological, rather than compensatory influence on cognitive abilities tested in this study. Receiver operating curve analyses demonstrated excellent sensitivity (≥90%) of rsfMRI variables in distinguishing patients from controls, but poor accuracy for brain volume and cognitive variables. Altogether these results provide new insights into the topology, cognitive relevance, and sensitivity of aberrant intrinsic activity and connectivity that precedes clinically significant cognitive impairment. Longitudinal studies are needed to determine if these neurocognitive associations presage the development of future mild cognitive impairment or dementia.

Viewing the functional consequences of traumatic brain injury by using brain SPECT.

PubMed

Pavel, D; Jobe, T; Devore-Best, S; Davis, G; Epstein, P; Sinha, S; Kohn, R; Craita, I; Liu, P; Chang, Y

2006-03-01

High-resolution brain SPECT is increasingly benefiting from improved image processing software and multiple complementary display capabilities. This enables detailed functional mapping of the disturbances in relative perfusion occurring after TBI. The patient population consisted of 26 cases (ages 8-61 years)between 3 months and 6 years after traumatic brain injury.A very strong case can be made for the routine use of Brain SPECT in TBI. Indeed it can provide a detailed evaluation of multiple functional consequences after TBI and is thus capable of supplementing the clinical evaluation and tailoring the therapeutic strategies needed. In so doing it also provides significant additional information beyond that available from MRI/CT. The critical factor for Brain SPECT's clinical relevance is a carefully designed technical protocol, including displays which should enable a comprehensive description of the patterns found, in a user friendly mode.

Central neural mechanisms governing postural cardiovascular mechanisms

NASA Technical Reports Server (NTRS)

Reis, D. J.

1976-01-01

The results of the vestibular apparatus and cerebellum in orthostatic reflex control are summarized. Mechanisms within the brain which govern circulation reflexes and the consequences of disturbances in their function are also included.

Neuropsychological outcome after traumatic temporal lobe damage.

PubMed

Formisano, R; Schmidhuber-Eiler, B; Saltuari, L; Cigany, E; Birbamer, G; Gerstenbrand, F

1991-01-01

The most frequent sequelae after severe brain injury include changes in personality traits, disturbances of emotional behaviour and impairment of cognitive functions. In particular, emotional changes and/or verbal and non verbal dysfunctions were found in patients with bilateral or unilateral temporal lobe lesions. The aim of our study is to correlate the localization of the brain damage after severe brain injury, in particular of the temporal lobe, with the cognitive impairment and the emotional and behavioural changes resulting from these lesions. The patients with right temporal lobe lesions showed significantly better scores in verbal intelligence and verbal memory in comparison with patients with left temporal lobe lesions and those with other focal brain lesions or diffuse brain damage. In contradistinction, study of the personality and the emotional changes (MMPI and FAF) failed to demonstrate pathological scores in the 3 groups with different CT lesions, without any significant difference being found between the groups with temporal lesions and those with other focal brain lesions or diffuse brain damage. The severity of the brain injury and the prolongation of the disturbance of consciousness could, in our patients, account for prevalence of congnitive impairment on personality and emotional changes.

Sleep-wake disturbances in sporadic Creutzfeldt-Jakob disease.

PubMed

Landolt, H-P; Glatzel, M; Blättler, T; Achermann, P; Roth, C; Mathis, J; Weis, J; Tobler, I; Aguzzi, A; Bassetti, C L

2006-05-09

The prevalence and characteristics of sleep-wake disturbances in sporadic Creutzfeldt-Jakob disease (sCJD) are poorly understood. Seven consecutive patients with definite sCJD underwent a systematic assessment of sleep-wake disturbances, including clinical history, video-polysomnography, and actigraphy. Extent and distribution of neurodegeneration was estimated by brain autopsy in six patients. Western blot analyses enabling classification and quantification of the protease-resistant isoform of the prion protein, PrPSc, in thalamus and occipital cortex was available in four patients. Sleep-wake symptoms were observed in all patients, and were prominent in four of them. All patients had severe sleep EEG abnormalities with loss of sleep spindles, very low sleep efficiency, and virtual absence of REM sleep. The correlation between different methods to assess sleep-wake functions (history, polysomnography, actigraphy, videography) was generally poor. Brain autopsy revealed prominent changes in cortical areas, but only mild changes in the thalamus. No mutation of the PRNP gene was found. This study demonstrates in sporadic Creutzfeldt-Jakob disease, first, the existence of sleep-wake disturbances similar to those reported in fatal familial insomnia in the absence of prominent and isolated thalamic neuronal loss, and second, the need of a multimodal approach for the unambiguous assessment of sleep-wake functions in these patients.

Structural network efficiency is associated with cognitive impairment in small-vessel disease.

PubMed

Lawrence, Andrew J; Chung, Ai Wern; Morris, Robin G; Markus, Hugh S; Barrick, Thomas R

2014-07-22

To characterize brain network connectivity impairment in cerebral small-vessel disease (SVD) and its relationship with MRI disease markers and cognitive impairment. A cross-sectional design applied graph-based efficiency analysis to deterministic diffusion tensor tractography data from 115 patients with lacunar infarction and leukoaraiosis and 50 healthy individuals. Structural connectivity was estimated between 90 cortical and subcortical brain regions and efficiency measures of resulting graphs were analyzed. Networks were compared between SVD and control groups, and associations between efficiency measures, conventional MRI disease markers, and cognitive function were tested. Brain diffusion tensor tractography network connectivity was significantly reduced in SVD: networks were less dense, connection weights were lower, and measures of network efficiency were significantly disrupted. The degree of brain network disruption was associated with MRI measures of disease severity and cognitive function. In multiple regression models controlling for confounding variables, associations with cognition were stronger for network measures than other MRI measures including conventional diffusion tensor imaging measures. A total mediation effect was observed for the association between fractional anisotropy and mean diffusivity measures and executive function and processing speed. Brain network connectivity in SVD is disturbed, this disturbance is related to disease severity, and within a mediation framework fully or partly explains previously observed associations between MRI measures and SVD-related cognitive dysfunction. These cross-sectional results highlight the importance of network disruption in SVD and provide support for network measures as a disease marker in treatment studies. © 2014 American Academy of Neurology.

Structural network efficiency is associated with cognitive impairment in small-vessel disease

PubMed Central

Chung, Ai Wern; Morris, Robin G.; Markus, Hugh S.; Barrick, Thomas R.

2014-01-01

Objective: To characterize brain network connectivity impairment in cerebral small-vessel disease (SVD) and its relationship with MRI disease markers and cognitive impairment. Methods: A cross-sectional design applied graph-based efficiency analysis to deterministic diffusion tensor tractography data from 115 patients with lacunar infarction and leukoaraiosis and 50 healthy individuals. Structural connectivity was estimated between 90 cortical and subcortical brain regions and efficiency measures of resulting graphs were analyzed. Networks were compared between SVD and control groups, and associations between efficiency measures, conventional MRI disease markers, and cognitive function were tested. Results: Brain diffusion tensor tractography network connectivity was significantly reduced in SVD: networks were less dense, connection weights were lower, and measures of network efficiency were significantly disrupted. The degree of brain network disruption was associated with MRI measures of disease severity and cognitive function. In multiple regression models controlling for confounding variables, associations with cognition were stronger for network measures than other MRI measures including conventional diffusion tensor imaging measures. A total mediation effect was observed for the association between fractional anisotropy and mean diffusivity measures and executive function and processing speed. Conclusions: Brain network connectivity in SVD is disturbed, this disturbance is related to disease severity, and within a mediation framework fully or partly explains previously observed associations between MRI measures and SVD-related cognitive dysfunction. These cross-sectional results highlight the importance of network disruption in SVD and provide support for network measures as a disease marker in treatment studies. PMID:24951477

[Eating disorders].

PubMed

Miyake, Yoshie; Okamoto, Yuri; Jinnin, Ran; Shishida, Kazuhiro; Okamoto, Yasumasa

2015-02-01

Eating disorders are characterized by aberrant patterns of eating behavior, including such symptoms as extreme restriction of food intake or binge eating, and severe disturbances in the perception of body shape and weight, as well as a drive for thinness and obsessive fears of becoming fat. Eating disorder is an important cause for physical and psychosocial morbidity in young women. Patients with eating disorders have a deficit in the cognitive process and functional abnormalities in the brain system. Recently, brain-imaging techniques have been used to identify specific brain areas that function abnormally in patients with eating disorders. We have discussed the clinical and cognitive aspects of eating disorders and summarized neuroimaging studies of eating disorders.

Disrupted functional connectome in antisocial personality disorder.

PubMed

Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen; Wang, Wei; Shen, Dinggang

2017-08-01

Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD.

Disrupted functional connectome in antisocial personality disorder

PubMed Central

Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen

2017-01-01

Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD. PMID:27541949

Neuropsychiatric disorders in persons with severe traumatic brain injury: prevalence, phenomenology, and relationship with demographic, clinical, and functional features.

PubMed

Ciurli, Paola; Formisano, Rita; Bivona, Umberto; Cantagallo, Anna; Angelelli, Paola

2011-01-01

To characterize neuropsychiatric symptoms in a large group of individuals with severe traumatic brain injury (TBI) and to correlate these symptoms with demographic, clinical, and functional features. The Neuropsychiatric Inventory (NPI), a frequently used scale to assess behavioral, emotional, and motivational disorders in persons with neurological diseases, was administered to a sample of 120 persons with severe TBI. Controls were 77 healthy subjects. A wide range of neuropsychiatric symptoms was found in the population with severe TBI: apathy (42%), irritability (37%), dysphoria/depressed mood (29%), disinhibition (28%), eating disturbances (27%), and agitation (24%). A clear relationship was also found with other demographic and clinical variables. Neuropsychiatric disorders constitute an important part of the comorbidity in populations with severe TBI. Our study emphasizes the importance of integrating an overall assessment of cognitive disturbances with a specific neuropsychiatric evaluation to improve clinical understanding and treatment of persons with TBI.

Effects of geomagnetic activity variations on the physiological and psychological state of functionally healthy humans: Some results of Azerbaijani studies

NASA Astrophysics Data System (ADS)

Babayev, Elchin S.; Allahverdiyeva, Aysel A.

There are collaborative and cross-disciplinary space weather studies in the Azerbaijan National Academy of Sciences conducted with purposes of revealing possible effects of solar, geomagnetic and cosmic ray variability on certain technological, biological and ecological systems. This paper describes some results of the experimental studies of influence of the periodical and aperiodical changes of geomagnetic activity upon human brain, human health and psycho-emotional state. It also covers the conclusions of studies on influence of violent solar events and severe geomagnetic storms of the solar cycle 23 on the mentioned systems in middle-latitude location. It is experimentally established that weak and moderate geomagnetic storms do not cause significant changes in the brain's bioelectrical activity and exert only stimulating influence while severe disturbances of geomagnetic conditions cause negative influence, seriously disintegrate brain's functionality, activate braking processes and amplify the negative emotional background of an individual. It is concluded that geomagnetic disturbances affect mainly emotional and vegetative spheres of human beings while characteristics reflecting personality properties do not undergo significant changes.

PET imaging in ischemic cerebrovascular disease: current status and future directions.

PubMed

Heiss, Wolf-Dieter

2014-10-01

Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the flow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies. Radioligands for receptors can be used as early markers of irreversible neuronal damage and thereby can predict the size of the final infarcts; this is also important for decisions concerning invasive therapy in large ("malignant") infarctions. With PET investigations, the reserve capacity of blood supply to the brain can be tested in obstructive arteriosclerosis of the supplying arteries, and this again is essential for planning interventions. The effect of a stroke on the surrounding and contralateral primarily unaffected tissue can be investigated, and these results help to understand the symptoms caused by disturbances in functional networks. Chronic cerebrovascular disease causes vascular cognitive disorders, including vascular dementia. PET permits the detection of the metabolic disturbances responsible for cognitive impairment and dementia, and can differentiate vascular dementia from degenerative diseases. It may also help to understand the importance of neuroinflammation after stroke and its interaction with amyloid deposition in the development of dementia. Although the clinical application of PET investigations is limited, this technology had and still has a great impact on research into cerebrovascular diseases.

Neural correlates of reward-based spatial learning in persons with cocaine dependence.

PubMed

Tau, Gregory Z; Marsh, Rachel; Wang, Zhishun; Torres-Sanchez, Tania; Graniello, Barbara; Hao, Xuejun; Xu, Dongrong; Packard, Mark G; Duan, Yunsuo; Kangarlu, Alayar; Martinez, Diana; Peterson, Bradley S

2014-02-01

Dysfunctional learning systems are thought to be central to the pathogenesis of and impair recovery from addictions. The functioning of the brain circuits for episodic memory or learning that support goal-directed behavior has not been studied previously in persons with cocaine dependence (CD). Thirteen abstinent CD and 13 healthy participants underwent MRI scanning while performing a task that requires the use of spatial cues to navigate a virtual-reality environment and find monetary rewards, allowing the functional assessment of the brain systems for spatial learning, a form of episodic memory. Whereas both groups performed similarly on the reward-based spatial learning task, we identified disturbances in brain regions involved in learning and reward in CD participants. In particular, CD was associated with impaired functioning of medial temporal lobe (MTL), a brain region that is crucial for spatial learning (and episodic memory) with concomitant recruitment of striatum (which normally participates in stimulus-response, or habit, learning), and prefrontal cortex. CD was also associated with enhanced sensitivity of the ventral striatum to unexpected rewards but not to expected rewards earned during spatial learning. We provide evidence that spatial learning in CD is characterized by disturbances in functioning of an MTL-based system for episodic memory and a striatum-based system for stimulus-response learning and reward. We have found additional abnormalities in distributed cortical regions. Consistent with findings from animal studies, we provide the first evidence in humans describing the disruptive effects of cocaine on the coordinated functioning of multiple neural systems for learning and memory.

[Effects of diabetes and obesity on the higher brain functions in rodents].

PubMed

Asato, Megumi; Ikeda, Hiroko; Kamei, Junzo

2012-11-01

Metabolic disorders, such as diabetes and obesity, have been indicated to disturb the function of the central nervous system (CNS) as well as several peripheral organs. Clinically, it is well recognized that the prevalence of anxiety and depression is higher in diabetic and obesity patients than in the general population. We have recently indicated that streptozotocin-induced diabetic and diet-induced obesity mice have enhanced fear memory and higher anxiety-like behavior in several tests such as the conditioned fear, tail-suspension, hole-board and elevated open-platform tests. The changes in fear memory and anxiety-like behavior of diabetic and obese mice are due to the dysfunction of central glutamatergic and monoaminergic systems, which is mediated by the changes of intracellular signaling. These results suggest that metabolic disorders strongly affect the function of the CNS and disturb the higher brain functions. These dysfunctions of the CNS in diabetes and obesity are involved in the increased prevalence of anxiety disorders and depression. Normalization of these dysfunctions in the CNS will be a new attractive target to treat the metabolic disorders and their complications.

Sleep disturbance induces neuroinflammation and impairment of learning and memory.

PubMed

Zhu, Biao; Dong, Yuanlin; Xu, Zhipeng; Gompf, Heinrich S; Ward, Sarah A P; Xue, Zhanggang; Miao, Changhong; Zhang, Yiying; Chamberlin, Nancy L; Xie, Zhongcong

2012-12-01

Hospitalized patients can develop cognitive function decline, the mechanisms of which remain largely to be determined. Sleep disturbance often occurs in hospitalized patients, and neuroinflammation can induce learning and memory impairment. We therefore set out to determine whether sleep disturbance can induce neuroinflammation and impairment of learning and memory in rodents. Five to 6-month-old wild-type C57BL/6J male mice were used in the studies. The mice were placed in rocking cages for 24 h, and two rolling balls were present in each cage. The mice were tested for learning and memory function using the Fear Conditioning Test one and 7 days post-sleep disturbance. Neuroinflammation in the mouse brain tissues was also determined. Of the Fear Conditioning studies at one day and 7 days after sleep disturbance, twenty-four hour sleep disturbance decreased freezing time in the context test, which assesses hippocampus-dependent learning and memory; but not the tone test, which assesses hippocampus-independent learning and memory. Sleep disturbance increased pro-inflammatory cytokine IL-6 levels and induced microglia activation in the mouse hippocampus, but not the cortex. These results suggest that sleep disturbance induces neuroinflammation in the mouse hippocampus, and impairs hippocampus-dependent learning and memory in mice. Pending further studies, these findings suggest that sleep disturbance-induced neuroinflammation and impairment of learning and memory may contribute to the development of cognitive function decline in hospitalized patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Direct observation of cerebrospinal fluid bulk flow in the brain

NASA Astrophysics Data System (ADS)

Mestre, Humberto; Tithof, Jeffrey; Thomas, John; Kelley, Douglas; Nedergaard, Maiken

2017-11-01

Cerebrospinal fluid (CSF) serves a vital role in normal brain function. Its adequate flow and exchange with interstitial fluid through perivascular spaces (PVS) has been shown to be important in the clearance of toxic metabolites like amyloid- β, and its disturbance can cause severe neurological diseases. It has long been suspected that bulk flow may transport CSF, but limitations in imaging techniques have prevented direct observation of such flows in the PVS. In this talk, we describe a novel approach using high speed two photon laser scanning microscopy which has allowed for the first ever direct observation of CSF flow in the PVS of a mouse brain. By performing particle tracking velocimetry, we quantify the CSF bulk flow speeds and PVS geometry. This technique enables future studies of CSF flow disturbances on a new scale and will pave the way for evaluating the role of these fluxes in neurodegenerative disease. R01NS100366 (to M.N.).

[Disorders of endocrine function after brain tumor therapy in childhood].

PubMed

Marx, M; Langer, T; Beck, J D; Dörr, H G

1999-07-01

Advances in the therapy of malignant brain tumors in children have led to a significant improvement in survival rates over the last few decades. As a result, the recognition and treatment of late effects have become more important. In addition to secondary tumors and deficiencies in cognitive and intellectual skills, the resulting endocrine disturbances play an important role. Own data and literature review. Deviations from the normal growth hormone secretion are usually recognized first and are most common, and have already been observed after conventional whole brain irradiation with 18 Gy. With some delay, other hypothalamo-pituitary deficiencies may occur, including panhypopituitarism. Puberty may come too early or too late or may not appear at all. Girls in particular, frequently experience an early and rapid pubertal development after brain tumor therapy, which may lead to further reduction in height due to an accelerated bone maturation. Functional disturbances of the thyroid and adrenal glands due to hypothalamic or pituitary deficiency are less common, and usually seen only after a radiation dose of over 40 Gy. Survivors of childhood brain tumors must be considered as long-term survivors, in whom the first therapy-induced long-term side effects appear almost immediately after the end of therapy. Maximum quality of life for the individual patient can only be achieved by long-term care and close cooperation of specialists in the different medical disciplines involved.

Effects of diabetes on brain metabolism--is brain glycogen a significant player?

PubMed

Sickmann, Helle M; Waagepetersen, Helle S

2015-02-01

Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose to the brain may be affected and have important impacts on brain metabolism and neurotransmission. This also implies that brain glycogen may serve an essential role in the diabetic state to sustain appropriate brain function. There are two main types of diabetes; type 1 and type 2 diabetes and both types may be associated with brain impairments e.g. cognitive decline and dementia. It is however, not clear how these impairments on brain function are linked to alterations in brain energy and neurotransmitter metabolism. In this review, we will illuminate how rodent diabetes models have contributed to a better understanding of how brain energy and neurotransmitter metabolism is affected in diabetes. There will be a particular focus on the role of brain glycogen to support glycolytic and TCA cycle activity as well as glutamate-glutamine cycle in type 1 and type 2 diabetes.

Devices for noninvasive transcranial electrostimulation of the brain endorphinergic system: application for improvement of human psycho-physiological status.

PubMed

Lebedev, Valery P; Malygin, A V; Kovalevski, A V; Rychkova, S V; Sisoev, V N; Kropotov, S P; Krupitski, E M; Gerasimova, L I; Glukhov, D V; Kozlowski, G P

2002-03-01

It is well known that deficit of endorphins plays an important role in disturbances of human psycho-physiological status. Previously, we revealed that brain endorphinergic structures have quasiresonance characteristics. On the basis of these data, a method of activation of the brain endorphinergic structures by means of noninvasive and rather selective transcranial electrostimulation (TES) as a kind of functional electrical stimulation (FES) was elaborated. New models of TES devices (TRANSAIR) were developed for indoor and outdoor usage. To increase the efficacy of TES, the frequency modulation according to normal distribution in the limits of the quasiresonance characteristics was put into operation. The blind and placebo-controlled (passive and active placebo) study was produced to estimate the TES effects on stress events and accompanied psycho-physiological and autonomic disturbances of different intensities on volunteers and patients in the following groups: everyday stress and fatigue; stress in regular military service and in field conditions; stress in the relatives of those lost in mass disaster; posttraumatic stress (thermal burns); and affective disorders in a postabstinence period. Some subjective verbal and nonverbal tests and objective tests (including heart rate variability) were used for estimation of the initial level of psycho-physiological status, which changes after TES sessions. It was demonstrated that fatigue, stress, and other accompanied psycho-physiological disturbances were significantly improved or abolished after 2-5 TES sessions. The TES effects were more pronounced in cases of heavier disturbances. In conclusion, activation of the brain endorphinergic structures by TES is an effective homeostatic method of FES that sufficiently improves quality of life.

Autism as an adaptive common variant pathway for human brain development.

PubMed

Johnson, Mark H

2017-06-01

While research on focal perinatal lesions has provided evidence for recovery of function, much less is known about processes of brain adaptation resulting from mild but widespread disturbances to neural processing over the early years (such as alterations in synaptic efficiency). Rather than being viewed as a direct behavioral consequence of life-long neural dysfunction, I propose that autism is best viewed as the end result of engaging adaptive processes during a sensitive period. From this perspective, autism is not appropriately described as a disorder of neurodevelopment, but rather as an adaptive common variant pathway of human functional brain development. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

The stomach-brain axis.

PubMed

Holtmann, Gerald; Talley, Nicholas J

2014-12-01

The stomach has distinct functions in relation to the ingestion and handling of solids and liquids. These functions include storage of the food before it is gradually emptied into the duodenum, mechanical crushing of larger food particles to increase the surface area, secretion of an acidic enzyme rich gastric juice and mixing the ingested food with the gastric juice. In addition, the stomach 'senses' the composition of the gastric content and this information is passed via the vagal nerve to the lateral hypothalamus and the limbic system, most likely as palatability signals that influence eating behaviour. Other sensory qualities related to the stimulation of gastric tension receptors are satiety and fullness. Receptors that respond to macronutrient content or gastric wall tension influence appetite and meal related hormone responses. The ingestion of food - in contrast to an infusion of nutrients into the stomach - has distinct effects on the activation of specific brain regions. Brain areas such as thalamus, amygdala, putamen and praecuneus are activated by the ingestion of food. Gastric nutrient infusion evokes greater activation in the hippocampus and anterior cingulate. The brain integrates these interrelated neural and hormonal signals arising from the stomach as well as visual, olfactory and anticipatory stimuli that ultimately influence eating and other behavioural patterns. Furthermore, there is now good evidence from experimental studies that gastric afferents influence mood, and animal studies point towards the possibility that gastric dysfunction may be a risk factor for mood disorders such as anxiety and depression. The stomach is also not only colonised by Helicobacter pylori but a large array of bacteria. While there is sufficient evidence to suggest that H. pylori may alter caloric intake and mood, the role of other gastric microbiome for the brain function is unknown. To address this appropriate targeted gastric microbiome studies would be required instead of widely utilised opportunistic stool microbiome studies. In summary, it is now well established that there are important links between the brain and the stomach that have significant effects on gastric function. However, the stomach also influences the brain. Disturbances in the crosstalk between the stomach and the brain may manifest as functional GI disorders while disturbances in the stomach-brain communication may also result in an altered regulation of satiety and as a consequence may affect eating behaviour and mood. These observations may enable the identification of novel therapies targeted at the gastroduodenum that positively alter brain function and treat or prevent conditions such as obesity or functional gastrointestinal disorders. Copyright © 2014. Published by Elsevier Ltd.

Macrophages and depression - a misalliance or well-arranged marriage?

PubMed

Roman, Adam; Kreiner, Grzegorz; Nalepa, Irena

2013-01-01

Depression is a severe medical condition with multiple manifestations and diverse, largely unknown etiologies. The immune system, particularly macrophages, plays an important role in the pathology of the illness. Macrophages represent a heterogeneous population of immune cells that is dispersed throughout the body. The central nervous system is populated by several types of macrophages, including microglia, perivascular cells, meningeal and choroid plexus macrophages and pericytes. These cells occupy different brain compartments and have various functions. Under basal conditions, brain macrophages support the proper function of neural cells, organize and preserve the neuronal network and maintain homeostasis. As cells of the innate immune system, they recognize and react to any disturbances in homeostasis, eliminating pathogens or damaged cells, terminating inflammation and proceeding to initiate tissue reconstruction. Disturbances in these processes result in diverse pathologies. In particular, tissue stress or malfunction, both in the brain and in the periphery, produce sustained inflammatory states, which may cause depression. Excessive release of proinflammatory mediators is responsible for alterations of neurotransmitter systems and the occurrence of depressive symptoms. Almost all antidepressive drugs target monoamine or serotonin neurotransmission and also have anti-inflammatory or immunosuppressive properties. In addition, non-pharmacological treatments, such as electroconvulsive shock, can also exert anti-inflammatory effects. Recent studies have shown that antidepressive therapies can affect the functional properties of peripheral and brain macrophages and skew them toward the anti-inflammatory M2 phenotype. Because macrophages can affect outcome of inflammatory diseases, alleviate sickness behavior and improve cognitive function, it is possible that the effects of antidepressive treatments may be, at least in part, mediated by changes in macrophage activity.

Relationship between regional cerebral metabolism and consciousness disturbance in traumatic diffuse brain injury without large focal lesions: an FDG-PET study with statistical parametric mapping analysis.

PubMed

Nakayama, N; Okumura, A; Shinoda, J; Nakashima, T; Iwama, T

2006-07-01

The cerebral metabolism of patients in the chronic stage of traumatic diffuse brain injury (TDBI) has not been fully investigated. To study the relationship between regional cerebral metabolism (rCM) and consciousness disturbance in patients with TDBI. 52 patients with TDBI in the chronic stage without large focal lesions were enrolled, and rCM was evaluated by fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) with statistical parametric mapping (SPM). All the patients were found to have disturbed consciousness or cognitive function and were divided into the following three groups: group A (n = 22), patients in a state with higher brain dysfunction; group B (n = 13), patients in a minimally conscious state; and group C (n = 17), patients in a vegetative state. rCM patterns on FDG-PET among these groups were evaluated and compared with those of normal control subjects on statistical parametric maps. Hypometabolism was consistently indicated bilaterally in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus. Hypometabolism in these regions was the most widespread and prominent in group C, and that in group B was more widespread and prominent than that in group A. Bilateral hypometabolism in the medial prefrontal regions, the medial frontobasal regions, the cingulate gyrus and the thalamus may reflect the clinical deterioration of TDBI, which is due to functional and structural disconnections of neural networks rather than due to direct cerebral focal contusion.

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions.

PubMed

Zhang, Dong-Mei; Jiao, Rui-Qing; Kong, Ling-Dong

2017-03-29

High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption.

High Dietary Fructose: Direct or Indirect Dangerous Factors Disturbing Tissue and Organ Functions

PubMed Central

Zhang, Dong-Mei; Jiao, Rui-Qing; Kong, Ling-Dong

2017-01-01

High dietary fructose is a major contributor to insulin resistance and metabolic syndrome, disturbing tissue and organ functions. Fructose is mainly absorbed into systemic circulation by glucose transporter 2 (GLUT2) and GLUT5, and metabolized in liver to produce glucose, lactate, triglyceride (TG), free fatty acid (FFA), uric acid (UA) and methylglyoxal (MG). Its extrahepatic absorption and metabolism also take place. High levels of these metabolites are the direct dangerous factors. During fructose metabolism, ATP depletion occurs and induces oxidative stress and inflammatory response, disturbing functions of local tissues and organs to overproduce inflammatory cytokine, adiponectin, leptin and endotoxin, which act as indirect dangerous factors. Fructose and its metabolites directly and/or indirectly cause oxidative stress, chronic inflammation, endothelial dysfunction, autophagy and increased intestinal permeability, and then further aggravate the metabolic syndrome with tissue and organ dysfunctions. Therefore, this review addresses fructose-induced metabolic syndrome, and the disturbance effects of direct and/or indirect dangerous factors on the functions of liver, adipose, pancreas islet, skeletal muscle, kidney, heart, brain and small intestine. It is important to find the potential correlations between direct and/or indirect risk factors and healthy problems under excess dietary fructose consumption. PMID:28353649

Microglia, the missing link in maternal immune activation and fetal neurodevelopment; and a possible link in preeclampsia and disturbed neurodevelopment?

PubMed

Prins, Jelmer R; Eskandar, Sharon; Eggen, Bart J L; Scherjon, Sicco A

2018-04-01

Disturbances in fetal neurodevelopment have extensively been related to neurodevelopmental disorders in early and later life. Fetal neurodevelopment is dependent on adequate functioning of the fetal immune system. During pregnancy, the maternal immune system is challenged to both tolerate the semi-allogenic fetus and to protect the mother and fetus from microbes. The fetal immune system is influenced by maternal immune disturbances; therefore, perturbations in maternal immunity likely do not only alter pregnancy outcome but also alter fetal neurodevelopment. A possible common pathway could be modulating the functioning of tissue macrophages in the placenta and brain. Maternal immune tolerance towards the fetus involves several complex adaptations. In this active maternal immune state, the fetus develops its own immunity. As cytokines and other players of the immune system -which can pass the placenta- are involved in neurodevelopment, disruptions in immune balance influence fetal neurodevelopment. Several studies reported an association between maternal immune activation, complications of pregnancy as preeclampsia, and altered neonatal neurodevelopment. A possible pathway involves dysfunctioning of microglia cells, the immune cells of the brain. Functionality of microglia cells during normal pregnancy is, however, poorly understood. The recent outbreak of ZIKA virus (ZKV), but also the literature on virus infections in general and its consequences on microglial cell function and fetal neurodevelopment show the devastating effects a virus infection during pregnancy can have. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Sleep, sleep disorders, and circadian health following mild traumatic brain injury: Review and research agenda.

PubMed

Wickwire, Emerson; Schnyer, David M; Germain, Anne; Williams, Scott; Lettieri, Christopher; McKeon, Ashlee; Scharf, Steven; Stocker, Ryan; Albrecht, Jennifer S; Badjatia, Neeraj; Markowitz, Amy; Manley, Geoffrey

2018-06-07

A rapidly expanding scientific literature supports the frequent co-occurrence of sleep and circadian disturbances following mild traumatic brain injury (mTBI). Although many questions remain unanswered, the preponderance of evidence suggests that sleep and circadian disorders can result from mTBI. Among those with mTBI, sleep disturbances and clinical sleep and circadian disorders contribute to the morbidity and long-term sequelae across domains of functional outcomes and quality of life. Specifically, along with deterioration of neurocognitive performance, insufficient and disturbed sleep can precede, exacerbate, or perpetuate many of the other common sequelae of mTBI, including depression, post-traumatic stress disorder, and chronic pain. Further, sleep and mTBI share neurophysiologic and neuroanatomic mechanisms that likely bear directly on success of rehabilitation following mTBI. For these reasons, focus on disturbed sleep as a modifiable treatment target has high likelihood of improving outcomes in mTBI. Here, we review relevant literature and present a research agenda to 1) advance understanding of the reciprocal relationships between sleep and circadian factors and mTBI sequelae and 2) advance rapidly the development of sleep-related treatments in this population.

Systematic analysis of microarray datasets to identify Parkinson's disease‑associated pathways and genes.

PubMed

Feng, Yinling; Wang, Xuefeng

2017-03-01

In order to investigate commonly disturbed genes and pathways in various brain regions of patients with Parkinson's disease (PD), microarray datasets from previous studies were collected and systematically analyzed. Different normalization methods were applied to microarray datasets from different platforms. A strategy combining gene co‑expression networks and clinical information was adopted, using weighted gene co‑expression network analysis (WGCNA) to screen for commonly disturbed genes in different brain regions of patients with PD. Functional enrichment analysis of commonly disturbed genes was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Co‑pathway relationships were identified with Pearson's correlation coefficient tests and a hypergeometric distribution‑based test. Common genes in pathway pairs were selected out and regarded as risk genes. A total of 17 microarray datasets from 7 platforms were retained for further analysis. Five gene coexpression modules were identified, containing 9,745, 736, 233, 101 and 93 genes, respectively. One module was significantly correlated with PD samples and thus the 736 genes it contained were considered to be candidate PD‑associated genes. Functional enrichment analysis demonstrated that these genes were implicated in oxidative phosphorylation and PD. A total of 44 pathway pairs and 52 risk genes were revealed, and a risk gene pathway relationship network was constructed. Eight modules were identified and were revealed to be associated with PD, cancers and metabolism. A number of disturbed pathways and risk genes were unveiled in PD, and these findings may help advance understanding of PD pathogenesis.

Altered Brain Long-Range Functional Interactions Underlying the Link Between Aberrant Self-experience and Self-other Relationship in First-Episode Schizophrenia

PubMed Central

Ebisch, Sjoerd J. H.; Mantini, Dante; Northoff, Georg; Salone, Anatolia; De Berardis, Domenico; Ferri, Francesca; Ferro, Filippo M.; Di Giannantonio, Massimo; Romani, Gian L.; Gallese, Vittorio

2014-01-01

Self-experience anomalies are elementary features of schizophrenic pathology. Such deficits can have a profound impact on self-other relationship, but how they are related through aberrant brain function remains poorly understood. In this functional magnetic resonance imaging (fMRI) study, we provide new evidence for a cortical link between aberrant self-experience and social cognition in first-episode schizophrenia (FES). As identified in previous studies, ventral premotor cortex (vPMC) and posterior insula (pIC) are candidate brain regions underlying disturbances in both self-experience and self-other relationship due to their processing of predominantly externally guided (vPMC; goal-oriented behavior) and internally guided (pIC; interoception) stimuli. Results from functional interaction analysis in a sample of 24 FES patients and 22 healthy controls show aberrant functional interactions (background/intrinsic connectivity) of right vPMC and bilateral pIC with posterior cingulate cortex (PCC), a midline region that has been shown central in mediating self-experience. More specifically, our results show increased functional coupling between vPMC and PCC, which positively correlated with basic symptoms (subjective self-experience disturbances). pIC showed reduced functional coupling with PCC and postcentral gyrus and increased functional interactions with anterior insula. Taken together, our results suggest an imbalance in the processing between internally and externally guided information and its abnormal integration with self-referential processing as mediated by PCC. Due to our correlation findings, we suggest this imbalance to be closely related to basic symptoms in FES and thus anomalous self-experience. The findings further disentangle the cortical basis of how self-experience anomalies may pervade the social domain. PMID:24191160

The Interface between Neuroscience and Neuro-Psychoanalysis: Focus on Brain Connectivity

PubMed Central

Salone, Anatolia; Di Giacinto, Alessandra; Lai, Carlo; De Berardis, Domenico; Iasevoli, Felice; Fornaro, Michele; De Risio, Luisa; Santacroce, Rita; Martinotti, Giovanni; Giannantonio, Massimo Di

2016-01-01

Over the past 20 years, the advent of advanced techniques has significantly enhanced our knowledge on the brain. Yet, our understanding of the physiological and pathological functioning of the mind is still far from being exhaustive. Both the localizationist and the reductionist neuroscientific approaches to psychiatric disorders have proven to be largely unsatisfactory and are outdated. Accruing evidence suggests that psychoanalysis can engage the neurosciences in a productive and mutually enriching dialogue that may further our understanding of psychiatric disorders. In particular, advances in brain connectivity research have provided evidence supporting the convergence of neuroscientific findings and psychoanalysis and helped characterize the circuitry and mechanisms that underlie higher brain functions. In the present paper we discuss how knowledge on brain connectivity can impact neuropsychoanalysis, with a particular focus on schizophrenia. Brain connectivity studies in schizophrenic patients indicate complex alterations in brain functioning and circuitry, with particular emphasis on the role of cortical midline structures (CMS) and the default mode network (DMN). These networks seem to represent neural correlates of psychodynamic concepts central to the understanding of schizophrenia and of core psychopathological alterations of this disorder (i.e., ego disturbances and impaired primary process thinking). PMID:26869904

The character of sleep disturbances produced by multiple administrations of atropine the antagonist of brain muscarinic cholinergic system.

PubMed

Maglakelidze, N T; Chkhartishvili, E V; Mchedlidze, O M; Dzadzamiia, Sh Sh; Nachkebiia, N G

2012-03-01

Modification of brain muscarinic cholinergic system normal functioning can be considered as an appropriate strategy for the study of its role in sleep-wakefulness cycle basic mechanisms in general and in the course/maintenance of PS in particular. For this aim systemic application of muscarinic cholinoreceptors antagonists is significant because it gives possibility to modify functioning all of known five sub-types of muscarinic cholinoreceptors and to study the character of sleep disturbances in these conditions. Problem is very topical because the question about the intimate aspects of BMChS involvement in PS maintaining mechanisms still remains unsolved. In cats Atropine systemic administration was made once daily at 10:00 a.m. and continuous EEG registration of sleep-wakefulness cycle ultradian structure, lasting for 10 hour daily, was started immediately. In sum each animal received anti-muscarinic drugs for 12 times. Thereafter drug administrations were ceased and EEG registration of sleep-wakefulness cycle ultradian structure was continued during 10 consecutive days. On the basis of results obtained in these conditions we can conclude that brain muscarinic cholinergic system normal functioning is significant for basic mechanisms of sleep-wakefulness cycle. During wakefulness, at the level of neocortex and hippocampus, MChS supports only EEG activation, while it is one of the main factors in PS triggering and maintaining mechanisms.

Whole-brain analytic measures of network communication reveal increased structure-function correlation in right temporal lobe epilepsy.

PubMed

Wirsich, Jonathan; Perry, Alistair; Ridley, Ben; Proix, Timothée; Golos, Mathieu; Bénar, Christian; Ranjeva, Jean-Philippe; Bartolomei, Fabrice; Breakspear, Michael; Jirsa, Viktor; Guye, Maxime

2016-01-01

The in vivo structure-function relationship is key to understanding brain network reorganization due to pathologies. This relationship is likely to be particularly complex in brain network diseases such as temporal lobe epilepsy, in which disturbed large-scale systems are involved in both transient electrical events and long-lasting functional and structural impairments. Herein, we estimated this relationship by analyzing the correlation between structural connectivity and functional connectivity in terms of analytical network communication parameters. As such, we targeted the gradual topological structure-function reorganization caused by the pathology not only at the whole brain scale but also both in core and peripheral regions of the brain. We acquired diffusion (dMRI) and resting-state fMRI (rsfMRI) data in seven right-lateralized TLE (rTLE) patients and fourteen healthy controls and analyzed the structure-function relationship by using analytical network communication metrics derived from the structural connectome. In rTLE patients, we found a widespread hypercorrelated functional network. Network communication analysis revealed greater unspecific branching of the shortest path (search information) in the structural connectome and a higher global correlation between the structural and functional connectivity for the patient group. We also found evidence for a preserved structural rich-club in the patient group. In sum, global augmentation of structure-function correlation might be linked to a smaller functional repertoire in rTLE patients, while sparing the central core of the brain which may represent a pathway that facilitates the spread of seizures.

Increased Sleep Need and Reduction of Tuberomammillary Histamine Neurons after Rodent Traumatic Brain Injury.

PubMed

Noain, Daniela; Büchele, Fabian; Schreglmann, Sebastian R; Valko, Philipp O; Gavrilov, Yuri V; Morawska, Marta M; Imbach, Lukas L; Baumann, Christian R

2018-01-01

Although sleep-wake disturbances are prevalent and well described after traumatic brain injury, their pathophysiology remains unclear, most likely because human traumatic brain injury is a highly heterogeneous entity that makes the systematic study of sleep-wake disturbances in relation to trauma-induced histological changes a challenging task. Despite increasing interest, specific and effective treatment strategies for post-traumatic sleep-wake disturbances are still missing. With the present work, therefore, we aimed at studying acute and chronic sleep-wake disturbances by electrophysiological means, and at assessing their histological correlates after closed diffuse traumatic brain injury in rats with the ultimate goal of generating a model of post-traumatic sleep-wake disturbances and associated histopathological findings that accurately represents the human condition. We assessed sleep-wake behavior by means of standard electrophysiological recordings before and 1, 7, and 28 days after sham or traumatic brain injury procedures. Sleep-wake findings were then correlated to immunohistochemically labeled and stereologically quantified neuronal arousal systems. Compared with control animals, we found that closed diffuse traumatic brain injury caused increased sleep need one month after trauma, and sleep was more consolidated. As histological correlate, we found a reduced number of histamine immunoreactive cells in the tuberomammillary nucleus, potentially related to increased neuroinflammation. Monoaminergic and hypocretinergic neurotransmitter systems in the hypothalamus and rostral brainstem were not affected, however. These results suggest that our rat traumatic brain injury model reflects human post-traumatic sleep-wake disturbances and associated histopathological findings very accurately, thus providing a study platform for novel treatment strategies for affected patients.

PET scan perfusion imaging in the Prader–Willi syndrome: new insights into the psychiatric and social disturbances

PubMed Central

Mantoulan, Carine; Payoux, Pierre; Diene, Gwenaëlle; Glattard, Mélanie; Rogé, Bernadette; Molinas, Catherine; Sevely, Annick; Zilbovicius, Monica; Celsis, Pierre; Tauber, Maïthé

2011-01-01

The Prader–Willi syndrome (PWS), a rare multisystem genetic disease, leads to severe disabilities, such as morbid obesity, endocrine dysfunctions, psychiatric disorders, and social disturbances. We explored the whole brain of patients with PWS to detect abnormalities that might explain the behavioral and social disturbances, as well as the psychiatric disorders of these patients. Nine patients with PWS (six males, three females; mean age 16.4 years) underwent a positron emission tomography (PET) scan with H215O as a tracer to measure regional cerebral blood flow (rCBF). The images were compared with those acquired from nine controls (six males, three females; mean age 21.2 years). A morphologic magnetic resonance imaging (MRI) was also performed in PWS patients, and their cognitive and behavioral skills were assessed with Wechsler Intelligence Scale for Children III and the Child Behavior Check List (CBCL). The MRI images showed no evident anatomic abnormalities, whereas PET scans revealed hypoperfused brain regions in PWS patients compared with controls, particularly in the anterior cingulum and superior temporal regions. We observed a significant relationship (P<0.05) between rCBF in the hypoperfused regions and CBCL scores. The functional consequences of these perfusion abnormalities in specific brain regions might explain the behavioral and social problems observed in these individuals. PMID:20588317

PET scan perfusion imaging in the Prader-Willi syndrome: new insights into the psychiatric and social disturbances.

PubMed

Mantoulan, Carine; Payoux, Pierre; Diene, Gwenaëlle; Glattard, Mélanie; Rogé, Bernadette; Molinas, Catherine; Sevely, Annick; Zilbovicius, Monica; Celsis, Pierre; Tauber, Maïthé

2011-01-01

The Prader-Willi syndrome (PWS), a rare multisystem genetic disease, leads to severe disabilities, such as morbid obesity, endocrine dysfunctions, psychiatric disorders, and social disturbances. We explored the whole brain of patients with PWS to detect abnormalities that might explain the behavioral and social disturbances, as well as the psychiatric disorders of these patients. Nine patients with PWS (six males, three females; mean age 16.4 years) underwent a positron emission tomography (PET) scan with H(2)(15)O as a tracer to measure regional cerebral blood flow (rCBF). The images were compared with those acquired from nine controls (six males, three females; mean age 21.2 years). A morphologic magnetic resonance imaging (MRI) was also performed in PWS patients, and their cognitive and behavioral skills were assessed with Wechsler Intelligence Scale for Children III and the Child Behavior Check List (CBCL). The MRI images showed no evident anatomic abnormalities, whereas PET scans revealed hypoperfused brain regions in PWS patients compared with controls, particularly in the anterior cingulum and superior temporal regions. We observed a significant relationship (P<0.05) between rCBF in the hypoperfused regions and CBCL scores. The functional consequences of these perfusion abnormalities in specific brain regions might explain the behavioral and social problems observed in these individuals.

QEEG characteristics and spectrum weighted frequency for children diagnosed as autistic spectrum disorder.

PubMed

Pop-Jordanova, Nada; Zorcec, Tatjana; Demerdzieva, Aneta; Gucev, Zoran

2010-09-30

Autistic spectrum disorders are a group of neurological and developmental disorders associated with social, communication, sensory, behavioral and cognitive impairments, as well as restricted, repetitive patterns of behavior, activities, or interests.The aim of this study was a) to analyze QEEG findings of autistic patients and to compare the results with data base; and b) to introduce the calculation of spectrum weighted frequency (brain rate) as an indicator of general mental arousal in these patients. Results for Q-EEG shows generally increased delta-theta activity in frontal region of the brain. Changes in QEEG pattern appeared to be in a non-linear correlation with maturational processes.Brain rate measured in CZ shows slow brain activity (5. 86) which is significantly lower than normal and corresponds to low general mental arousal.Recent research has shown that autistic disorders have as their basis disturbances of neural connectivity. Neurofeedback seems capable of remediating such disturbances when these data are considered as part of treatment planning. Prognosis of this pervasive disorder depends on the intellectual abilities: the better intellectual functioning, the possibilities for life adaptation are higherQEEG shows generally increased delta-theta activity in frontal region of the brain which is related to poor cognitive abilities.Brain rate measured in CZ shows slow brain activity related to under arousal.Pharmacotherapy combined with behavior therapy, social support and especially neurofeedback technique promise slight improvements.

Brain profiling and clinical-neuroscience.

PubMed

Peled, Avi

2006-01-01

The current psychiatric diagnostic system, the diagnostic statistic manual, has recently come under increasing criticism. The major reason for the shortcomings of the current psychiatric diagnosis is the lack of a scientific brain-related etiological knowledge about mental disorders. The advancement toward such knowledge is further hampered by the lack of a theoretical framework or "language" that translates clinical findings of mental disorders to brain disturbances and insufficiencies. Here such a theoretical construct is proposed based on insights from neuroscience and neural-computation models. Correlates between clinical manifestations and presumed neuronal network disturbances are proposed in the form of a practical diagnostic system titled "Brain Profiling". Three dimensions make-up brain profiling, "neural complexity disorders", "neuronal resilience insufficiency", and "context-sensitive processing decline". The first dimension relates to disturbances occurring to fast neuronal activations in the millisecond range, it incorporates connectivity and hierarchical imbalances appertaining typically to psychotic and schizophrenic clinical manifestations. The second dimension relates to disturbances that alter slower changes namely long-term synaptic modulations, and incorporates disturbances to optimization and constraint satisfactions within relevant neuronal circuitry. Finally, the level of internal representations related to personality disorders is presented by a "context-sensitive process decline" as the third dimension. For practical use of brain profiling diagnosis a consensual list of psychiatric clinical manifestations provides a "diagnostic input vector", clinical findings are coded 1 for "detection" and 0 for "non-detection", 0.5 is coded for "questionable". The entries are clustered according to their presumed neuronal dynamic relationships and coefficients determine their relevance to the specific related brain disturbance. Relevant equations calculate and normalize the different values attributed to relevant brain disturbances culminating in a three-digit estimation representing the three diagnostic dimensions. brain profiling has the promise for a future brain-related diagnosis. It offers testable predictions about the etiology of mental disorders because being brain-related it lends readily to brain imaging investigations. Being presented also as a one-point representation in a three-dimensional space, multiple follow-up diagnoses trace a trajectory representing an easy-to-see clinical history of the patient. Additional, more immediate, advantages involve reduced stigma because it relaters the disorder to the brain not the person, in addition the three-digit diagnostic code is clinically informative unlike the DSM codes that have no clinical relevance. To conclude, brain profiling diagnosis of mental disorders could be a bold new step toward a "clinical-neuroscience" substituting "psychiatry".

Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

PubMed Central

Dubey, Mohit; Brouwers, Eelke; Hamilton, Eline M.C.; Stiedl, Oliver; Bugiani, Marianna; Koch, Henner; Kole, Maarten H.P.; Boschert, Ursula; Wykes, Robert C.; Mansvelder, Huibert D.; van der Knaap, Marjo S.

2018-01-01

Objective Loss of function of the astrocyte‐specific protein MLC1 leads to the childhood‐onset leukodystrophy “megalencephalic leukoencephalopathy with subcortical cysts” (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking. Methods We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole‐cell patch‐clamp recordings and K+‐sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC. Results An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+ dynamics and neuronal network activity are abnormal in MLC mice. Interpretation Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. Ann Neurol 2018;83:636–649 PMID:29466841

Intestinal microbiota in pathophysiology and management of irritable bowel syndrome

PubMed Central

Lee, Kang Nyeong; Lee, Oh Young

2014-01-01

Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 1014 cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS. PMID:25083061

Disrupted neural processing of emotional faces in psychopathy.

PubMed

Contreras-Rodríguez, Oren; Pujol, Jesus; Batalla, Iolanda; Harrison, Ben J; Bosque, Javier; Ibern-Regàs, Immaculada; Hernández-Ribas, Rosa; Soriano-Mas, Carles; Deus, Joan; López-Solà, Marina; Pifarré, Josep; Menchón, José M; Cardoner, Narcís

2014-04-01

Psychopaths show a reduced ability to recognize emotion facial expressions, which may disturb the interpersonal relationship development and successful social adaptation. Behavioral hypotheses point toward an association between emotion recognition deficits in psychopathy and amygdala dysfunction. Our prediction was that amygdala dysfunction would combine deficient activation with disturbances in functional connectivity with cortical regions of the face-processing network. Twenty-two psychopaths and 22 control subjects were assessed and functional magnetic resonance maps were generated to identify both brain activation and task-induced functional connectivity using psychophysiological interaction analysis during an emotional face-matching task. Results showed significant amygdala activation in control subjects only, but differences between study groups did not reach statistical significance. In contrast, psychopaths showed significantly increased activation in visual and prefrontal areas, with this latest activation being associated with psychopaths' affective-interpersonal disturbances. Psychophysiological interaction analyses revealed a reciprocal reduction in functional connectivity between the left amygdala and visual and prefrontal cortices. Our results suggest that emotional stimulation may evoke a relevant cortical response in psychopaths, but a disruption in the processing of emotional faces exists involving the reciprocal functional interaction between the amygdala and neocortex, consistent with the notion of a failure to integrate emotion into cognition in psychopathic individuals.

Connectomic markers of symptom severity in sport-related concussion: Whole-brain analysis of resting-state fMRI.

PubMed

Churchill, Nathan W; Hutchison, Michael G; Graham, Simon J; Schweizer, Tom A

2018-01-01

Concussion is associated with significant adverse effects within the first week post-injury, including physical complaints and altered cognition, sleep and mood. It is currently unknown whether these subjective disturbances have reliable functional brain correlates. Resting-state functional magnetic resonance imaging (rs-fMRI) has been used to measure functional connectivity of individuals after traumatic brain injury, but less is known about the relationship between functional connectivity and symptom assessments after a sport concussion. In this study, rs-fMRI was used to evaluate whole-brain functional connectivity for seventy (70) university-level athletes, including 35 with acute concussion and 35 healthy matched controls. Univariate analyses showed that greater symptom severity was mainly associated with lower pairwise connectivity in frontal, temporal and insular regions, along with higher connectivity in a sparser set of cerebellar regions. A novel multivariate approach also extracted two components that showed reliable covariation with symptom severity: (1) a network of frontal, temporal and insular regions where connectivity was negatively correlated with symptom severity (replicating the univariate findings); and (2) a network with anti-correlated elements of the default-mode network and sensorimotor system, where connectivity was positively correlated with symptom severity. These findings support the presence of connectomic signatures of symptom complaints following a sport-related concussion, including both increased and decreased functional connectivity within distinct functional brain networks.

The Anatomical Distance of Functional Connections Predicts Brain Network Topology in Health and Schizophrenia

PubMed Central

Vértes, Petra E.; Stidd, Reva; Lalonde, François; Clasen, Liv; Rapoport, Judith; Giedd, Jay; Bullmore, Edward T.; Gogtay, Nitin

2013-01-01

The human brain is a topologically complex network embedded in anatomical space. Here, we systematically explored relationships between functional connectivity, complex network topology, and anatomical (Euclidean) distance between connected brain regions, in the resting-state functional magnetic resonance imaging brain networks of 20 healthy volunteers and 19 patients with childhood-onset schizophrenia (COS). Normal between-subject differences in average distance of connected edges in brain graphs were strongly associated with variation in topological properties of functional networks. In addition, a club or subset of connector hubs was identified, in lateral temporal, parietal, dorsal prefrontal, and medial prefrontal/cingulate cortical regions. In COS, there was reduced strength of functional connectivity over short distances especially, and therefore, global mean connection distance of thresholded graphs was significantly greater than normal. As predicted from relationships between spatial and topological properties of normal networks, this disorder-related proportional increase in connection distance was associated with reduced clustering and modularity and increased global efficiency of COS networks. Between-group differences in connection distance were localized specifically to connector hubs of multimodal association cortex. In relation to the neurodevelopmental pathogenesis of schizophrenia, we argue that the data are consistent with the interpretation that spatial and topological disturbances of functional network organization could arise from excessive “pruning” of short-distance functional connections in schizophrenia. PMID:22275481

Neuroimaging of Narcolepsy and Kleine-Levin Syndrome.

PubMed

Hong, Seung Bong

2017-09-01

Narcolepsy is a chronic neurologic disorder with the abnormal regulation of the sleep-wake cycle, resulting in excessive daytime sleepiness, disturbed nocturnal sleep, and manifestations related to rapid eye movement sleep, such as cataplexy, sleep paralysis, and hypnagogic hallucination. Over the past decade, numerous neuroimaging studies have been performed to characterize the pathophysiology and various clinical features of narcolepsy. This article reviews structural and functional brain imaging findings in narcolepsy and Kleine-Levin syndrome. Based on the current state of research, brain imaging is a useful tool to investigate and understand the neuroanatomic correlates and brain abnormalities of narcolepsy and other hypersomnia. Copyright © 2017 Elsevier Inc. All rights reserved.

[Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

PubMed

Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

Annual Research Review: Progress in Using Brain Morphometry as a Clinical Tool for Diagnosing Psychiatric Disorders

ERIC Educational Resources Information Center

Haubold, Alexander; Peterson, Bradley S.; Bansal, Ravi

2012-01-01

Brain morphometry in recent decades has increased our understanding of the neural bases of psychiatric disorders by localizing anatomical disturbances to specific nuclei and subnuclei of the brain. At least some of these disturbances precede the overt expression of clinical symptoms and possibly are endophenotypes that could be used to diagnose an…

QEEG characteristics and spectrum weighted frequency for children diagnosed as autistic spectrum disorder

PubMed Central

2010-01-01

Background Autistic spectrum disorders are a group of neurological and developmental disorders associated with social, communication, sensory, behavioral and cognitive impairments, as well as restricted, repetitive patterns of behavior, activities, or interests. The aim of this study was a) to analyze QEEG findings of autistic patients and to compare the results with data base; and b) to introduce the calculation of spectrum weighted frequency (brain rate) as an indicator of general mental arousal in these patients. Results Results for Q-EEG shows generally increased delta-theta activity in frontal region of the brain. Changes in QEEG pattern appeared to be in a non-linear correlation with maturational processes. Brain rate measured in CZ shows slow brain activity (5. 86) which is significantly lower than normal and corresponds to low general mental arousal. Recent research has shown that autistic disorders have as their basis disturbances of neural connectivity. Neurofeedback seems capable of remediating such disturbances when these data are considered as part of treatment planning. Conclusions Prognosis of this pervasive disorder depends on the intellectual abilities: the better intellectual functioning, the possibilities for life adaptation are higher QEEG shows generally increased delta-theta activity in frontal region of the brain which is related to poor cognitive abilities. Brain rate measured in CZ shows slow brain activity related to under arousal. Pharmacotherapy combined with behavior therapy, social support and especially neurofeedback technique promise slight improvements PMID:20920283

Severe methylenetetrahydrofolate reductase deficiency in mice results in behavioral anomalies with morphological and biochemical changes in hippocampus.

PubMed

Jadavji, Nafisa M; Deng, Liyuan; Leclerc, Daniel; Malysheva, Olga; Bedell, Barry J; Caudill, Marie A; Rozen, Rima

2012-06-01

The brain is particularly sensitive to folate metabolic disturbances, since methyl groups are critical for its functions. Methylenetetrahydrofolate reductase (MTHFR) generates the primary circulatory form of folate required for homocysteine remethylation to methionine. Neurological disturbances have been described in homocystinuria caused by severe MTHFR deficiency. The goal of this study was to determine if behavioral anomalies are present in severe Mthfr-deficient (Mthfr(-/-)) mice and to identify neurobiological changes that could contribute to these anomalies. Adult male mice of 3 Mthfr genotypes (+/+, +/-, -/-) were tested on motor, anxiety, exploratory and cognitive tasks. Volumes (whole brain and hippocampus) and morphology, global DNA methylation, apoptosis, expression of choline acetyltransferase (ChAT) and glucocorticoid receptor (GR), and concentrations of choline metabolites were assessed in hippocampus. Mthfr(-/-) mice had impairments in motor function and in short- and long-term memory, increased exploratory behavior and decreased anxiety. They showed decreased whole brain and hippocampal volumes, reduced thickness of the pyramidal cell layer of CA1 and CA3, and increased apoptosis in hippocampus. There was a disturbance in choline metabolism as manifested by differences in acetylcholine, betaine or glycerophosphocholine concentrations, and by increased ChAT levels. Mthfr(-/-) mice also had increased GR mRNA and protein. Our study has revealed significant anomalies in affective behavior and impairments in memory of Mthfr(-/-) mice. We identified structural changes, increased apoptosis, altered choline metabolism and GR dysregulation in hippocampus. These findings, as well as some similar observations in cerebellum, could contribute to the behavioral changes and suggest that choline is a critical metabolite in homocystinuria. Copyright © 2012 Elsevier Inc. All rights reserved.

Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics.

PubMed

Baliki, Marwan N; Geha, Paul Y; Apkarian, A Vania; Chialvo, Dante R

2008-02-06

Chronic pain patients suffer from more than just pain; depression and anxiety, sleep disturbances, and decision-making abnormalities (Apkarian et al., 2004a) also significantly diminish their quality of life. Recent studies have demonstrated that chronic pain harms cortical areas unrelated to pain (Apkarian et al., 2004b; Acerra and Moseley, 2005), but whether these structural impairments and behavioral deficits are connected by a single mechanism is as of yet unknown. Here we propose that long-term pain alters the functional connectivity of cortical regions known to be active at rest, i.e., the components of the "default mode network" (DMN). This DMN (Raichle et al., 2001; Greicius et al., 2003; Vincent et al., 2007) is marked by balanced positive and negative correlations between activity in component brain regions. In several disorders, however this balance is disrupted (Fox and Raichle, 2007). Using well validated functional magnetic resonance imaging (fMRI) paradigms to study the DMN (Fox et al., 2005), we investigated whether the impairments of chronic pain patients could be rooted in disturbed DMN dynamics. Studying with fMRI a group of chronic back pain (CBP) patients and healthy controls while executing a simple visual attention task, we discovered that CBP patients, despite performing the task equally well as controls, displayed reduced deactivation in several key DMN regions. These findings demonstrate that chronic pain has a widespread impact on overall brain function, and suggest that disruptions of the DMN may underlie the cognitive and behavioral impairments accompanying chronic pain.

Toward a complex system understanding of bipolar disorder: A chaotic model of abnormal circadian activity rhythms in euthymic bipolar disorder.

PubMed

Hadaeghi, Fatemeh; Hashemi Golpayegani, Mohammad Reza; Jafari, Sajad; Murray, Greg

2016-08-01

In the absence of a comprehensive neural model to explain the underlying mechanisms of disturbed circadian function in bipolar disorder, mathematical modeling is a helpful tool. Here, circadian activity as a response to exogenous daily cycles is proposed to be the product of interactions between neuronal networks in cortical (cognitive processing) and subcortical (pacemaker) areas of the brain. To investigate the dynamical aspects of the link between disturbed circadian activity rhythms and abnormalities of neurotransmitter functioning in frontal areas of the brain, we developed a novel mathematical model of a chaotic system which represents fluctuations in circadian activity in bipolar disorder as changes in the model's parameters. A novel map-based chaotic system was developed to capture disturbances in circadian activity across the two extreme mood states of bipolar disorder. The model uses chaos theory to characterize interplay between neurotransmitter functions and rhythm generation; it aims to illuminate key activity phenomenology in bipolar disorder, including prolonged sleep intervals, decreased total activity and attenuated amplitude of the diurnal activity rhythm. To test our new cortical-circadian mathematical model of bipolar disorder, we utilized previously collected locomotor activity data recorded from normal subjects and bipolar patients by wrist-worn actigraphs. All control parameters in the proposed model have an important role in replicating the different aspects of circadian activity rhythm generation in the brain. The model can successfully replicate deviations in sleep/wake time intervals corresponding to manic and depressive episodes of bipolar disorder, in which one of the excitatory or inhibitory pathways is abnormally dominant. Although neuroimaging research has strongly implicated a reciprocal interaction between cortical and subcortical regions as pathogenic in bipolar disorder, this is the first model to mathematically represent this multilevel explanation of the phenomena of bipolar disorder. © The Royal Australian and New Zealand College of Psychiatrists 2016.

Mouse model for deficiency of methionine synthase reductase exhibits short-term memory impairment and disturbances in brain choline metabolism.

PubMed

Jadavji, Nafisa M; Bahous, Renata H; Deng, Liyuan; Malysheva, Olga; Grand'maison, Marilyn; Bedell, Barry J; Caudill, Marie A; Rozen, Rima

2014-07-15

Hyperhomocysteinaemia can contribute to cognitive impairment and brain atrophy. MTRR (methionine synthase reductase) activates methionine synthase, which catalyses homocysteine remethylation to methionine. Severe MTRR deficiency results in homocystinuria with cognitive and motor impairments. An MTRR polymorphism may influence homocysteine levels and reproductive outcomes. The goal of the present study was to determine whether mild hyperhomocysteinaemia affects neurological function in a mouse model with Mtrr deficiency. Mtrr+/+, Mtrr+/gt and Mtrrgt/gt mice (3 months old) were assessed for short-term memory, brain volumes and hippocampal morphology. We also measured DNA methylation, apoptosis, neurogenesis, choline metabolites and expression of ChAT (choline acetyltransferase) and AChE (acetylcholinesterase) in the hippocampus. Mtrrgt/gt mice exhibited short-term memory impairment on two tasks. They had global DNA hypomethylation and decreased choline, betaine and acetylcholine levels. Expression of ChAT and AChE was increased and decreased respectively. At 3 weeks of age, they showed increased neurogenesis. In the cerebellum, mutant mice had DNA hypomethylation, decreased choline and increased expression of ChAT. Our work demonstrates that mild hyperhomocysteinaemia is associated with memory impairment. We propose a mechanism whereby a deficiency in methionine synthesis leads to hypomethylation and compensatory disturbances in choline metabolism in the hippocampus. This disturbance affects the levels of acetylcholine, a critical neurotransmitter in learning and memory.

Different shades of default mode disturbance in schizophrenia: Subnodal covariance estimation in structure and function.

PubMed

Lefort-Besnard, Jérémy; Bassett, Danielle S; Smallwood, Jonathan; Margulies, Daniel S; Derntl, Birgit; Gruber, Oliver; Aleman, Andre; Jardri, Renaud; Varoquaux, Gaël; Thirion, Bertrand; Eickhoff, Simon B; Bzdok, Danilo

2018-02-01

Schizophrenia is a devastating mental disease with an apparent disruption in the highly associative default mode network (DMN). Interplay between this canonical network and others probably contributes to goal-directed behavior so its disturbance is a candidate neural fingerprint underlying schizophrenia psychopathology. Previous research has reported both hyperconnectivity and hypoconnectivity within the DMN, and both increased and decreased DMN coupling with the multimodal saliency network (SN) and dorsal attention network (DAN). This study systematically revisited network disruption in patients with schizophrenia using data-derived network atlases and multivariate pattern-learning algorithms in a multisite dataset (n = 325). Resting-state fluctuations in unconstrained brain states were used to estimate functional connectivity, and local volume differences between individuals were used to estimate structural co-occurrence within and between the DMN, SN, and DAN. In brain structure and function, sparse inverse covariance estimates of network coupling were used to characterize healthy participants and patients with schizophrenia, and to identify statistically significant group differences. Evidence did not confirm that the backbone of the DMN was the primary driver of brain dysfunction in schizophrenia. Instead, functional and structural aberrations were frequently located outside of the DMN core, such as in the anterior temporoparietal junction and precuneus. Additionally, functional covariation analyses highlighted dysfunctional DMN-DAN coupling, while structural covariation results highlighted aberrant DMN-SN coupling. Our findings reframe the role of the DMN core and its relation to canonical networks in schizophrenia. We thus underline the importance of large-scale neural interactions as effective biomarkers and indicators of how to tailor psychiatric care to single patients. © 2017 Wiley Periodicals, Inc.

[A novel proposal explaining sleep disturbance of children in Japan--asynchronization].

PubMed

Kohyama, Jun

2008-07-01

It has been reported that more than half of the children in Japan suffer from daytime sleepiness. In contrast, about one quarter of junior high-school students in Japan complain of insomnia. According to the International Classification of Sleep Disorders (Second edition), these children could be diagnosed as having behaviorally-induced insufficient sleep syndrome due to inadequate sleeping habits. Getting on adequate amount of sleep should solve such problems;however, such a therapeutic approach often fails. Although social factors are involved in these sleep disturbances, I feel that a novel notion - asynchronization - leads to an understanding of the pathophysiology of disturbances in these children. Further, it could contribute to resolve their problems. The essence of asynchronization is a disturbance of various aspects (e.g., cycle, amplitude, phase, and interrelationship) of the biological rhythms that normally exhibits circadian oscillation. The main cause of asynchronization is hypothesized to be the combination of light exposure during night and the lack of light exposure in the morning. Asynchronization results in the disturbance of variable systems. Thus, symptoms of asynchronization include disturbances of the autonomic nervous system (sleepiness, insomnia, disturbance of hormonal excretion, gastrointestinal problems, etc.) and higher brain function (disorientation, loss of sociality, loss of will or motivation, impaired alertness and performance, etc.). Neurological (attention deficit, aggression, impulsiveness, hyperactivity, etc.), psychiatric (depressive disorders, personality disorders, anxiety disorders, etc.) and somatic (tiredness, fatigue, etc.) disturbances could also be symptoms of asynchronization. At the initial phase of asynchronization, disturbances are functional and can be resolved relatively easily, such as by the establishment of a regular sleep-wakefulness cycle;however, without adequate intervention the disturbances could gradually worsen and become hard to resolve.

Stuck in a State of Inattention? Functional Hyperconnectivity as an Indicator of Disturbed Intrinsic Brain Dynamics in Adolescents With Concussion: A Pilot Study

PubMed Central

Virji-Babul, Naznin

2018-01-01

Sports-related concussion in youth is a major public health issue. Evaluating the diffuse and often subtle changes in structure and function that occur in the brain, particularly in this population, remains a significant challenge. The goal of this pilot study was to evaluate the relationship between the intrinsic dynamics of the brain using resting-state functional magnetic resonance imaging (rs-fMRI) and relate these findings to structural brain correlates from diffusion tensor imaging in a group of adolescents with sports-related concussions (n = 6) and a group of healthy adolescent athletes (n = 6). We analyzed rs-fMRI data using a sliding windows approach and related the functional findings to structural brain correlates by applying graph theory analysis to the diffusion tensor imaging data. Within the resting-state condition, we extracted three separate brain states in both groups. Our analysis revealed that the brain dynamics in healthy adolescents was characterized by a dynamic pattern, shifting equally between three brain states; however, in adolescents with concussion, the pattern was more static with a longer time spent in one brain state. Importantly, this lack of dynamic flexibility in the concussed group was associated with increased nodal strength in the left middle frontal gyrus, suggesting reorganization in a region related to attention. This preliminary report shows that both the intrinsic brain dynamics and structural organization are altered in networks related to attention in adolescents with concussion. This first report in adolescents will be used to inform future studies in a larger cohort. PMID:29357675

Stuck in a State of Inattention? Functional Hyperconnectivity as an Indicator of Disturbed Intrinsic Brain Dynamics in Adolescents With Concussion: A Pilot Study.

PubMed

Muller, Angela M; Virji-Babul, Naznin

2018-01-01

Sports-related concussion in youth is a major public health issue. Evaluating the diffuse and often subtle changes in structure and function that occur in the brain, particularly in this population, remains a significant challenge. The goal of this pilot study was to evaluate the relationship between the intrinsic dynamics of the brain using resting-state functional magnetic resonance imaging (rs-fMRI) and relate these findings to structural brain correlates from diffusion tensor imaging in a group of adolescents with sports-related concussions ( n = 6) and a group of healthy adolescent athletes ( n = 6). We analyzed rs-fMRI data using a sliding windows approach and related the functional findings to structural brain correlates by applying graph theory analysis to the diffusion tensor imaging data. Within the resting-state condition, we extracted three separate brain states in both groups. Our analysis revealed that the brain dynamics in healthy adolescents was characterized by a dynamic pattern, shifting equally between three brain states; however, in adolescents with concussion, the pattern was more static with a longer time spent in one brain state. Importantly, this lack of dynamic flexibility in the concussed group was associated with increased nodal strength in the left middle frontal gyrus, suggesting reorganization in a region related to attention. This preliminary report shows that both the intrinsic brain dynamics and structural organization are altered in networks related to attention in adolescents with concussion. This first report in adolescents will be used to inform future studies in a larger cohort.

Forthergillian Lecture. Imaging human brain function.

PubMed

Frackowiak, R S

The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning plastic change. Other models of plastic change, such as normal visuospatial learning or re-establishing speech comprehension after cochlear implantation in the deaf illustrate how patterns of brain function adapt over time. Limitations of the scanning techniques and prospects for the future are discussed in relation to new developments in the neuroimaging field.

Imaging functional and structural brain connectomics in attention-deficit/hyperactivity disorder.

PubMed

Cao, Miao; Shu, Ni; Cao, Qingjiu; Wang, Yufeng; He, Yong

2014-12-01

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopment disorders in childhood. Clinically, the core symptoms of this disorder include inattention, hyperactivity, and impulsivity. Previous studies have documented that these behavior deficits in ADHD children are associated with not only regional brain abnormalities but also changes in functional and structural connectivity among regions. In the past several years, our understanding of how ADHD affects the brain's connectivity has been greatly advanced by mapping topological alterations of large-scale brain networks (i.e., connectomes) using noninvasive neurophysiological and neuroimaging techniques (e.g., electroencephalograph, functional MRI, and diffusion MRI) in combination with graph theoretical approaches. In this review, we summarize the recent progresses of functional and structural brain connectomics in ADHD, focusing on graphic analysis of large-scale brain systems. Convergent evidence suggests that children with ADHD had abnormal small-world properties in both functional and structural brain networks characterized by higher local clustering and lower global integrity, suggesting a disorder-related shift of network topology toward regular configurations. Moreover, ADHD children showed the redistribution of regional nodes and connectivity involving the default-mode, attention, and sensorimotor systems. Importantly, these ADHD-associated alterations significantly correlated with behavior disturbances (e.g., inattention and hyperactivity/impulsivity symptoms) and exhibited differential patterns between clinical subtypes. Together, these connectome-based studies highlight brain network dysfunction in ADHD, thus opening up a new window into our understanding of the pathophysiological mechanisms of this disorder. These works might also have important implications on the development of imaging-based biomarkers for clinical diagnosis and treatment evaluation in ADHD.

Neuroimaging in pedophilia.

PubMed

Wiebking, Christine; Northoff, Georg

2013-04-01

Paraphilia is a set of disorders characterized by abnormal sexual desires. Perhaps most discussed amongst them, pedophilia is a complex interaction of disturbances of the emotional, cognitive and sexual experience. Using new imaging techniques such as functional magnetic resonance imaging, neural correlates of emotional, sexual and cognitive abnormalities and interactions have been investigated. As described on the basis of current research, altered patterns of brain activity, especially in the frontal areas of the brain, are seen in pedophilia. Building on these results, the analysis of neural correlates of impaired psychological functions opens the opportunity to further explore sexual deviances, which may contribute ultimately to the development of tools for risk assessment, classification methods and new therapeutic approaches.

Alexithymia decreases altruism in real social decisions.

PubMed

Feldmanhall, Oriel; Dalgleish, Tim; Mobbs, Dean

2013-03-01

Alexithymia, a sub-clinical personality construct associated with disturbances in affect regulation and social functioning, is known to be comorbid with a number of psychiatric conditions. We combined a distressing real-time altruism task with functional magnetic resonance imagining to explore the brain behaviour relationship between alexithymia and prosocial action. Here we show that individuals high on the alexithymia spectrum report less distress at seeing others in pain and behave less altruistically. This behavioural result is mirrored in the brain, where individuals who have difficulty recognizing and experiencing others' emotional distress have reduced neural activation within the anterior insula and temporoparietal junction, key regions in the experience of distress and perspective-taking. Copyright © 2012 Elsevier Ltd. All rights reserved.

Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

PubMed Central

Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark

2015-01-01

Abstract Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were prospectively recruited from the emergency department of our local Level-1 trauma center for an advanced MRI scan at the acute stage. Sixteen age- and sex-matched controls were also recruited for comparison. Both group-based and individual-based independent component analysis of resting-state fMRI (rsfMRI) demonstrated reduced functional connectivity in both posterior cingulate cortex (PCC) and precuneus regions in comparison with controls, which is part of the default mode network (DMN). Further seed-based analysis confirmed reduced functional connectivity in these two regions and also demonstrated increased connectivity between these regions and other regions of the brain in mTBI. Seed-based analysis using the thalamus, hippocampus, and amygdala regions further demonstrated increased functional connectivity between these regions and other regions of the brain, particularly in the frontal lobe, in mTBI. Our data demonstrate alterations of multiple brain networks at the resting state, particularly increased functional connectivity in the frontal lobe, in response to brain concussion at the acute stage. Resting-state functional connectivity of the DMN could serve as a potential biomarker for improved detection of mTBI in the acute setting. PMID:25285363

Luria revisited: cognitive research in schizophrenia, past implications and future challenges.

PubMed

Zaytseva, Yuliya; Chan, Raymond C K; Pöppel, Ernst; Heinz, Andreas

2015-02-27

Contemporary psychiatry is becoming more biologically oriented in the attempt to elicit a biological rationale of mental diseases. Although mental disorders comprise mostly functional abnormalities, there is a substantial overlap between neurology and psychiatry in addressing cognitive disturbances. In schizophrenia, the presence of cognitive impairment prior to the onset of psychosis and early after its manifestation suggests that some neurocognitive abnormalities precede the onset of psychosis and may represent a trait marker. These cognitive alterations may arise from functional disconnectivity, as no significant brain damage has been found. In this review we aim to revise A.R. Luria's systematic approach used in the neuropsychological evaluation of cognitive functions, which was primarily applied in patients with neurological disorders and in the cognitive evaluation in schizophrenia and other related disorders. As proposed by Luria, cognitive processes, associated with higher cortical functions, may represent functional systems that are not localized in narrow, circumscribed areas of the brain, but occur among groups of concertedly working brain structures, each of which makes its own particular contribution to the organization of the functional system. Current developments in neuroscience provide evidence of functional connectivity in the brain. Therefore, Luria's approach may serve as a frame of reference for the analysis and interpretation of cognitive functions in general and their abnormalities in schizophrenia in particular. Having said that, modern technology, as well as experimental evidence, may help us to understand the brain better and lead us towards creating a new classification of cognitive functions. In schizophrenia research, multidisciplinary approaches must be utilized to address specific cognitive alterations. The relationships among the components of cognitive functions derived from the functional connectivity of the brain may provide an insight into cognitive machinery.

Abdominal pain in Irritable Bowel Syndrome: a review of putative psychological, neural and neuro-immune mechanisms.

PubMed

Elsenbruch, Sigrid

2011-03-01

Chronic abdominal pain is a common symptom of great clinical significance in several areas of medicine. In many cases no organic cause can be established resulting in the classification as functional gastrointestinal disorder. Irritable Bowel Syndrome (IBS) is the most common of these conditions and is considered an important public health problem because it can be disabling and constitutes a major social and economic burden given the lack of effective treatments. IBS aetiology is most likely multi-factorial involving biological, psychological and social factors. Visceral hyperalgesia (or hypersensitivity) and visceral hypervigilance, which could be mediated by peripheral, spinal, and/or central pathways, constitute key concepts in current research on pathophysiological mechanisms of visceral hyperalgesia. The role of central nervous system mechanisms along the "brain-gut axis" is increasingly appreciated, owing to accumulating evidence from brain imaging studies that neural processing of visceral stimuli is altered in IBS together with long-standing knowledge regarding the contribution of stress and negative emotions to symptom frequency and severity. At the same time, there is also growing evidence suggesting that peripheral immune mechanisms and disturbed neuro-immune communication could play a role in the pathophysiology of visceral hyperalgesia. This review presents recent advances in research on the pathophysiology of visceral hyperalgesia in IBS, with a focus on the role of stress and anxiety in central and peripheral response to visceral pain stimuli. Together, these findings support that in addition to lower pain thresholds displayed by a significant proportion of patients, the evaluation of pain appears to be altered in IBS. This may be attributable to affective disturbances, negative emotions in anticipation of or during visceral stimulation, and altered pain-related expectations and learning processes. Disturbed "top-down" emotional and cognitive pain modulation in IBS is reflected by functional and possibly structural brain changes involving prefrontal as well as cingulate regions. At the same time, there is growing evidence linking peripheral and mucosal immune changes and abdominal pain in IBS, supporting disturbed peripheral pain signalling. Findings in post-infectious IBS emphasize the interaction between centrally-mediated psychosocial risk factors and local inflammation in predicting long-term IBS symptoms. Investigating afferent immune-to-brain communication in visceral hyperalgesia as a component of the sickness response constitutes a promising future research goal. Copyright © 2010 Elsevier Inc. All rights reserved.

Application of Awake Craniotomy and Intraoperative Brain Mapping for Surgical Resection of Insular Gliomas of the Dominant Hemisphere.

PubMed

Alimohamadi, Maysam; Shirani, Mohammad; Shariat Moharari, Reza; Pour-Rashidi, Ahmad; Ketabchi, Mehdi; Khajavi, Mohammadreza; Arami, Mohamadali; Amirjamshidi, Abbas

2016-08-01

Radical resection of dominant insular gliomas is difficult because of their close vicinity with internal capsule, basal ganglia, and speech centers. Brain mapping techniques can be used to maximize the extent of tumor removal and to minimize postoperative morbidities by precise localization of eloquent cortical and subcortical areas. Patients with newly diagnosed gliomas of dominant insula were enrolled. The exclusion criteria were severe cognitive disturbances, communication difficulty, age greater than 75 years, severe obesity, difficult airways for intubation and severe cardiopulmonary diseases. All were evaluated preoperatively with contrast-enhanced brain magnetic resonance imaging (MRI), functional brain MRI, and diffusion tensor tractography of language and motor systems. All underwent awake craniotomy with the same anesthesiology protocol. Intraoperative monitoring included continuous motor-evoked potential, electromyography, electrocorticography, direct electrical stimulation of cortex, and subcortical tracts. The patients were followed with serial neurologic examination and imaging. Ten patients were enrolled (4 men, 6 women) with a mean age of 43.6 years. Seven patients suffered from low-grade glioma, and 3 patients had high-grade glioma. The most common clinical presentation was seizure followed by speech disturbance, hemiparesis, and memory loss. Extent of tumor resection ranged from 73% to 100%. No mortality or new major postoperative neurologic deficit was encountered. Seizure control improved in three fourths of patients with medical refractory epilepsy. In one patient with speech disorder at presentation, the speech problem became worse after surgery. Brain mapping during awake craniotomy helps to maximize extent of tumor resection while preserving neurologic function in patients with dominant insular lobe glioma. Copyright © 2016. Published by Elsevier Inc.

Noninvasive and painless magnetic stimulation of nerves improved brain motor function and mobility in a cerebral palsy case.

PubMed

Flamand, Véronique H; Schneider, Cyril

2014-10-01

Motor deficits in cerebral palsy disturb functional independence. This study tested whether noninvasive and painless repetitive peripheral magnetic stimulation could improve motor function in a 7-year-old boy with spastic hemiparetic cerebral palsy. Stimulation was applied over different nerves of the lower limbs for 5 sessions. We measured the concurrent aftereffects of this intervention on ankle motor control, gait (walking velocity, stride length, cadence, cycle duration), and function of brain motor pathways. We observed a decrease of ankle plantar flexors resistance to stretch, an increase of active dorsiflexion range of movement, and improvements of corticospinal control of ankle dorsiflexors. Joint mobility changes were still present 15 days after the end of stimulation, when all gait parameters were also improved. Resistance to stretch was still lower than prestimulation values 45 days after the end of stimulation. This case illustrates the sustained effects of repetitive peripheral magnetic stimulation on brain plasticity, motor function, and gait. It suggests a potential impact for physical rehabilitation in cerebral palsy. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Altered brain long-range functional interactions underlying the link between aberrant self-experience and self-other relationship in first-episode schizophrenia.

PubMed

Ebisch, Sjoerd J H; Mantini, Dante; Northoff, Georg; Salone, Anatolia; De Berardis, Domenico; Ferri, Francesca; Ferro, Filippo M; Di Giannantonio, Massimo; Romani, Gian L; Gallese, Vittorio

2014-09-01

Self-experience anomalies are elementary features of schizophrenic pathology. Such deficits can have a profound impact on self-other relationship, but how they are related through aberrant brain function remains poorly understood. In this functional magnetic resonance imaging (fMRI) study, we provide new evidence for a cortical link between aberrant self-experience and social cognition in first-episode schizophrenia (FES). As identified in previous studies, ventral premotor cortex (vPMC) and posterior insula (pIC) are candidate brain regions underlying disturbances in both self-experience and self-other relationship due to their processing of predominantly externally guided (vPMC; goal-oriented behavior) and internally guided (pIC; interoception) stimuli. Results from functional interaction analysis in a sample of 24 FES patients and 22 healthy controls show aberrant functional interactions (background/intrinsic connectivity) of right vPMC and bilateral pIC with posterior cingulate cortex (PCC), a midline region that has been shown central in mediating self-experience. More specifically, our results show increased functional coupling between vPMC and PCC, which positively correlated with basic symptoms (subjective self-experience disturbances). pIC showed reduced functional coupling with PCC and postcentral gyrus and increased functional interactions with anterior insula. Taken together, our results suggest an imbalance in the processing between internally and externally guided information and its abnormal integration with self-referential processing as mediated by PCC. Due to our correlation findings, we suggest this imbalance to be closely related to basic symptoms in FES and thus anomalous self-experience. The findings further disentangle the cortical basis of how self-experience anomalies may pervade the social domain. © The Author 2013. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Emotional and personality changes following brain tumour resection.

PubMed

Jenkins, Lisanne M; Drummond, Katharine J; Andrewes, David G

2016-07-01

Psychological distress has a high prevalence in brain tumour patients, and understanding the emotional and personality changes that may follow neurosurgery is important for clinical management of these patients. We aimed to characterise these emotional and personality changes using subjective, observer-rated and clinical measures. We examined subjective changes in emotional experience and observer-rated changes to personality disturbances following neurosurgery for brain tumours (n=44), compared to a control group that had undergone spinal surgery (n=26). Participants completed the Hospital Anxiety and Depression Scale and a Subjective Emotional Change Questionnaire. Observers who knew the patients well also completed the Iowa Rating Scale of Personality Change. Compared to controls, patients with tumours reported significantly more changes to their subjective experience of emotions following neurosurgery, particularly anger, disgust and sadness. For the observer-ratings, tumour patients were described as having significant changes in the personality disturbances of irritability, impulsivity, moodiness, inflexibility, and being easily overwhelmed. Anxiety and depression were not significantly different between groups. Neurosurgical resection of a brain tumour is a major life event that changes patients' subjective experiences of different emotions, and leads to observer-rated changes in personality. In this study, these changes were not accompanied by increases in anxiety or depression. We conclude with a discussion of biological and psychosocial mechanisms that can impact emotional functioning and personality in patients with brain tumours. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cardiovascular and respiratory dynamics during normal and pathological sleep

NASA Astrophysics Data System (ADS)

Penzel, Thomas; Wessel, Niels; Riedl, Maik; Kantelhardt, Jan W.; Rostig, Sven; Glos, Martin; Suhrbier, Alexander; Malberg, Hagen; Fietze, Ingo

2007-03-01

Sleep is an active and regulated process with restorative functions for physical and mental conditions. Based on recordings of brain waves and the analysis of characteristic patterns and waveforms it is possible to distinguish wakefulness and five sleep stages. Sleep and the sleep stages modulate autonomous nervous system functions such as body temperature, respiration, blood pressure, and heart rate. These functions consist of a sympathetic tone usually related to activation and to parasympathetic (or vagal) tone usually related to inhibition. Methods of statistical physics are used to analyze heart rate and respiration to detect changes of the autonomous nervous system during sleep. Detrended fluctuation analysis and synchronization analysis and their applications to heart rate and respiration during sleep in healthy subjects and patients with sleep disorders are presented. The observed changes can be used to distinguish sleep stages in healthy subjects as well as to differentiate normal and disturbed sleep on the basis of heart rate and respiration recordings without direct recording of brain waves. Of special interest are the cardiovascular consequences of disturbed sleep because they present a risk factor for cardiovascular disorders such as arterial hypertension, cardiac ischemia, sudden cardiac death, and stroke. New derived variables can help to find indicators for these health risks.

Effect of Error Augmentation on Brain Activation and Motor Learning of a Complex Locomotor Task

PubMed Central

Marchal-Crespo, Laura; Michels, Lars; Jaeger, Lukas; López-Olóriz, Jorge; Riener, Robert

2017-01-01

Up to date, the functional gains obtained after robot-aided gait rehabilitation training are limited. Error augmenting strategies have a great potential to enhance motor learning of simple motor tasks. However, little is known about the effect of these error modulating strategies on complex tasks, such as relearning to walk after a neurologic accident. Additionally, neuroimaging evaluation of brain regions involved in learning processes could provide valuable information on behavioral outcomes. We investigated the effect of robotic training strategies that augment errors—error amplification and random force disturbance—and training without perturbations on brain activation and motor learning of a complex locomotor task. Thirty-four healthy subjects performed the experiment with a robotic stepper (MARCOS) in a 1.5 T MR scanner. The task consisted in tracking a Lissajous figure presented on a display by coordinating the legs in a gait-like movement pattern. Behavioral results showed that training without perturbations enhanced motor learning in initially less skilled subjects, while error amplification benefited better-skilled subjects. Training with error amplification, however, hampered transfer of learning. Randomly disturbing forces induced learning and promoted transfer in all subjects, probably because the unexpected forces increased subjects' attention. Functional MRI revealed main effects of training strategy and skill level during training. A main effect of training strategy was seen in brain regions typically associated with motor control and learning, such as, the basal ganglia, cerebellum, intraparietal sulcus, and angular gyrus. Especially, random disturbance and no perturbation lead to stronger brain activation in similar brain regions than error amplification. Skill-level related effects were observed in the IPS, in parts of the superior parietal lobe (SPL), i.e., precuneus, and temporal cortex. These neuroimaging findings indicate that gait-like motor learning depends on interplay between subcortical, cerebellar, and fronto-parietal brain regions. An interesting observation was the low activation observed in the brain's reward system after training with error amplification compared to training without perturbations. Our results suggest that to enhance learning of a locomotor task, errors should be augmented based on subjects' skill level. The impacts of these strategies on motor learning, brain activation, and motivation in neurological patients need further investigation. PMID:29021739

What is special about the adolescent (JME) brain?

PubMed

Craiu, Dana

2013-07-01

Juvenile myoclonic epilepsy (JME) involves cortico-thalamo-cortical networks. Thalamic, frontal gray matter, connectivity, and neurotransmitter disturbances have been demonstrated by structural/functional imaging studies. Few patients with JME show mutations in genes coding ion channels or GABAA (gamma-aminobutyric acid) receptor subunits. Recent research points to EFHC1 gene mutations leading to microdysgenesis and possible aberrant circuitry. Imaging studies have shown massive structural/functional changes of normally developing adolescent brain structures maturing at strikingly different rates and times. Gray matter (GM) volume diminishes in cortical areas (frontal and parietal) and deep structures (anterior thalamus, putamen, and caudate). Diffusion tensor imaging (DTI) findings support continued microstructural change in WM (white matter) during late adolescence with robust developmental changes in thalamocortical connectivity. The GABAA receptor distribution and specific receptor subunits' expression patterns change with age from neonate to adolescent/adult, contributing to age-related changes in brain excitability. Hormonal influence on brain structure development during adolescence is presented. Possible implications of brain changes during adolescence on the course of JME are discussed. Copyright © 2012 Elsevier Inc. All rights reserved.

Of Microbes and Minds: A Narrative Review on the Second Brain Aging.

PubMed

Calvani, Riccardo; Picca, Anna; Lo Monaco, Maria Rita; Landi, Francesco; Bernabei, Roberto; Marzetti, Emanuele

2018-01-01

In recent years, an extensive body of literature focused on the gut-brain axis and the possible role played by the gut microbiota in modulating brain morphology and function from birth to old age. Gut microbiota has been proposed as a relevant player during the early phases of neurodevelopment, with possible long-standing effects in later life. The reduction in gut microbiota diversity has also become one of the hallmarks of aging, and disturbances in its composition are associated with several (age-related) neurological conditions, including depression, Alzheimer's disease, and Parkinson's disease. Several pathways have been evoked for gut microbiota-brain communication, including neural connections (vagus nerve), circulating mediators derived by host-bacteria cometabolism, as well as the influence exerted by gut microbiota on host gut function, metabolism, and immune system. Although the most provoking data emerged from animal studies and despite the huge debate around the possible epiphenomenal nature of those findings, the gut microbiota-brain axis still remains a fascinating target to be exploited to attenuate some of the most burdensome consequences of aging.

A Complex Interplay of Vitamin B1 and B6 Metabolism with Cognition, Brain Structure, and Functional Connectivity in Older Adults.

PubMed

Jannusch, Kai; Jockwitz, Christiane; Bidmon, Hans-Jürgen; Moebus, Susanne; Amunts, Katrin; Caspers, Svenja

2017-01-01

Aging is associated with brain atrophy, functional brain network reorganization and decline of cognitive performance, albeit characterized by high interindividual variability. Among environmental influencing factors accounting for this variability, nutrition and particularly vitamin supply is thought to play an important role. While evidence exists that supplementation of vitamins B6 and B1 might be beneficial for cognition and brain structure, at least in deficient states and neurodegenerative diseases, little is known about this relation during healthy aging and in relation to reorganization of functional brain networks. We thus assessed the relation between blood levels of vitamins B1 and B6 and cognitive performance, cortical folding, and functional resting-state connectivity in a large sample of older adults ( N > 600; age: 55-85 years), drawn from the population-based 1000BRAINS study. In addition to blood sampling, subjects underwent structural and functional resting-state neuroimaging as well as extensive neuropsychological testing in the domains of executive functions, (working) memory, attention, and language. Brain regions showing changes in the local gyrification index as calculated using FreeSurfer in relation to vitamin levels were used for subsequent seed-based resting-state functional connectivity analysis. For B6, a positive correlation with local cortical folding was found throughout the brain, while only slight changes in functional connectivity were observed. Contrarily, for B1, a negative correlation with cortical folding as well as problem solving and visuo-spatial working memory performance was found, which was accompanied by pronounced increases of interhemispheric and decreases of intrahemispheric functional connectivity. While the effects for B6 expand previous knowledge on beneficial effects of B6 supplementation on brain structure, they also showed that additional effects on cognition might not be recognizable in healthy older subjects with normal B6 blood levels. The cortical atrophy and pronounced functional reorganization associated with B1, contrarily, was more in line with the theory of a disturbed B1 metabolism in older adults, leading to B1 utilization deficits, and thus, an effective B1 deficiency in the brain, despite normal to high-normal blood levels.

A Complex Interplay of Vitamin B1 and B6 Metabolism with Cognition, Brain Structure, and Functional Connectivity in Older Adults

PubMed Central

Jannusch, Kai; Jockwitz, Christiane; Bidmon, Hans-Jürgen; Moebus, Susanne; Amunts, Katrin; Caspers, Svenja

2017-01-01

Aging is associated with brain atrophy, functional brain network reorganization and decline of cognitive performance, albeit characterized by high interindividual variability. Among environmental influencing factors accounting for this variability, nutrition and particularly vitamin supply is thought to play an important role. While evidence exists that supplementation of vitamins B6 and B1 might be beneficial for cognition and brain structure, at least in deficient states and neurodegenerative diseases, little is known about this relation during healthy aging and in relation to reorganization of functional brain networks. We thus assessed the relation between blood levels of vitamins B1 and B6 and cognitive performance, cortical folding, and functional resting-state connectivity in a large sample of older adults (N > 600; age: 55–85 years), drawn from the population-based 1000BRAINS study. In addition to blood sampling, subjects underwent structural and functional resting-state neuroimaging as well as extensive neuropsychological testing in the domains of executive functions, (working) memory, attention, and language. Brain regions showing changes in the local gyrification index as calculated using FreeSurfer in relation to vitamin levels were used for subsequent seed-based resting-state functional connectivity analysis. For B6, a positive correlation with local cortical folding was found throughout the brain, while only slight changes in functional connectivity were observed. Contrarily, for B1, a negative correlation with cortical folding as well as problem solving and visuo-spatial working memory performance was found, which was accompanied by pronounced increases of interhemispheric and decreases of intrahemispheric functional connectivity. While the effects for B6 expand previous knowledge on beneficial effects of B6 supplementation on brain structure, they also showed that additional effects on cognition might not be recognizable in healthy older subjects with normal B6 blood levels. The cortical atrophy and pronounced functional reorganization associated with B1, contrarily, was more in line with the theory of a disturbed B1 metabolism in older adults, leading to B1 utilization deficits, and thus, an effective B1 deficiency in the brain, despite normal to high-normal blood levels. PMID:29163003

Exon Microarray Analysis of Human Dorsolateral Prefrontal Cortex in Alcoholism

PubMed Central

Manzardo, Ann M.; Gunewardena, Sumedha; Wang, Kun; Butler, Merlin G.

2014-01-01

Background Alcohol abuse is associated with cellular and biochemical disturbances that impact upon protein and nucleic acid synthesis, brain development, function and behavioral responses. To further characterize the genetic influences in alcoholism and the effects of alcohol consumption on gene expression, we used a highly sensitive exon microarray to examine mRNA expression in human frontal cortex of alcoholics and control males. Methods Messenger RNA was isolated from the dorsolateral prefrontal cortex (dlPFC, Brodmann area 9) of 7 adult Alcoholic (6 males, 1 female, mean age 48 years) and 7 matched controls. Affymetrix Human Exon 1.0 ST Array was performed according to standard procedures and the results analyzed at the gene level. Microarray findings were validated using qRT-PCR, and the ontology of disturbed genes characterized using Ingenuity Pathway Analysis (IPA). Results Decreased mRNA expression was observed for genes involved in cellular adhesion (e.g., CTNNA3, ITGA2), transport (e.g., TF, ABCA8), nervous system development (e.g., LRP2, UGT8, GLDN) and signaling (e.g., RASGRP, LGR5) with influence over lipid and myelin synthesis (e.g., ASPA, ENPP2, KLK6). IPA identified disturbances in network functions associated with neurological disease, and development including cellular assembly and organization impacting on psychological disorders. Conclusions Our data in alcoholism support a reduction in expression of dlPFC mRNA for genes involved with neuronal growth, differentiation and signaling that targets white matter of the brain. PMID:24890784

Exon microarray analysis of human dorsolateral prefrontal cortex in alcoholism.

PubMed

Manzardo, Ann M; Gunewardena, Sumedha; Wang, Kun; Butler, Merlin G

2014-06-01

Alcohol abuse is associated with cellular and biochemical disturbances that impact upon protein and nucleic acid synthesis, brain development, function, and behavioral responses. To further characterize the genetic influences in alcoholism and the effects of alcohol consumption on gene expression, we used a highly sensitive exon microarray to examine mRNA expression in human frontal cortex of alcoholics and control males. Messenger RNA was isolated from the dorsolateral prefrontal cortex (dlPFC; Brodmann area 9) of 7 adult alcoholic (6 males, 1 female, mean age 49 years) and 7 matched controls. Affymetrix Human Exon 1.0 ST array was performed according to standard procedures and the results analyzed at the gene level. Microarray findings were validated using quantitative reverse transcription polymerase chain reaction, and the ontology of disturbed genes characterized using Ingenuity Pathway Analysis (IPA). Decreased mRNA expression was observed for genes involved in cellular adhesion (e.g., CTNNA3, ITGA2), transport (e.g., TF, ABCA8), nervous system development (e.g., LRP2, UGT8, GLDN), and signaling (e.g., RASGRP3, LGR5) with influence over lipid and myelin synthesis (e.g., ASPA, ENPP2, KLK6). IPA identified disturbances in network functions associated with neurological disease and development including cellular assembly and organization impacting on psychological disorders. Our data in alcoholism support a reduction in expression of dlPFC mRNA for genes involved with neuronal growth, differentiation, and signaling that targets white matter of the brain. Copyright © 2014 by the Research Society on Alcoholism.

Brain network disturbance related to posttraumatic stress and traumatic brain injury in veterans.

PubMed

Spielberg, Jeffrey M; McGlinchey, Regina E; Milberg, William P; Salat, David H

2015-08-01

Understanding the neural causes and consequences of posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) is a high research priority, given the high rates of associated disability and suicide. Despite remarkable progress in elucidating the brain mechanisms of PTSD and mTBI, a comprehensive understanding of these conditions at the level of brain networks has yet to be achieved. The present study sought to identify functional brain networks and topological properties (measures of network organization and function) related to current PTSD severity and mTBI. Graph theoretic tools were used to analyze resting-state functional magnetic resonance imaging data from 208 veterans of Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn, all of whom had experienced a traumatic event qualifying for PTSD criterion A. Analyses identified brain networks and topological network properties linked to current PTSD symptom severity, mTBI, and the interaction between PTSD and mTBI. Two brain networks were identified in which weaker connectivity was linked to higher PTSD re-experiencing symptoms, one of which was present only in veterans with comorbid mTBI. Re-experiencing was also linked to worse functional segregation (necessary for specialized processing) and diminished influence of key regions on the network, including the hippocampus. Findings of this study demonstrate that PTSD re-experiencing symptoms are linked to weakened connectivity in a network involved in providing contextual information. A similar relationship was found in a separate network typically engaged in the gating of working memory, but only in veterans with mTBI. Published by Elsevier Inc.

A re-examination of neural basis of language processing: proposal of a dynamic hodotopical model from data provided by brain stimulation mapping during picture naming.

PubMed

Duffau, Hugues; Moritz-Gasser, Sylvie; Mandonnet, Emmanuel

2014-04-01

From recent findings provided by brain stimulation mapping during picture naming, we re-examine the neural basis of language. We studied structural-functional relationships by correlating the types of language disturbances generated by stimulation in awake patients, mimicking a transient virtual lesion both at cortical and subcortical levels (white matter and deep grey nuclei), with the anatomical location of the stimulation probe. We propose a hodotopical (delocalized) and dynamic model of language processing, which challenges the traditional modular and serial view. According to this model, following the visual input, the language network is organized in parallel, segregated (even if interconnected) large-scale cortico-subcortical sub-networks underlying semantic, phonological and syntactic processing. Our model offers several advantages (i) it explains double dissociations during stimulation (comprehension versus naming disorders, semantic versus phonemic paraphasias, syntactic versus naming disturbances, plurimodal judgment versus naming disorders); (ii) it takes into account the cortical and subcortical anatomic constraints; (iii) it explains the possible recovery of aphasia following a lesion within the "classical" language areas; (iv) it establishes links with a model executive functions. Copyright © 2013 Elsevier Inc. All rights reserved.

[Clinical-neuropsychological study of patients with hematomas, cavernomas and arteriovenous malformations of the brain stem].

PubMed

Buklina, S B; Gavriushin, A V; Okishev, D N

2009-01-01

A clinical-neuropsychological study of 25 patients with hematomas, cavernomas and arteriovenous malformations of different brain stem regions has been performed. Patients with hydrocephalic-hypertensive and dislocation syndromes as well as a history of neurological diseases were excluded from the study. All patients had hemorrhages in different brain stem regions, most of which had occurred several weeks ago. Hematomas were located in different regions of the pons (14 patients) and midbrain (7 patients) and spread to both regions in 4 patients. All patients underwent MRI study of the brain and complex neuropsychological investigation using the A.R. Luria's method. Neuropsychological symptoms before the surgery were found in 20 patients. Cognitive disturbances similar by the lesion of frontal lobes, in particular the promoter zone, that manifested themselves in disturbances of dynamic praxis, writing, verbal memory, were observed most often. Cognitive disturbances similar by the lesion of occipital hemisphere regions, i.e. disturbances of visual gnosis and spatial defects, were found less often. The most severe symptoms were observed in the lesion of the midbrain and upper regions of the pons.

[Disorders of higher mental functions in the early stages of hydrocephalus].

PubMed

Simernitskaia, E G; Simernitskiĭ, B P

1981-01-01

The authors have carried out neuropsychological examinations of 32 children operated for hydrocephalus on the first year of the life. A syndrome of the higher psychic function disturbances characteristics for children with early hydrocephalus is described, and the results of the neuropsychological function examinations were compared with the character, etiology, and gravity of the hydrocephalus. In the children with the early hydrocephalus a high incidence of sinistrality was revealed, the fact, that gives one grounds to explain the peculiarities of the syndrome observed in them by an anomaly of the development of the brain functional asymmetry.

Information flow between interacting human brains: Identification, validation, and relationship to social expertise.

PubMed

Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas

2015-04-21

Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender's and receiver's temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions.

[Metronidazole-Induced Encephalopathy during Brain Abscess Treatment:Two Case Reports].

PubMed

Yokoyama, Yuka; Asaoka, Katsuyuki; Sugiyama, Taku; Uchida, Kazuki; Shimbo, Daisuke; Kobayashi, Satoshi; Itamoto, Koji

2015-10-01

Metronidazole is a widely used antibiotic against anaerobic bacteria and protozoa. We report two cases of metronidazole-induced encephalopathy(MIE)during treatment of a brain abscess with metronidazole. The patients developed mental disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case 1: A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We initiated treatment with oral metronidazole. After taking the medication, she developed mental disturbance, and her brain MRI showed a hyperintensity within the corpus callosum. We suspected metronidazole toxicity and discontinued metronidazole treatment. The symptoms resolved rapidly within a week, and the hyperintensity on the MRI disappeared. Case 2: A 22-year-old man was admitted to our hospital with a brain abscess. We initiated treatment with oral metronidazole. On day 38, he developed mental disturbance, and his MRI showed hyperintensities within the bilateral dentate nuclei and corpus callosum. These symptoms were consistent with MIE. After cessation of metronidazole, his symptoms and abnormal MRI signals completely disappeared.

Correlation between language function and the left arcuate fasciculus detected by diffusion tensor imaging tractography after brain tumor surgery.

PubMed

Hayashi, Yutaka; Kinoshita, Masashi; Nakada, Mitsutoshi; Hamada, Jun-ichiro

2012-11-01

Disturbance of the arcuate fasciculus in the dominant hemisphere is thought to be associated with language-processing disorders, including conduction aphasia. Although the arcuate fasciculus can be visualized in vivo with diffusion tensor imaging (DTI) tractography, its involvement in functional processes associated with language has not been shown dynamically using DTI tractography. In the present study, to clarify the participation of the arcuate fasciculus in language functions, postoperative changes in the arcuate fasciculus detected by DTI tractography were evaluated chronologically in relation to postoperative changes in language function after brain tumor surgery. Preoperative and postoperative arcuate fasciculus area and language function were examined in 7 right-handed patients with a brain tumor in the left hemisphere located in proximity to part of the arcuate fasciculus. The arcuate fasciculus was depicted, and its area was calculated using DTI tractography. Language functions were measured using the Western Aphasia Battery (WAB). After tumor resection, visualization of the arcuate fasciculus was increased in 5 of the 7 patients, and the total WAB score improved in 6 of the 7 patients. The relative ratio of postoperative visualized area of the arcuate fasciculus to preoperative visualized area of the arcuate fasciculus was increased in association with an improvement in postoperative language function (p = 0.0039). The role of the left arcuate fasciculus in language functions can be evaluated chronologically in vivo by DTI tractography after brain tumor surgery. Because increased postoperative visualization of the fasciculus was significantly associated with postoperative improvement in language functions, the arcuate fasciculus may play an important role in language function, as previously thought. In addition, postoperative changes in the arcuate fasciculus detected by DTI tractography could represent a predicting factor for postoperative language-dependent functional outcomes in patients with brain tumor.

Intracellular pH regulation by acid-base transporters in mammalian neurons

PubMed Central

Ruffin, Vernon A.; Salameh, Ahlam I.; Boron, Walter F.; Parker, Mark D.

2014-01-01

Intracellular pH (pHi) regulation in the brain is important in both physiological and physiopathological conditions because changes in pHi generally result in altered neuronal excitability. In this review, we will cover 4 major areas: (1) The effect of pHi on cellular processes in the brain, including channel activity and neuronal excitability. (2) pHi homeostasis and how it is determined by the balance between rates of acid loading (JL) and extrusion (JE). The balance between JE and JL determine steady-state pHi, as well as the ability of the cell to defend pHi in the face of extracellular acid-base disturbances (e.g., metabolic acidosis). (3) The properties and importance of members of the SLC4 and SLC9 families of acid-base transporters expressed in the brain that contribute to JL (namely the Cl-HCO3 exchanger AE3) and JE (the Na-H exchangers NHE1, NHE3, and NHE5 as well as the Na+- coupled HCO3− transporters NBCe1, NBCn1, NDCBE, and NBCn2). (4) The effect of acid-base disturbances on neuronal function and the roles of acid-base transporters in defending neuronal pHi under physiopathologic conditions. PMID:24592239

Pattern classification of brain activation during emotional processing in subclinical depression: psychosis proneness as potential confounding factor.

PubMed

Modinos, Gemma; Mechelli, Andrea; Pettersson-Yeo, William; Allen, Paul; McGuire, Philip; Aleman, Andre

2013-01-01

We used Support Vector Machine (SVM) to perform multivariate pattern classification based on brain activation during emotional processing in healthy participants with subclinical depressive symptoms. Six-hundred undergraduate students completed the Beck Depression Inventory II (BDI-II). Two groups were subsequently formed: (i) subclinical (mild) mood disturbance (n = 17) and (ii) no mood disturbance (n = 17). Participants also completed a self-report questionnaire on subclinical psychotic symptoms, the Community Assessment of Psychic Experiences Questionnaire (CAPE) positive subscale. The functional magnetic resonance imaging (fMRI) paradigm entailed passive viewing of negative emotional and neutral scenes. The pattern of brain activity during emotional processing allowed correct group classification with an overall accuracy of 77% (p = 0.002), within a network of regions including the amygdala, insula, anterior cingulate cortex and medial prefrontal cortex. However, further analysis suggested that the classification accuracy could also be explained by subclinical psychotic symptom scores (correlation with SVM weights r = 0.459, p = 0.006). Psychosis proneness may thus be a confounding factor for neuroimaging studies in subclinical depression.

How does the motor relearning program improve neurological function of brain ischemia monkeys?☆

PubMed Central

Yin, Yong; Gu, Zhen; Pan, Lei; Gan, Lu; Qin, Dongdong; Yang, Bo; Guo, Jin; Hu, Xintian; Wang, Tinghua; Feng, Zhongtang

2013-01-01

The motor relearning program can significantly improve various functional disturbance induced by ischemic cerebrovascular diseases. However, its mechanism of action remains poorly understood. In injured brain tissues, glial fibrillary acidic protein and neurofilament protein changes can reflect the condition of injured neurons and astrocytes, while vascular endothelial growth factor and basic fibroblast growth factor changes can indicate angiogenesis. In the present study, we induced ischemic brain injury in the rhesus macaque by electrocoagulation of the M1 segment of the right middle cerebral artery. The motor relearning program was conducted for 60 days from the third day after model establishment. Immunohistochemistry and single-photon emission CT showed that the numbers of glial fibrillary acidic protein-, neurofilament protein-, vascular endothelial growth factor- and basic fibroblast growth factor-positive cells were significantly increased in the infarcted side compared with the contralateral hemisphere following the motor relearning program. Moreover, cerebral blood flow in the infarcted side was significantly improved. The clinical rating scale for stroke was used to assess neurological function changes in the rhesus macaque following the motor relearning program. Results showed that motor function was improved, and problems with consciousness, self-care ability and balance function were significantly ameliorated. These findings indicate that the motor relearning program significantly promoted neuronal regeneration, repair and angiogenesis in the surroundings of the infarcted hemisphere, and improve neurological function in the rhesus macaque following brain ischemia. PMID:25206440

Assessment of brain activity during voluntary anal sphincter contraction: Comparative study in women with and without fecal incontinence.

PubMed

Parés, D; Martínez-Vilalta, M; Ortiz, H; Soriano-Mas, C; Maestre-Gonzalez, Y; Pujol, J; Grande, L

2018-04-14

Voluntary anal sphincter function is driven by an extended network of brain structures, most of which are still unknown. Disturbances in this function may cause fecal incontinence. The aim of this study was to characterize the cerebral areas involved in voluntary contraction of the anorectal sphincter in healthy women and in a group of patients with fecal incontinence by using a standardized functional magnetic resonance imaging (fMRI) protocol. This comparative study included 12 healthy women (mean age 53.17 ± 4.93 years) and 12 women with fecal incontinence (56.25 ± 6.94 years). An MRI-compatible anal manometer was used to register voluntary external anal sphincter contraction. During brain fMRI imaging, participants were cued to perform 10-s series of self-paced anal sphincter contractions at an approximate rate of 1 Hz. Brain structures linked to anal sphincter contractions were mapped and the findings were compared between the 2 study groups. There were no differences in the evoked brain activity between the 2 groups. In healthy women, group fMRI analysis revealed significant activations in medial primary motor cortices, supplementary motor area, bilateral putamen, and cerebellum, as well as in the supramarginal gyrus and visual areas. In patients with fecal incontinence, the activation pattern involved similar regions without significant differences with healthy women. This brain fMRI-anorectal protocol was able to map the brain regions linked to voluntary anal sphincter function in healthy and women with fecal incontinence. © 2018 John Wiley & Sons Ltd.

The neurobiology of addiction: the perspective from magnetic resonance imaging present and future

PubMed Central

Nestor, Liam J.

2016-01-01

Abstract Background and Aims Addiction is associated with severe economic and social consequences and personal tragedies, the scientific exploration of which draws upon investigations at the molecular, cellular and systems levels with a wide variety of technologies. Magnetic resonance imaging (MRI) has been key to mapping effects observed at the microscopic and mesoscopic scales. The range of measurements from this apparatus has opened new avenues linking neurobiology to behaviour. This review considers the role of MRI in addiction research, and what future technological improvements might offer. Methods A hermeneutic strategy supplemented by an expansive, systematic search of PubMed, Scopus and Web of Science databases, covering from database inception to October 2015, with a conjunction of search terms relevant to addiction and MRI. Formal meta‐analyses were prioritized. Results Results from methods that probe brain structure and function suggest frontostriatal circuitry disturbances within specific cognitive domains, some of which predict drug relapse and treatment response. New methods of processing imaging data are opening opportunities for understanding the role of cerebral vasculature, a global view of brain communication and the complex topology of the cortical surface and drug action. Future technological advances include increases in MRI field strength, with concomitant improvements in image quality. Conclusions The magnetic resonance imaging literature provides a limited but convergent picture of the neurobiology of addiction as global changes to brain structure and functional disturbances to frontostriatal circuitry, accompanied by changes in anterior white matter. PMID:27452960

[Memory and brain--neurobiological correlates of memory disturbances].

PubMed

Calabrese, P; Markowitsch, H J

2003-04-01

A differentiation of memory is possible on the basis of chronological and contents-related aspects. Furthermore, it is possible to make process-specific subdivisions (encoding, transfer, consolidation, retrieval). The time-related division on the one hand refers to the general differentiation into short-term and long-term memory, and, on the other, to that between anterograde and retrograde memory ("new" and "old memory"; measured from a given time point, usually that when brain damage occurred). Anterograde memory means the successful encoding and storing of new information; retrograde the ability to retrieve successfully acquired and/or stored information. On the contents-based level, memory can be divided into five basic long-term systems--episodic memory, the knowledge system, perceptual, procedural and the priming form of memory. Neural correlates for these divisions are discussed with special emphasis of the episodic and the knowledge systems, based both on normal individuals and brain-damaged subjects. It is argued that structures of the limbic system are important for encoding of information and for its transfer into long-term memory. For this, two independent, but interacting memory circuits are proposed--one of them controlling and integrating primarily the emotional, and the other primarily the cognitive components of newly incoming information. For information storage principally neocortical structures are regarded as important and for the recall of information from the episodic and semantic memory systems the combined action of portions of prefrontal and anterior temporal regions is regarded as essential. Within this fronto-temporal agglomerate, a moderate hemispheric-specificity is assumed to exist with the right-hemispheric combination being mainly engaged in episodic memory retrieval and the left-hemispheric in that of semantic information. Evidence for this specialization comes from the results from focally brain-damaged patients as well as from that functional brain imaging in normal human subjects. Comparing results from imaging studies in memory disturbed patients with brain damage and from patients with a psychiatric diagnosis (e. g., psychogenic amnesia) revealed that both patient groups demonstrate comparable metabolic changes on the brain level. It can therefore be concluded that in neurological patients distinct, identifiable tissue damage is existent, while in psychiatric patients changes in the brain's biochemistry (release of stress hormones, and transmitters) constitute the physiological bases for the memory disturbances.

Probabilistic diffusion tractography and graph theory analysis reveal abnormal white matter structural connectivity networks in drug-naive boys with attention deficit/hyperactivity disorder.

PubMed

Cao, Qingjiu; Shu, Ni; An, Li; Wang, Peng; Sun, Li; Xia, Ming-Rui; Wang, Jin-Hui; Gong, Gao-Lang; Zang, Yu-Feng; Wang, Yu-Feng; He, Yong

2013-06-26

Attention-deficit/hyperactivity disorder (ADHD), which is characterized by core symptoms of inattention and hyperactivity/impulsivity, is one of the most common neurodevelopmental disorders of childhood. Neuroimaging studies have suggested that these behavioral disturbances are associated with abnormal functional connectivity among brain regions. However, the alterations in the structural connections that underlie these behavioral and functional deficits remain poorly understood. Here, we used diffusion magnetic resonance imaging and probabilistic tractography method to examine whole-brain white matter (WM) structural connectivity in 30 drug-naive boys with ADHD and 30 healthy controls. The WM networks of the human brain were constructed by estimating inter-regional connectivity probability. The topological properties of the resultant networks (e.g., small-world and network efficiency) were then analyzed using graph theoretical approaches. Nonparametric permutation tests were applied for between-group comparisons of these graphic metrics. We found that both the ADHD and control groups showed an efficient small-world organization in the whole-brain WM networks, suggesting a balance between structurally segregated and integrated connectivity patterns. However, relative to controls, patients with ADHD exhibited decreased global efficiency and increased shortest path length, with the most pronounced efficiency decreases in the left parietal, frontal, and occipital cortices. Intriguingly, the ADHD group showed decreased structural connectivity in the prefrontal-dominant circuitry and increased connectivity in the orbitofrontal-striatal circuitry, and these changes significantly correlated with the inattention and hyperactivity/impulsivity symptoms, respectively. The present study shows disrupted topological organization of large-scale WM networks in ADHD, extending our understanding of how structural disruptions of neuronal circuits underlie behavioral disturbances in patients with ADHD.

Sex-Specific Patterns of Aberrant Brain Function in First-Episode Treatment-Naive Patients with Schizophrenia.

PubMed

Lei, Wei; Li, Mingli; Deng, Wei; Zhou, Yi; Ma, Xiaohong; Wang, Qiang; Guo, Wanjun; Li, Yinfei; Jiang, Lijun; Han, Yuanyuan; Huang, Chaohua; Hu, Xun; Li, Tao

2015-07-16

Male and female patients with schizophrenia show significant differences in a number of important clinical features, yet the neural substrates of these differences are still poorly understood. Here we explored the sex differences in the brain functional aberrations in 124 treatment-naïve patients with first-episode schizophrenia (61 males), compared with 102 age-matched healthy controls (50 males). Maps of degree centrality (DC) and amplitude of low-frequency fluctuations (ALFF) were constructed using resting-state functional magnetic resonance imaging data and compared between groups. We found that: (1) Selective DC reduction was observed in the right putamen (Put_R) in male patients and the left middle frontal gyrus (MFG) in female patients; (2) Functional connectivity analysis (using Put_R and MFG as seeds) found that male and female patients have disturbed functional integration in two separate networks, i.e., the sensorimotor network and the default mode network; (3) Significant ALFF alterations were also observed in these two networks in both genders; (4) Sex specific brain functional alterations were associated with various symptoms in patients. These results suggested that sex-specific patterns of functional aberration existed in schizophrenia, and these patterns were associated with the clinical features both in male and female patients.

Effects of ellagic acid pretreatment on renal functions disturbances induced by global cerebral ischemic-reperfusion in rat.

PubMed

Nejad, Khojasteh Hoseiny; Gharib-Naseri, Mohammad Kazem; Sarkaki, Alireza; Dianat, Mahin; Badavi, Mohammad; Farbood, Yaghoub

2017-01-01

Global cerebral ischemia-reperfusion (GCIR) causes disturbances in brain functions as well as other organs such as kidney. Our aim was to evaluate the protective effects of ellagic acid (EA) on certain renal disfunction after GCIR. Adult male Wistar rats (n=32, 250-300 g) were used. GCIR was induced by bilateral vertebral and common carotid arteries occlusion (4-VO). Animal groups were: 1) received DMSO/saline (10%) as solvent of EA, 2) solvent + GCIR, 3) EA + GCIR, and 4) EA. Under anesthesia with ketamine/xylazine, GCIR was induced (20 and 30 min respectively) in related groups. EA (100 mg/kg, dissolved in DMSO/saline (10%) or solvent was administered (1.5 ml/kg) orally for 10 consecutive days to the related groups. EEG was recorded from NTS in GCIR treated groups. Our data showed that: a) EEG in GCIR treated groups was flattened. b) GCIR reduced GFR ( P <0.01) and pretreatment with EA attenuated this reduction. c) BUN was increased by GCIR ( P <0.001) and pretreatment with EA improved the BUN to normal level. d) Serum creatinine concentration was elevated by GCIR but not significantly, however, in EA+GCIR group serum creatinine was reduced ( P <0.05). e) GCIR induced proteinuria ( P <0.05) but, EA was unable to reduced proteinuria. Results indicate that GCIR impairs certain renal functions and EA as an antioxidant can improve these functions. Our results suggest the possible usefulness of ellagic acid in patients with brain stroke.

Scents and Nonsense: Olfactory Dysfunction in Schizophrenia

PubMed Central

Turetsky, Bruce I.; Hahn, Chang-Gyu; Borgmann-Winter, Karin; Moberg, Paul J.

2009-01-01

Among the sensory modalities, olfaction is most closely associated with the frontal and temporal brain regions that are implicated in schizophrenia and most intimately related to the affective and mnemonic functions that these regions subserve. Olfactory probes may therefore be ideal tools through which to assess the structural and functional integrity of the neural substrates that underlie disease-related cognitive and emotional disturbances. Perhaps more importantly, to the extent that early sensory afferents are also disrupted in schizophrenia, the olfactory system—owing to its strategic anatomic location—may be especially vulnerable to such disruption. Olfactory dysfunction may therefore be a sensitive indicator of schizophrenia pathology and may even serve as an “early warning” sign of disease vulnerability or onset. In this article, we review the evidence supporting a primary olfactory sensory disturbance in schizophrenia. Convergent data indicate that structural and functional abnormalities extend from the cortex to the most peripheral elements of the olfactory system. These reflect, in part, a genetically mediated neurodevelopmental etiology. Gross structural and functional anomalies are mirrored by cellular and molecular abnormalities that suggest decreased or faulty innervation and/or dysregulation of intracellular signaling. A unifying mechanistic hypothesis may be the epigenetic regulation of gene expression. With the opportunity to obtain olfactory neural tissue from live patients through nasal epithelial biopsy, the peripheral olfactory system offers a uniquely accessible window through which the pathophysiological antecedents and sequelae of schizophrenia may be observed. This could help to clarify underlying brain mechanisms and facilitate identification of clinically relevant biomarkers. PMID:19793796

Cerebral Glucose Metabolism and Sedation in Brain-injured Patients: A Microdialysis Study.

PubMed

Hertle, Daniel N; Santos, Edgar; Hagenston, Anna M; Jungk, Christine; Haux, Daniel; Unterberg, Andreas W; Sakowitz, Oliver W

2015-07-01

Disturbed brain metabolism is a signature of primary damage and/or precipitates secondary injury processes after severe brain injury. Sedatives and analgesics target electrophysiological functioning and are as such well-known modulators of brain energy metabolism. Still unclear, however, is how sedatives impact glucose metabolism and whether they differentially influence brain metabolism in normally active, healthy brain and critically impaired, injured brain. We therefore examined and compared the effects of anesthetic drugs under both critical (<1 mmol/L) and noncritical (>1 mmol/L) extracellular brain glucose levels. We performed an explorative, retrospective analysis of anesthetic drug administration and brain glucose concentrations, obtained by bedside microdialysis, in 19 brain-injured patients. Our investigations revealed an inverse linear correlation between brain glucose and both the concentration of extracellular glutamate (Pearson r=-0.58, P=0.01) and the lactate/glucose ratio (Pearson r=-0.55, P=0.01). For noncritical brain glucose levels, we observed a positive linear correlation between midazolam dose and brain glucose (P<0.05). For critical brain glucose levels, extracellular brain glucose was unaffected by any type of sedative. These findings suggest that the use of anesthetic drugs may be of limited value in attempts to influence brain glucose metabolism in injured brain tissue.

ENDOCRINE DISRUPTORS AS A THREAT TO NEUROLOGICAL FUNCTION

PubMed Central

Weiss, Bernard

2011-01-01

Endocrine disruption is a concept and principle whose origins can be traced to the beginnings of the environmental movement in the 1960s. It began with puzzlement about and the flaring of research on the decline of wildlife, particularly avian species. The proposed causes accented pesticides, especially persistent organochlorines such as DDT. Its scope gradually widened beyond pesticides, and, as endocrine disruption offered an explanation for the wildlife phenomena, it seemed to explain, as well, changes in fertility and disorders of male reproduction such as testicular cancer. Once disturbed gonadal hormone function became the most likely explanation, it provoked other questions. The most challenging arose because of how critical gonadal hormones are to brain function, especially as determinants of brain sexual differentiation. Pursuit of such connections has generated a robust literature embracing a broad swath of chemical classes. How endocrine disrupting chemicals influence the adult and aging brain is a question, so far mostly ignored because of the emphasis on early development, that warrants vigorous investigation. Gonadal hormones are crucial to optimal brain function during maturity and even senescence. They are pivotal to the processes of neurogenesis. They exert protective actions against neurodegenerative disorders such as dementia and support smoothly functioning cognitive activities. The limited research conducted so far on endocrine disruptors, aging, and neurogenesis argues that they should be overlooked no longer. PMID:21474148

Effect of Panpal pretreatment and antidotal treatment (HI-6 plus benactyzine) on respiratory and circulatory function in soman-poisoned rats.

PubMed

Kassa, J; Fusek, J

1997-10-01

1 The effect of pharmacological pretreatment (pyridostigmine, benactyzine and trihexyphenidyle), designated Panpal, and antidotal treatment (the oxime HI-6 plus benactyzine) in soman poisoning was investigated in a rat model with on-line monitoring of respiratory and circulatory parameters. 2 Soman poisoning caused a high decrease in respiratory rate as well as minute respiratory volume and an increase in mean arterial pressure from 30-120 min following soman challenge. Soman at sublethal dose also significantly inhibited acetylcholinesterase activity in diaphragm and various brain parts. 3 Panpal pretreatment as well as antidotal treatment were effective in improving the respiratory and circulatory function disturbed by soman without the ability to increase significantly soman-inhibited acetylcholinesterase activity in all brain parts studied. 4 The efficacy of combined Panpal pretreatment and antidotal treatment against sublethal soman poisoning was not different from the efficacy of Panpal pretreatment or antidotal treatment alone. 5 The results of this investigation suggest that Panpal pretreatment as well as antidotal treatment are able to restore respiratory and circulatory function in soman-poisoned rats without significant reactivation of brain acetylcholinesterase.

Resting-state theta band connectivity and graph analysis in generalized social anxiety disorder.

PubMed

Xing, Mengqi; Tadayonnejad, Reza; MacNamara, Annmarie; Ajilore, Olusola; DiGangi, Julia; Phan, K Luan; Leow, Alex; Klumpp, Heide

2017-01-01

Functional magnetic resonance imaging (fMRI) resting-state studies show generalized social anxiety disorder (gSAD) is associated with disturbances in networks involved in emotion regulation, emotion processing, and perceptual functions, suggesting a network framework is integral to elucidating the pathophysiology of gSAD. However, fMRI does not measure the fast dynamic interconnections of functional networks. Therefore, we examined whole-brain functional connectomics with electroencephalogram (EEG) during resting-state. Resting-state EEG data was recorded for 32 patients with gSAD and 32 demographically-matched healthy controls (HC). Sensor-level connectivity analysis was applied on EEG data by using Weighted Phase Lag Index (WPLI) and graph analysis based on WPLI was used to determine clustering coefficient and characteristic path length to estimate local integration and global segregation of networks. WPLI results showed increased oscillatory midline coherence in the theta frequency band indicating higher connectivity in the gSAD relative to HC group during rest. Additionally, WPLI values positively correlated with state anxiety levels within the gSAD group but not the HC group. Our graph theory based connectomics analysis demonstrated increased clustering coefficient and decreased characteristic path length in theta-based whole brain functional organization in subjects with gSAD compared to HC. Theta-dependent interconnectivity was associated with state anxiety in gSAD and an increase in information processing efficiency in gSAD (compared to controls). Results may represent enhanced baseline self-focused attention, which is consistent with cognitive models of gSAD and fMRI studies implicating emotion dysregulation and disturbances in task negative networks (e.g., default mode network) in gSAD.

Addressing neuropsychiatric disturbances during rehabilitation after traumatic brain injury: current and future methods

PubMed Central

Arciniegas, David B.

2011-01-01

Cognitive, emotional, behavioral, and sensorimotor disturbances are the principal clinical manifestations of traumatic brain injury (TBI) throughout the early postinjury period. These post-traumatic neuropsychiatric disturbances present substantial challenges to patients, their families, and clinicians providing their rehabilitative care, the optimal approaches to which remain incompletely developed. In this article, a neuropsychiairically informed, neurobiologically anchored approach to understanding and meeting challenges is described. The foundation for thai approach is laid, with a review of clinical case definitions of TBI and clarification of their intended referents. The differential diagnosis of event-related neuropsychiatric disturbances is considered next, after which the clinical and neurobiological heterogeneity within the diagnostic category of TBI are discussed. The clinical manifestations of biomechanical force-induced brain dysfunction are described as a state of post-traumatic encephalopathy (PTE) comprising several phenomenologically distinct stages, PTE is then used as a framework for understanding and clinically evaluating the neuropsychiatric sequelae of TBI encountered commonly during the early post-injury rehabilitation period, and for considering the types and timings of neurorehabilitative interventions. Finally, directions for future research that may address productively the challenges to TBI rehabilitation presented by neuropsychiatric disturbances are considered. PMID:22034400

The International Research Training Group on "Brain-Behavior Relationship of Normal and Disturbed Emotions in Schizophrenia and Autism" as an Example of German-American Cooperation in Doctoral Training

ERIC Educational Resources Information Center

Schneider, Frank; Gur, Ruben C.

2008-01-01

The International Research Training Group "Brain-Behavior Relationship of Normal and Disturbed Emotions in Schizophrenia and Autism" (IRTG 1328), funded by the German Research Council (DFG), is a German-American cooperation. Its major aims are interdisciplinary and international scientific cooperation and the support of young scientists…

Infantile cobalamin deficiency with cerebral lactate accumulation and sustained choline depletion.

PubMed

Horstmann, M; Neumaier-Probst, E; Lukacs, Z; Steinfeld, R; Ullrich, K; Kohlschütter, A

2003-06-01

A remarkable, intermittent sudden-onset vigilance and movement disorder in an exclusively breast-fed infant is reported, which was caused by cobalamin depletion due to maternal vitamin B12 malabsorption. The lack of cobalamin caused a severe encephalopathy in the infant, whose brain displayed a striking loss of volume and a delay of myelination. Proton magnetic resonance spectroscopy revealed an accumulation of lactate in the gray and white matter of the brain and a sustained depletion of choline-containing compounds in the white matter, reflecting a reversible disturbance of oxidative energy metabolism in brain cells and a long-lasting hypomyelination disorder. The clinical picture in conjunction with MRI and spectroscopic data of this case study yields more insight into the functions of cobalamin in the cerebral metabolism.

Topological Alterations of the Intrinsic Brain Network in Patients with Functional Dyspepsia.

PubMed

Nan, Jiaofen; Zhang, Li; Zhu, Fubao; Tian, Xiaorui; Zheng, Qian; Deneen, Karen M von; Liu, Jixin; Zhang, Ming

2016-01-31

Previous studies reported that integrated information in the brain ultimately determines the subjective experience of patients with chronic pain, but how the information is integrated in the brain connectome of functional dyspepsia (FD) patients remains largely unclear. The study aimed to quantify the topological changes of the brain network in FD patients. Small-world properties, network efficiency and nodal centrality were utilized to measure the changes in topological architecture in 25 FD patients and 25 healthy controls based on functional magnetic resonance imaging. Pearson's correlation assessed the relationship of each topological property with clinical symptoms. FD patients showed an increase of clustering coefficients and local efficiency relative to controls from the perspective of a whole network as well as elevated nodal centrality in the right orbital part of the inferior frontal gyrus, left anterior cingulate gyrus and left hippocampus, and decreased nodal centrality in the right posterior cingulate gyrus, left cuneus, right putamen, left middle occipital gyrus and right inferior occipital gyrus. Moreover, the centrality in the anterior cingulate gyrus was significantly associated with symptom severity and duration in FD patients. Nevertheless, the inclusion of anxiety and depression scores as covariates erased the group differences in nodal centralities in the orbital part of the inferior frontal gyrus and hippocampus. The results suggest topological disruption of the functional brain networks in FD patients, presumably in response to disturbances of sensory information integrated with emotion, memory, pain modulation, and selective attention in patients.

Not only in the brain: Cabanis and the Montpellierian tradition of localization.

PubMed

Kaitaro, T

2000-01-01

Antonio Damasio (1995) has recently presented evidence to the effect that we are perhaps wrong in thinking that it is only the brain that thinks. Rational decision making involves emotional reactions as a necessary condition and background. And since emotions involve bodily reactions which are not limited to the brain but which embrace the autonomous nervous system and the viscera, one could say that we actually think with our bodies and not merely with our brains. According to Damasio the incapacity of patients with frontal lobe pathology in decision making could be explained by a disturbance in emotional reactions involving the whole organism. Philosophical discussions concerning brains in a vat have completely forgotten these aspects of our mental life. Despite the fact that the idea that we think exclusively with our brains has during the modern age been a rather widely held "received view," there is a physiological and philosophical tradition which regarded mental functions as the result of the interaction of several organs, instead of seeing them as the result of the activity of the brain alone.

Mevalonolactone disrupts mitochondrial functions and induces permeability transition pore opening in rat brain mitochondria: Implications for the pathogenesis of mevalonic aciduria.

PubMed

Cecatto, Cristiane; Amaral, Alexandre Umpierrez; da Silva, Janaína Camacho; Wajner, Alessandro; Godoy, Kálita Dos Santos; Ribeiro, Rafael Teixeira; Gonçalves, Aline de Mello; Vargas, Carmen Regla; Wajner, Moacir

2017-09-01

Mevalonic aciduria (MVA) is caused by severe deficiency of mevalonic kinase activity leading to tissue accumulation and high urinary excretion of mevalonic acid (MA) and mevalonolactone (ML). Patients usually present severe neurologic symptoms whose pathophysiology is poorly known. Here, we tested the hypothesis that the major accumulating metabolites are toxic by investigating the in vitro effects of MA and ML on important mitochondrial functions in rat brain and liver mitochondria. ML, but not MA, markedly decreased mitochondrial membrane potential (ΔΨm), NAD(P)H content and the capacity to retain Ca 2+ in the brain, besides inducing mitochondrial swelling. These biochemical alterations were totally prevented by the classical inhibitors of mitochondrial permeability transition (MPT) cyclosporine A and ADP, as well as by ruthenium red in Ca 2+ -loaded mitochondria, indicating the involvement of MPT and an important role for mitochondrial Ca 2+ in these effects. ML also induced lipid peroxidation and markedly inhibited aconitase activity, an enzyme that is highly susceptible to free radical attack, in brain mitochondrial fractions, indicating that lipid and protein oxidative damage may underlie some of ML-induced deleterious effects including MTP induction. In contrast, ML and MA did not compromise oxidative phosphorylation in the brain and all mitochondrial functions evaluated in the liver, evidencing a selective toxicity of ML towards the central nervous system. Our present study provides for the first time evidence that ML impairs essential brain mitochondrial functions with the involvement of MPT pore opening. It is therefore presumed that disturbance of brain mitochondrial homeostasis possibly contributes to the neurologic symptoms in MVA. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Immune dysfunction and cognitive deficit in stress and physiological aging (Part I): Pathogenesis and risk factors].

PubMed

Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines without the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion of biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.

Disturbed temporal dynamics of brain synchronization in vision loss.

PubMed

Bola, Michał; Gall, Carolin; Sabel, Bernhard A

2015-06-01

Damage along the visual pathway prevents bottom-up visual input from reaching further processing stages and consequently leads to loss of vision. But perception is not a simple bottom-up process - rather it emerges from activity of widespread cortical networks which coordinate visual processing in space and time. Here we set out to study how vision loss affects activity of brain visual networks and how networks' activity is related to perception. Specifically, we focused on studying temporal patterns of brain activity. To this end, resting-state eyes-closed EEG was recorded from partially blind patients suffering from chronic retina and/or optic-nerve damage (n = 19) and healthy controls (n = 13). Amplitude (power) of oscillatory activity and phase locking value (PLV) were used as measures of local and distant synchronization, respectively. Synchronization time series were created for the low- (7-9 Hz) and high-alpha band (11-13 Hz) and analyzed with three measures of temporal patterns: (i) length of synchronized-/desynchronized-periods, (ii) Higuchi Fractal Dimension (HFD), and (iii) Detrended Fluctuation Analysis (DFA). We revealed that patients exhibit less complex, more random and noise-like temporal dynamics of high-alpha band activity. More random temporal patterns were associated with worse performance in static (r = -.54, p = .017) and kinetic perimetry (r = .47, p = .041). We conclude that disturbed temporal patterns of neural synchronization in vision loss patients indicate disrupted communication within brain visual networks caused by prolonged deafferentation. We propose that because the state of brain networks is essential for normal perception, impaired brain synchronization in patients with vision loss might aggravate the functional consequences of reduced visual input. Copyright © 2015 Elsevier Ltd. All rights reserved.

Abnormalities in emotion processing within cortical and subcortical regions in criminal psychopaths: evidence from a functional magnetic resonance imaging study using pictures with emotional content.

PubMed

Müller, Jürgen L; Sommer, Monika; Wagner, Verena; Lange, Kirsten; Taschler, Heidrun; Röder, Christian H; Schuierer, Gerhardt; Klein, Helmfried E; Hajak, Göran

2003-07-15

Neurobiology of psychopathy is important for our understanding of current neuropsychiatric questions. Despite a growing interest in biological research in psychopathy, its neural underpinning remains obscure. We used functional magnetic resonance imaging to study the influence of affective contents on brain activation in psychopaths. Series containing positive and negative pictures from the International Affective Picture System were shown to six male psychopaths and six male control subjects while 100 whole-brain echo-planar-imaging measurements were acquired. Differences in brain activation were evaluated using BrainVoyager software 4.6. In psychopaths, increased activation through negative contents was found right-sided in prefrontal regions and amygdala. Activation was reduced right-sided in the subgenual cingulate and the temporal gyrus, and left-sided in the dorsal cingulate and the parahippocampal gyrus. Increased activation through positive contents was found left-sided in the orbitofrontal regions. Activation was reduced in right medial frontal and medial temporal regions. These findings underline the hypotheses that psychopathy is neurobiologically reflected by dysregulation and disturbed functional connectivity of emotion-related brain regions. These findings may be interpreted within a framework including prefrontal regions that provide top-down control to and regulate bottom-up signals from limbic areas. Because of the small sample size, the results of this study have to be regarded as preliminary.

Altered spontaneous brain activity in patients with hemifacial spasm: a resting-state functional MRI study.

PubMed

Tu, Ye; Wei, Yongxu; Sun, Kun; Zhao, Weiguo; Yu, Buwei

2015-01-01

Resting-state functional magnetic resonance imaging (fMRI) has been used to detect the alterations of spontaneous neuronal activity in various neurological and neuropsychiatric diseases, but rarely in hemifacial spasm (HFS), a nervous system disorder. We used resting-state fMRI with regional homogeneity (ReHo) analysis to investigate changes in spontaneous brain activity of patients with HFS and to determine the relationship of these functional changes with clinical features. Thirty patients with HFS and 33 age-, sex-, and education-matched healthy controls were included in this study. Compared with controls, HFS patients had significantly decreased ReHo values in left middle frontal gyrus (MFG), left medial cingulate cortex (MCC), left lingual gyrus, right superior temporal gyrus (STG) and right precuneus; and increased ReHo values in left precentral gyrus, anterior cingulate cortex (ACC), right brainstem, and right cerebellum. Furthermore, the mean ReHo value in brainstem showed a positive correlation with the spasm severity (r = 0.404, p = 0.027), and the mean ReHo value in MFG was inversely related with spasm severity in HFS group (r = -0.398, p = 0.028). This study reveals that HFS is associated with abnormal spontaneous brain activity in brain regions most involved in motor control and blinking movement. The disturbances of spontaneous brain activity reflected by ReHo measurements may provide insights into the neurological pathophysiology of HFS.

Altered blood-brain barrier transport in neuro-inflammatory disorders.

PubMed

Schenk, Geert J; de Vries, Helga E

2016-06-01

During neurodegenerative and neuroinflammatory disorders of the central nervous system (CNS), such as Alzheimer's disease (AD) and multiple sclerosis (MS), the protective function of the blood-brain barrier (BBB) may be severely impaired. The general neuro-inflammatory response, ranging from activation of glial cells to immune cell infiltration that is frequently associated with such brain diseases may underlie the loss of the integrity and function of the BBB. Consequentially, the delivery and disposition of drugs to the brain will be altered and may influence the treatment efficiency of such diseases. Altered BBB transport of drugs into the CNS during diseases may be the result of changes in both specific transport and non-specific transport pathways. Potential alterations in transport routes like adsorptive mediated endocytosis and receptor-mediated endocytosis may affect drug delivery to the brain. As such, drugs that normally are unable to traverse the BBB may reach their target in the diseased brain due to increased permeability. In contrast, the delivery of (targeted) drugs could be hampered during inflammatory conditions due to disturbed transport mechanisms. Therefore, the inventory of the neuro-inflammatory status of the neurovasculature (or recovery thereof) is of utmost importance in choosing and designing an adequate drug targeting strategy under disease conditions. Within this review we will briefly discuss how the function of the BBB can be affected during disease and how this may influence the delivery of drugs into the diseased CNS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dysfunctions in brain networks supporting empathy: An fMRI study in adults with autism spectrum disorders

PubMed Central

Schulte-Rüther, Martin; Greimel, Ellen; Markowitsch, Hans J.; Kamp-Becker, Inge; Remschmidt, Helmut; Fink, Gereon R.; Piefke, Martina

2010-01-01

The present study aimed at identifying dysfunctions in brain networks that may underlie disturbed empathic behavior in autism spectrum disorders (ASD). During functional magnetic resonance imaging, subjects were asked to identify the emotional state observed in a facial stimulus (other-task) or to evaluate their own emotional response (self-task). Behaviorally, ASD subjects performed equally to the control group during the other-task, but showed less emotionally congruent responses in the self-task. Activations in brain regions related to theory of mind were observed in both groups. Activations of the medial prefrontal cortex (MPFC) were located in dorsal subregions in ASD subjects and in ventral areas in control subjects. During the self-task, ASD subjects activated an additional network of frontal and inferior temporal areas. Frontal areas previously associated with the human mirror system were activated in both tasks in control subjects, while ASD subjects recruited these areas during the self-task only. Activations in the ventral MPFC may provide the basis for one's “emotional bond” with other persons’ emotions. Such atypical patterns of activation may underlie disturbed empathy in individuals with ASD. Subjects with ASD may use an atypical cognitive strategy to gain access to their own emotional state in response to other people's emotions. PMID:20945256

The roles of cerebral blood flow, capillary transit time heterogeneity, and oxygen tension in brain oxygenation and metabolism

PubMed Central

Jespersen, Sune N; Østergaard, Leif

2012-01-01

Normal brain function depends critically on moment-to-moment regulation of oxygen supply by the bloodstream to meet changing metabolic needs. Neurovascular coupling, a range of mechanisms that converge on arterioles to adjust local cerebral blood flow (CBF), represents our current framework for understanding this regulation. We modeled the combined effects of CBF and capillary transit time heterogeneity (CTTH) on the maximum oxygen extraction fraction (OEFmax) and metabolic rate of oxygen that can biophysically be supported, for a given tissue oxygen tension. Red blood cell velocity recordings in rat brain support close hemodynamic–metabolic coupling by means of CBF and CTTH across a range of physiological conditions. The CTTH reduction improves tissue oxygenation by counteracting inherent reductions in OEFmax as CBF increases, and seemingly secures sufficient oxygenation during episodes of hyperemia resulting from cortical activation or hypoxemia. In hypoperfusion and states of blocked CBF, both lower oxygen tension and CTTH may secure tissue oxygenation. Our model predicts that disturbed capillary flows may cause a condition of malignant CTTH, in which states of higher CBF display lower oxygen availability. We propose that conditions with altered capillary morphology, such as amyloid, diabetic or hypertensive microangiopathy, and ischemia–reperfusion, may disturb CTTH and thereby flow-metabolism coupling and cerebral oxygen metabolism. PMID:22044867

Dynamic changes of Foxp3(+) regulatory T cells in spleen and brain of canine distemper virus-infected dogs.

PubMed

Qeska, V; Barthel, Y; Iseringhausen, M; Tipold, A; Stein, V M; Khan, M A; Baumgärtner, W; Beineke, A

2013-12-15

Canine distemper virus (CDV) infection causes immunosuppression and demyelinating leukoencephalitis in dogs. In viral diseases, an ambiguous function of regulatory T cells (Treg), with both beneficial effects by reducing immunopathology and detrimental effects by inhibiting antiviral immunity, has been described. However, the role of Treg in the pathogenesis of canine distemper remains unknown. In order to determine the effect of CDV upon immune homeostasis, the amount of Foxp3(+) Treg in spleen and brain of naturally infected dogs has been determined by immunohistochemistry. In addition, splenic cytokine expression has been quantified by reverse transcriptase polymerase chain reaction. Splenic depletion of Foxp3(+) Treg was associated with an increased mRNA-expression of tumor necrosis factor and decreased transcription of interleukin-2 in the acute disease phase, indicative of disturbed immunological counter regulation in peripheral lymphoid organs. In the brain, a lack of Foxp3(+) Treg in predemyelinating and early demyelinating lesions and significantly increased infiltrations of Foxp3(+) Treg in chronic demyelinating lesions were observed. In conclusion, disturbed peripheral and CNS immune regulation associated with a reduction of Treg represents a potential prerequisite for excessive neuroinflammation and early lesion development in canine distemper leukoencephalitis. © 2013 Elsevier B.V. All rights reserved.

Dysfunctions in brain networks supporting empathy: an fMRI study in adults with autism spectrum disorders.

PubMed

Schulte-Rüther, Martin; Greimel, Ellen; Markowitsch, Hans J; Kamp-Becker, Inge; Remschmidt, Helmut; Fink, Gereon R; Piefke, Martina

2011-01-01

The present study aimed at identifying dysfunctions in brain networks that may underlie disturbed empathic behavior in autism spectrum disorders (ASD). During functional magnetic resonance imaging, subjects were asked to identify the emotional state observed in a facial stimulus (other-task) or to evaluate their own emotional response (self-task). Behaviorally, ASD subjects performed equally to the control group during the other-task, but showed less emotionally congruent responses in the self-task. Activations in brain regions related to theory of mind were observed in both groups. Activations of the medial prefrontal cortex (MPFC) were located in dorsal subregions in ASD subjects and in ventral areas in control subjects. During the self-task, ASD subjects activated an additional network of frontal and inferior temporal areas. Frontal areas previously associated with the human mirror system were activated in both tasks in control subjects, while ASD subjects recruited these areas during the self-task only. Activations in the ventral MPFC may provide the basis for one's "emotional bond" with other persons' emotions. Such atypical patterns of activation may underlie disturbed empathy in individuals with ASD. Subjects with ASD may use an atypical cognitive strategy to gain access to their own emotional state in response to other people's emotions.

Neuroendocrine Disturbances One to Five or More Years after Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage: Data from the German Database on Hypopituitarism.

PubMed

Krewer, Carmen; Schneider, Manfred; Schneider, Harald Jörn; Kreitschmann-Andermahr, Ilonka; Buchfelder, Michael; Faust, Michael; Berg, Christian; Wallaschofski, Henri; Renner, Caroline; Uhl, Eberhard; Koenig, Eberhard; Jordan, Martina; Stalla, Günter Karl; Kopczak, Anna

2016-08-15

Neuroendocrine disturbances are common after traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH), but only a few data exist on long-term anterior pituitary deficiencies after brain injury. We present data from the Structured Data Assessment of Hypopituitarism after TBI and SAH, a multi-center study including 1242 patients. We studied a subgroup of 351 patients, who had sustained a TBI (245) or SAH (106) at least 1 year before endocrine assessment (range 1-55 years) in a separate analysis. The highest prevalence of neuroendocrine disorders was observed 1-2 years post-injury, and it decreased over time only to show another maximum in the long-term phase in patients with brain injury occurring ≥5 years prior to assessment. Gonadotropic and somatotropic insufficiencies were most common. In the subgroup from 1 to 2 years after brain injury (n = 126), gonadotropic insufficiency was the most common hormonal disturbance (19%, 12/63 men) followed by somatotropic insufficiency (11.5%, 7/61), corticotropic insufficiency (9.2%, 11/119), and thyrotropic insufficiency (3.3%, 4/122). In patients observed ≥ 5 years after brain injury, the prevalence of somatotropic insufficiency increased over time to 24.1%, whereas corticotropic and thyrotrophic insufficiency became less frequent (2.5% and 0%, respectively). The prevalence differed regarding the diagnostic criteria (laboratory values vs. physician`s diagnosis vs. stimulation tests). Our data showed that neuroendocrine disturbances are frequent even years after TBI or SAH, in a cohort of patients who are still on medical treatment.

[Anti-Ma2, anti-NMDA-receptor and anti-GluRε2 limbic encephalitis with testicular seminoma: short-term memory disturbance].

PubMed

Kubota, Akihiro; Tajima, Takashi; Narukawa, Shinya; Yamazato, Masamizu; Fukaura, Hikoaki; Takahashi, Yukitoshi; Tanaka, Keiko; Shimizu, Jun; Nomura, Kyoichi

2012-01-01

A 36-year-old man presented with cognitive impairment and disturbance of short-term memory functions with character change. Cerebrospinal fluid analysis revealed no abnormalities; however, brain MRI revealed high-signal intensity from bilateral hippocampus lesions on fluid attenuated inversion recovery (FLAIR) images and T(2) weighted images. The 18F-fluorodeoxyglucose PET demonstrated high glucose uptake in the bilateral hippocampus lesions. He was diagnosed as limbic encephalitis, and was administered high-dose intravenous methylprednisolone and immune adsorption plasma therapy followed by intravenous immunoglobulin therapy. MRI abnormalities improved after treatment but recent memory disturbance remained. Ma2 antibody, NMDA-receptor antibody, and GluRε2 antibody were positive. Eleven months atter the onset of disease, the tumor was identified in left testicle by ultrasound and removed the tumor. The pathological findings were seminoma. We experienced a case of paraneoplastic limbic encephalitis associated with seminoma with short-term memory disturbance. The occurrence of paraneoplastic limbic encephalitis with antibodies against cell membrane (NMDA-receptor antibody and GluRε2 antibody) and intracellular (Ma2 antibody) is rare even in the literature.

The cognitive cost of sleep lost

PubMed Central

McCoy, John G.; Strecker, Robert E.

2013-01-01

A substantial body of literature supports the intuitive notion that a good night’s sleep can facilitate human cognitive performance the next day. Deficits in attention, learning & memory, emotional reactivity, and higher-order cognitive processes, such as executive function and decision making, have all been documented following sleep disruption in humans. Thus, whilst numerous clinical and experimental studies link human sleep disturbance to cognitive deficits, attempts to develop valid and reliable rodent models of these phenomena are fewer, and relatively more recent. This review focuses primarily on the cognitive impairments produced by sleep disruption in rodent models of several human patterns of sleep loss/sleep disturbance. Though not an exclusive list, this review will focus on four specific types of sleep disturbance: total sleep deprivation, experimental sleep fragmentation, selective REM sleep deprivation, and chronic sleep restriction. The use of rodent models can provide greater opportunities to understand the neurobiological changes underlying sleep loss induced cognitive impairments. Thus, this review concludes with a description of recent neurobiological findings concerning the neuroplastic changes and putative brain mechanisms that may underlie the cognitive deficits produced by sleep disturbances. PMID:21875679

Information flow between interacting human brains: Identification, validation, and relationship to social expertise

PubMed Central

Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D.; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas

2015-01-01

Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender’s and receiver’s temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions. PMID:25848050

Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain.

PubMed

Abhilash, M; Alex, Manju; Mathews, Varghese V; Nair, R Harikumaran

2014-07-01

Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions. © The Author(s) 2014.

Altered expressions of apoptotic factors and synaptic markers in postmortem brain from bipolar disorder patients

PubMed Central

Kim, Hyung-Wook; Rapoport, Stanley I; Rao, Jagadeesh S

2009-01-01

Bipolar disorder (BD) is a progressive psychiatric disorder characterized by recurrent changes of mood, and is associated with cognitive decline. There is evidence of excitotoxicity, neuroinflammation, upregulated arachidonic acid (AA) cascade signaling and brain atrophy in BD patients. These observations suggest that BD pathology may be associated with apoptosis as well as with disturbed synaptic function. To test this hypothesis, we measured mRNA and protein levels of the pro-apoptotic (Bax, BAD, Caspase-9 and Caspase-3) and anti-apoptotic factors (BDNF and Bcl-2), and of pre- and post-synaptic markers (synaptophysin and drebrin), in postmortem brain from 10 BD patients and 10 age-matched controls. Consistent with the hypothesis, BD brains showed significant increases in protein and mRNA levels of the pro-apoptotic factors and significant decreases of levels of the anti-apoptotic factors and the synaptic markers, synaptophysin and drebrin. These differences may contribute to brain atrophy and progressive cognitive changes in BD. PMID:19945534

Self-other disturbance in borderline personality disorder: Neural, self-report, and performance-based evidence.

PubMed

Beeney, Joseph E; Hallquist, Michael N; Ellison, William D; Levy, Kenneth N

2016-01-01

Individuals with borderline personality disorder (BPD) display an impoverished sense of self and representations of self and others that shift between positive and negative poles. However, little research has investigated the nature of representational disturbance in BPD. The present study takes a multimodal approach. A card sort task was used to investigate complexity, integration, and valence of self-representation in BPD. Impairment in maintenance of self and other representations was assessed using a personality representational maintenance task. Finally, functional MRI (fMRI) was used to assess whether individuals with BPD show neural abnormalities related specifically to the self and what brain areas may be related to poor representational maintenance. Individuals with BPD sorted self-aspects suggesting more complexity of self-representation, but also less integration and more negative valence overall. On the representational maintenance task, individuals with BPD showed less consistency in their representations of self and others over the 3-hr period, but only for abstract, personality-based representations. Performance on this measure mediated between-groups brain activation in several areas supporting social cognition. We found no evidence for social-cognitive disturbance specific to the self. Additionally, the BPD group showed main effects, insensitive to condition, of hyperactivation in the medial prefrontal cortex, temporal parietal junction, several regions of the frontal pole, the precuneus and middle temporal gyrus, all areas crucial social cognition. In contrast, controls evidenced greater activation in visual, sensory, motor, and mirror neuron regions. These findings are discussed in relation to research regarding hypermentalization and the overlap between self- and other-disturbance. (c) 2016 APA, all rights reserved).

The role of sleep in regulating structural plasticity and synaptic strength: Implications for memory and cognitive function.

PubMed

Raven, Frank; Van der Zee, Eddy A; Meerlo, Peter; Havekes, Robbert

2018-06-01

Dendritic spines are the major sites of synaptic transmission in the central nervous system. Alterations in the strength of synaptic connections directly affect the neuronal communication, which is crucial for brain function as well as the processing and storage of information. Sleep and sleep loss bidirectionally alter structural plasticity, by affecting spine numbers and morphology, which ultimately can affect the functional output of the brain in terms of alertness, cognition, and mood. Experimental data from studies in rodents suggest that sleep deprivation may impact structural plasticity in different ways. One of the current views, referred to as the synaptic homeostasis hypothesis, suggests that wake promotes synaptic potentiation whereas sleep facilitates synaptic downscaling. On the other hand, several studies have now shown that sleep deprivation can reduce spine density and attenuate synaptic efficacy in the hippocampus. These data are the basis for the view that sleep promotes hippocampal structural plasticity critical for memory formation. Altogether, the impact of sleep and sleep loss may vary between regions of the brain. A better understanding of the role that sleep plays in regulating structural plasticity may ultimately lead to novel therapeutic approaches for brain disorders that are accompanied by sleep disturbances and sleep loss. Copyright © 2017 Elsevier Ltd. All rights reserved.

MEG connectivity analysis in patients with Alzheimer's disease using cross mutual information and spectral coherence.

PubMed

Alonso, Joan Francesc; Poza, Jesús; Mañanas, Miguel Angel; Romero, Sergio; Fernández, Alberto; Hornero, Roberto

2011-01-01

Alzheimer's disease (AD) is an irreversible brain disorder which represents the most common form of dementia in western countries. An early and accurate diagnosis of AD would enable to develop new strategies for managing the disease; however, nowadays there is no single test that can accurately predict the development of AD. In this sense, only a few studies have focused on the magnetoencephalographic (MEG) AD connectivity patterns. This study compares brain connectivity in terms of linear and nonlinear couplings by means of spectral coherence and cross mutual information function (CMIF), respectively. The variables defined from these functions provide statistically significant differences (p < 0.05) between AD patients and control subjects, especially the variables obtained from CMIF. The results suggest that AD is characterized by both decreases and increases of functional couplings in different frequency bands as well as by an increase in regularity, that is, more evident statistical deterministic relationships in AD patients' MEG connectivity. The significant differences obtained indicate that AD could disturb brain interactions causing abnormal brain connectivity and operation. Furthermore, the combination of coherence and CMIF features to perform a diagnostic test based on logistic regression improved the tests based on individual variables for its robustness.

Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future "Non-Cognitive" Outcomes of Alzheimer's Disease.

PubMed

Ingber, Adam P; Hassenstab, Jason; Fagan, Anne M; Benzinger, Tammie L S; Grant, Elizabeth A; Holtzman, David M; Morris, John C; Roe, Catherine M

2016-01-01

The influence of reserve variables and Alzheimer's disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on "non-cognitive" outcomes, including functional abilities and mood. We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD.

Does changing from a first generation antipsychotic (perphenazin) to a second generation antipsychotic (risperidone) alter brain activation and motor activity? A case report

PubMed Central

2013-01-01

Background In patients with schizophrenia, altered brain activation and motor activity levels are central features, reflecting cognitive impairments and negative symptoms, respectively. Newer studies using nonlinear methods have addressed the severe disturbances in neurocognitive functioning that is regarded as one of the core features of schizophrenia. Our aim was to compare brain activation and motor activity in a patient during pharmacological treatment that was switched from a first- to a second-generation antipsychotic drug. We hypothesised that this change of medication would increase level of responding in both measures. Case presentation We present the case of a 53-year-old male with onset of severe mental illness in adolescence, ICD-10 diagnosed as schizophrenia of paranoid type, chronic form. We compared brain activation and motor activity in this patient during pharmacological treatment with a first-generation (perphenazin), and later switched to a second-generation (risperidone) antipsychotic drug. We used functional magnetic resonance imaging (fMRI) to measure brain activation and wrist worn actigraphy to measure motor activity. Conclusion Our study showed that brain activation decreased in areas critical for cognitive functioning in this patient, when changing from a first to a second generation antipsychotic drug. However the mean motor activity level was unchanged, although risperidone reduced variability, particularly short-term variability from minute to minute. Compared to the results from previous studies, the present findings indicate that changing to a second-generation antipsychotic alters variability measures towards that seen in a control group, but with reduced brain activation, which was an unexpected finding. PMID:23648137

Does changing from a first generation antipsychotic (perphenazin) to a second generation antipsychotic (risperidone) alter brain activation and motor activity? A case report.

PubMed

Berle, Jan Øystein; Løberg, Else-Marie; Fasmer, Ole Bernt

2013-05-06

In patients with schizophrenia, altered brain activation and motor activity levels are central features, reflecting cognitive impairments and negative symptoms, respectively. Newer studies using nonlinear methods have addressed the severe disturbances in neurocognitive functioning that is regarded as one of the core features of schizophrenia. Our aim was to compare brain activation and motor activity in a patient during pharmacological treatment that was switched from a first- to a second-generation antipsychotic drug. We hypothesised that this change of medication would increase level of responding in both measures. We present the case of a 53-year-old male with onset of severe mental illness in adolescence, ICD-10 diagnosed as schizophrenia of paranoid type, chronic form. We compared brain activation and motor activity in this patient during pharmacological treatment with a first-generation (perphenazin), and later switched to a second-generation (risperidone) antipsychotic drug. We used functional magnetic resonance imaging (fMRI) to measure brain activation and wrist worn actigraphy to measure motor activity. Our study showed that brain activation decreased in areas critical for cognitive functioning in this patient, when changing from a first to a second generation antipsychotic drug. However the mean motor activity level was unchanged, although risperidone reduced variability, particularly short-term variability from minute to minute. Compared to the results from previous studies, the present findings indicate that changing to a second-generation antipsychotic alters variability measures towards that seen in a control group, but with reduced brain activation, which was an unexpected finding.

The neurobiology of addiction: the perspective from magnetic resonance imaging present and future.

PubMed

Suckling, John; Nestor, Liam J

2017-02-01

Addiction is associated with severe economic and social consequences and personal tragedies, the scientific exploration of which draws upon investigations at the molecular, cellular and systems levels with a wide variety of technologies. Magnetic resonance imaging (MRI) has been key to mapping effects observed at the microscopic and mesoscopic scales. The range of measurements from this apparatus has opened new avenues linking neurobiology to behaviour. This review considers the role of MRI in addiction research, and what future technological improvements might offer. A hermeneutic strategy supplemented by an expansive, systematic search of PubMed, Scopus and Web of Science databases, covering from database inception to October 2015, with a conjunction of search terms relevant to addiction and MRI. Formal meta-analyses were prioritized. Results from methods that probe brain structure and function suggest frontostriatal circuitry disturbances within specific cognitive domains, some of which predict drug relapse and treatment response. New methods of processing imaging data are opening opportunities for understanding the role of cerebral vasculature, a global view of brain communication and the complex topology of the cortical surface and drug action. Future technological advances include increases in MRI field strength, with concomitant improvements in image quality. The magnetic resonance imaging literature provides a limited but convergent picture of the neurobiology of addiction as global changes to brain structure and functional disturbances to frontostriatal circuitry, accompanied by changes in anterior white matter. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Omega-3 fatty acids and brain resistance to ageing and stress: body of evidence and possible mechanisms.

PubMed

Denis, I; Potier, B; Vancassel, S; Heberden, C; Lavialle, M

2013-03-01

The increasing life expectancy in the populations of rich countries raises the pressing question of how the elderly can maintain their cognitive function. Cognitive decline is characterised by the loss of short-term memory due to a progressive impairment of the underlying brain cell processes. Age-related brain damage has many causes, some of which may be influenced by diet. An optimal diet may therefore be a practical way of delaying the onset of age-related cognitive decline. Nutritional investigations indicate that the ω-3 poyunsaturated fatty acid (PUFA) content of western diets is too low to provide the brain with an optimal supply of docosahexaenoic acid (DHA), the main ω-3 PUFA in cell membranes. Insufficient brain DHA has been associated with memory impairment, emotional disturbances and altered brain processes in rodents. Human studies suggest that an adequate dietary intake of ω-3 PUFA can slow the age-related cognitive decline and may also protect against the risk of senile dementia. However, despite the many studies in this domain, the beneficial impact of ω-3 PUFA on brain function has only recently been linked to specific mechanisms. This review examines the hypothesis that an optimal brain DHA status, conferred by an adequate ω-3 PUFA intake, limits age-related brain damage by optimizing endogenous brain repair mechanisms. Our analysis of the abundant literature indicates that an adequate amount of DHA in the brain may limit the impact of stress, an important age-aggravating factor, and influences the neuronal and astroglial functions that govern and protect synaptic transmission. This transmission, particularly glutamatergic neurotransmission in the hippocampus, underlies memory formation. The brain DHA status also influences neurogenesis, nested in the hippocampus, which helps maintain cognitive function throughout life. Although there are still gaps in our knowledge of the way ω-3 PUFA act, the mechanistic studies reviewed here indicate that ω-3 PUFA may be a promising tool for preventing age-related brain deterioration. Copyright © 2013 Elsevier B.V. All rights reserved.

Neurobiology of anorexia and bulimia nervosa.

PubMed

Kaye, Walter

2008-04-22

Anorexia nervosa (AN) and bulimia nervosa (BN) are related disorders of unknown etiology that most commonly begin during adolescence in women. AN and BN have unique and puzzling symptoms, such as restricted eating or binge-purge behaviors, body image distortions, denial of emaciation, and resistance to treatment. These are often chronic and relapsing disorders, and AN has the highest death rate of any psychiatric disorder. The lack of understanding of the pathogenesis of this illness has hindered the development of effective interventions, particularly for AN. Individuals with AN and BN are consistently characterized by perfectionism, obsessive-compulsiveness, and dysphoric mood. Individuals with AN tend to have high constraint, constriction of affect and emotional expressiveness, ahendonia and asceticism, whereas individuals with BN tend to be more impulsive and sensation seeking. Such symptoms often begin in childhood, before the onset of an eating disorder, and persist after recovery, suggesting they are traits that create a vulnerability for developing an ED. There is growing acknowledgement that neurobiological vulnerabilities make a substantial contribution to the pathogenesis of AN and BN. Considerable evidence suggests that altered brain serotonin (5-HT) function contributes to dysregulation of appetite, mood, and impulse control in AN and BN. Brain imaging studies, using 5-HT specific ligands, show that disturbances of 5-HT function occur when people are ill, and persist after recovery from AN and BN. It is possible that a trait-related disturbance of 5-HT neuronal modulation predates the onset of AN and contributes to premorbid symptoms of anxiety, obsessionality, and inhibition. This dysphoric temperament may involve an inherent dysregulation of emotional and reward pathways which also mediate the hedonic aspects of feeding, thus making these individuals vulnerable to disturbed appetitive behaviors. Restricting food intake may become powerfully reinforcing because it provides a temporary respite from dysphoric mood. Several factors may act on these vulnerabilities to cause AN to start in adolescence. First, puberty-related female gonadal steroids or age-related changes may exacerbate 5-HT dysregulation. Second, stress and/or cultural and societal pressures may contribute by increasing anxious and obsessional temperament. Individuals with AN may discover that reduced dietary intake, by reducing plasma tryptophan availability, is a means by which they can modulate brain 5-HT functional activity and anxious mood. People with AN enter a vicious cycle which accounts for the chronicity of this disorder because caloric restriction results in a brief respite from dysphoric mood. However, malnutrition and weight loss, in turn, produce alterations in many neuropeptides and monoamine function, perhaps in the service of conserving energy, but which also exaggerates dysphoric mood. In summary, this article reviews findings in brain chemistry and neuroimaging that shed new light on understanding the psychopathology of these difficult and frustrating disorders.

Pathogenesis of Hepatic Encephalopathy

PubMed Central

Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

2012-01-01

Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

Diagnostic work up for language testing in patients undergoing awake craniotomy for brain lesions in language areas.

PubMed

Bilotta, Federico; Stazi, Elisabetta; Titi, Luca; Lalli, Diana; Delfini, Roberto; Santoro, Antonio; Rosa, Giovanni

2014-06-01

Awake craniotomy is the technique of choice in patients with brain tumours adjacent to primary and accessory language areas (Broca's and Wernicke's areas). Language testing should be aimed to detect preoperative deficits, to promptly identify the occurrence of new intraoperative impairments and to establish the course of postoperative language status. Aim of this case series is to describe our experience with a dedicated language testing work up to evaluate patients with or at risk for language disturbances undergoing awake craniotomy for brain tumour resection. Pre- and intra operative testing was accomplished with 8 tests. Intraoperative evaluation was accomplished when patients were fully cooperative (Ramsey < 3). Postoperative evaluation was scheduled at early (within 21 days) and long-term follow-up (3-6 months). Twenty consecutive patients were prospectively recruited. Preoperative language testings were normal in 9 patients (45%), showed mild to moderate language deficit in 8 (40%) and severe language deficit or aphasic disorders in 3 (15%). Broca's area was identified in 15 patients, in all cases by counting arrest during stimulation and in 12 cases by naming arrest. In this article we describe our experience using a language testing work up to evaluate - pre, intra and postoperatively - patients undergoing awake craniotomy for brain tumour resection with preoperative language disturbances or at risk for postoperative language deficits. This approach allows a systematic evaluation and recording of language function status and can be accomplished even when a neuropsychologist or speech therapist are not involved in the operation crew.

Functional resting-state networks are differentially affected in schizophrenia

PubMed Central

Woodward, Neil D.; Rogers, Baxter; Heckers, Stephan

2011-01-01

Neurobiological theories posit that schizophrenia relates to disturbances in connectivity between brain regions. Resting-state functional magnetic resonance imaging is a powerful tool for examining functional connectivity and has revealed several canonical brain networks, including the default mode, dorsal attention, executive control, and salience networks. The purpose of this study was to examine changes in these networks in schizophrenia. 42 patients with schizophrenia and 61 healthy subjects completed a RS-fMRI scanning session. Seed-based region-of-interest correlation analysis was used to identify the default mode, dorsal attention, executive control, and salience networks. Compared to healthy subjects, individuals with schizophrenia demonstrated greater connectivity between the posterior cingulate cortex, a key hub of the default mode, and the left inferior gyrus, left middle frontal gyrus, and left middle temporal gyrus. Interestingly, these regions were more strongly connected to the executive control network in healthy control subjects. In contrast to the default mode, patients demonstrated less connectivity in the executive control and dorsal attention networks. No differences were observed in the salience network. The results indicate that resting-state networks are differentially affected in schizophrenia. The alterations are characterized by reduced segregation between the default mode and executive control networks in the prefrontal cortex and temporal lobe, and reduced connectivity in the dorsal attention and executive control networks. The changes suggest that the process of functional specialization is altered in schizophrenia. Further work is needed to determine if the alterations are related to disturbances in white matter connectivity, neurodevelopmental abnormalities, and genetic risk for schizophrenia. PMID:21458238

Intrinsic brain abnormalities in young healthy adults with childhood trauma: A resting-state functional magnetic resonance imaging study of regional homogeneity and functional connectivity.

PubMed

Lu, Shaojia; Gao, Weijia; Wei, Zhaoguo; Wang, Dandan; Hu, Shaohua; Huang, Manli; Xu, Yi; Li, Lingjiang

2017-06-01

Childhood trauma confers great risk for the development of multiple psychiatric disorders; however, the neural basis for this association is still unknown. The present resting-state functional magnetic resonance imaging study aimed to detect the effects of childhood trauma on brain function in a group of young healthy adults. In total, 24 healthy individuals with childhood trauma and 24 age- and sex-matched adults without childhood trauma were recruited. Each participant underwent resting-state functional magnetic resonance imaging scanning. Intra-regional brain activity was evaluated by regional homogeneity method and compared between groups. Areas with altered regional homogeneity were further selected as seeds in subsequent functional connectivity analysis. Statistical analyses were performed by setting current depression and anxiety as covariates. Adults with childhood trauma showed decreased regional homogeneity in bilateral superior temporal gyrus and insula, and the right inferior parietal lobule, as well as increased regional homogeneity in the right cerebellum and left middle temporal gyrus. Regional homogeneity values in the left middle temporal gyrus, right insula and right cerebellum were correlated with childhood trauma severity. In addition, individuals with childhood trauma also exhibited altered default mode network, cerebellum-default mode network and insula-default mode network connectivity when the left middle temporal gyrus, right cerebellum and right insula were selected as seed area, respectively. The present outcomes suggest that childhood trauma is associated with disturbed intrinsic brain function, especially the default mode network, in adults even without psychiatric diagnoses, which may mediate the relationship between childhood trauma and psychiatric disorders in later life.

Repetitive Traumatic Brain Injury (or Concussion) Increases Severity of Sleep Disturbance among Deployed Military Personnel

PubMed Central

Bryan, Craig J.

2013-01-01

Study Objectives: Considerable research indicates that sleep disturbances and insomnia are more common and severe among individuals following a traumatic brain injury (TBI). It remains unclear, however, how the experience of multiple TBIs affect sleep disturbances and insomnia. The current study investigated the incidence and severity of insomnia and sleep complaints among active-duty military personnel who have sustained multiple TBIs. Design and Setting: Upon intake at a military TBI clinic located in Iraq, 150 male military patients completed standardized self-report measures and clinical interviews. Measurements and Results: Patients were categorized into three groups according to history of TBI: zero TBIs (n = 18), single TBI (n = 54), multiple TBIs (n = 78). Rates of clinical insomnia significantly increased across TBI groups (P < 0.001):- 5.6% for no TBIs, 20.4% for single TBI, and 50.0% for multiple TBIs. Insomnia severity significantly increased across TBI groups even when controlling for depression, posttraumatic stress disorder, and concussion symptom severity (B = 1.134, standard error = 0.577, P = 0.049). Conclusions: Multiple TBIs are associated with increased risk for and severity of sleep disturbance among male military personnel. Citation: Bryan CJ. Repetitive traumatic brain injury (or concussion) increases severity of sleep disturbance among deployed military personnel. SLEEP 2013;36(6):941-946. PMID:23729938

Sleep-wake functions and quality of life in patients with subthalamic deep brain stimulation for Parkinson’s disease

PubMed Central

Eugster, Lukas; Oberholzer, Michael; Debove, Ines; Lachenmayer, M. Lenard; Mathis, Johannes; Pollo, Claudio; Schüpbach, W. M. Michael; Bassetti, Claudio L.

2017-01-01

Objectives Sleep-wake disturbances (SWD) are frequent in Parkinson’s disease (PD). The effect of deep brain stimulation (DBS) on SWD is poorly known. In this study we examined the subjective and objective sleep-wake profile and the quality of life (QoL) of PD patients in the context of subthalamic DBS. Patients and methods We retrospectively analyzed data from PD patients and candidates for DBS in the nucleus suthalamicus (STN). Pre-DBS, sleep-wake assessments included subjective and objective (polysomnography, vigilance tests and actigraphy) measures. Post-DBS, subjective measures were collected. QoL was assessed using the Parkinson’s Disease Questionnaire (PDQ-39) and the RAND SF-36-item Health Survey (RAND SF-36). Results Data from 74 PD patients (62% male, mean age 62.2 years, SD = 8.9) with a mean UPDRS-III (OFF) of 34.2 (SD = 14.8) and 11.8 (SD = 4.5) years under PD treatment were analyzed. Pre-DBS, daytime sleepiness, apathy, fatigue and depressive symptoms were present in 49%, 34%, 38% and 25% of patients respectively but not always as co-occurring symptoms. Sleep-wake disturbances were significantly correlated with QoL scores. One year after STN DBS, motor signs, QoL and sleepiness improved but apathy worsened. Changes in QoL were associated with changes in sleepiness and apathy but baseline sleep-wake functions were not predictive of STN DBS outcome. Conclusion In PD patients presenting for STN DBS, subjective and objective sleep-wake disturbances are common and have a negative impact on QoL before and after neurosurgery. Given the current preliminary evidence, prospective observational studies assessing subjective and objective sleep-wake variables prior to and after DBS are needed. PMID:29253029

Neuroimaging Studies of Normal Brain Development and Their Relevance for Understanding Childhood Neuropsychiatric Disorders

ERIC Educational Resources Information Center

Marsh, Rachel; Gerber, Andrew J.; Peterson, Bradley S.

2008-01-01

Neuroimaging findings which identify normal brain development trajectories are presented. Results show that early brain development begins with the neural tube formation and ends with myelintation. How disturbances in brain development patterns are related to childhood psychiatric disorders is examined.

Monitoring fetal maturation—objectives, techniques and indices of autonomic function*

PubMed Central

Hoyer, Dirk; Żebrowski, Jan; Cysarz, Dirk; Gonçalves, Hernâni; Pytlik, Adelina; Amorim-Costa, Célia; Bernardes, João; Ayres-de-Campos, Diogo; Witte, Otto W; Schleußner, Ekkehard; Stroux, Lisa; Redman, Christopher; Georgieva, Antoniya; Payne, Stephen; Clifford, Gari; Signorini, Maria G; Magenes, Giovanni; Andreotti, Fernando; Malberg, Hagen; Zaunseder, Sebastian; Lakhno, Igor; Schneider, Uwe

2017-01-01

Objective Monitoring the fetal behavior does not only have implications for acute care but also for identifying developmental disturbances that burden the entire later life. The concept, of ‘fetal programming’, also known as ‘developmental origins of adult disease hypothesis’, e.g. applies for cardiovascular, metabolic, hyperkinetic, cognitive disorders. Since the autonomic nervous system is involved in all of those systems, cardiac autonomic control may provide relevant functional diagnostic and prognostic information. Approach The fetal heart rate patterns (HRP) are one of the few functional signals in the prenatal period that relate to autonomic control and, therefore, is key to fetal autonomic assessment. The development of sensitive markers of fetal maturation and its disturbances requires the consideration of physiological fundamentals, recording technology and HRP parameters of autonomic control. Main Results Based on the ESGCO2016 special session on monitoring the fetal maturation we herein report the most recent results on: (i) functional fetal autonomic brain age score (fABAS), Recurrence Quantitative Analysis and Binary Symbolic Dynamics of complex HRP resolve specific maturation periods, (ii) magnetocardiography (MCG) based fABAS was validated for cardiotocography (CTG), (iii) 30 min recordings are sufficient for obtaining episodes of high variability, important for intrauterine growth restriction (IUGR) detection in handheld Doppler, (iv) novel parameters from PRSA to identify Intra IUGR fetuses, (v) evaluation of fetal electrocardiographic (ECG) recordings, (vi) correlation between maternal and fetal HRV is disturbed in pre-eclampsia. Significance The reported novel developments significantly extend the possibilities for the established CTG methodology. Novel HRP indices improve the accuracy of assessment due to their more appropriate consideration of complex autonomic processes across the recording technologies (CTG, handheld Doppler, MCG, ECG). The ultimate objective is their dissemination into routine practice and studies of fetal developmental disturbances with implications for programming of adult diseases. PMID:28186000

Functional approach using intraoperative brain mapping and neurophysiological monitoring for the surgical treatment of brain metastases in the central region.

PubMed

Sanmillan, Jose L; Fernández-Coello, Alejandro; Fernández-Conejero, Isabel; Plans, Gerard; Gabarrós, Andreu

2017-03-01

OBJECTIVE Brain metastases are the most frequent intracranial malignant tumor in adults. Surgical intervention for metastases in eloquent areas remains controversial and challenging. Even when metastases are not infiltrating intra-parenchymal tumors, eloquent areas can be affected. Therefore, this study aimed to describe the role of a functional guided approach for the resection of brain metastases in the central region. METHODS Thirty-three patients (19 men and 14 women) with perirolandic metastases who were treated at the authors' institution were reviewed. All participants underwent resection using a functional guided approach, which consisted of using intraoperative brain mapping and/or neurophysiological monitoring to aid in the resection, depending on the functionality of the brain parenchyma surrounding each metastasis. Motor and sensory functions were monitored in all patients, and supplementary motor and language area functions were assessed in 5 and 4 patients, respectively. Clinical data were analyzed at presentation, discharge, and the 6-month follow-up. RESULTS The most frequent presenting symptom was seizure, followed by paresis. Gross-total removal of the metastasis was achieved in 31 patients (93.9%). There were 6 deaths during the follow-up period. After the removal of the metastasis, 6 patients (18.2%) presented with transient neurological worsening, of whom 4 had worsening of motor function impairment and 2 had acquired new sensory disturbances. Total recovery was achieved before the 3rd month of follow-up in all cases. Excluding those patients who died due to the progression of systemic illness, 88.9% of patients had a Karnofsky Performance Scale score greater than 80% at the 6-month follow-up. The mean survival time was 24.4 months after surgery. CONCLUSIONS The implementation of intraoperative electrical brain stimulation techniques in the resection of central region metastases may improve surgical planning and resection and may spare eloquent areas. This approach also facilitates maximal resection in these and other critical functional areas, thereby helping to avoid new postoperative neurological deficits. Avoiding permanent neurological deficits is critical for a good quality of life, especially in patients with a life expectancy of over a year.

Disrupted Topological Patterns of Large-Scale Network in Conduct Disorder

PubMed Central

Jiang, Yali; Liu, Weixiang; Ming, Qingsen; Gao, Yidian; Ma, Ren; Zhang, Xiaocui; Situ, Weijun; Wang, Xiang; Yao, Shuqiao; Huang, Bingsheng

2016-01-01

Regional abnormalities in brain structure and function, as well as disrupted connectivity, have been found repeatedly in adolescents with conduct disorder (CD). Yet, the large-scale brain topology associated with CD is not well characterized, and little is known about the systematic neural mechanisms of CD. We employed graphic theory to investigate systematically the structural connectivity derived from cortical thickness correlation in a group of patients with CD (N = 43) and healthy controls (HCs, N = 73). Nonparametric permutation tests were applied for between-group comparisons of graphical metrics. Compared with HCs, network measures including global/local efficiency and modularity all pointed to hypo-functioning in CD, despite of preserved small-world organization in both groups. The hubs distribution is only partially overlapped with each other. These results indicate that CD is accompanied by both impaired integration and segregation patterns of brain networks, and the distribution of highly connected neural network ‘hubs’ is also distinct between groups. Such misconfiguration extends our understanding regarding how structural neural network disruptions may underlie behavioral disturbances in adolescents with CD, and potentially, implicates an aberrant cytoarchitectonic profiles in the brain of CD patients. PMID:27841320

Cognition and Resting-State Functional Connectivity in Schizophrenia

PubMed Central

Sheffield, Julia M; Barch, Deanna M

2015-01-01

Individuals with schizophrenia consistently display deficits in a multitude of cognitive domains, but the neurobiological source of these cognitive impairments remains unclear. By analyzing the functional connectivity of resting-state functional magnetic resonance imaging (rs-fcMRI) data in clinical populations like schizophrenia, research groups have begun elucidating abnormalities in the intrinsic communication between specific brain regions, and assessing relationships between these abnormalities and cognitive performance in schizophrenia. Here we review studies that have reported analysis of these brain-behavior relationships. Through this systematic review we found that patients with schizophrenia display abnormalities within and between regions comprising 1) the cortico-cerebellar-striatal-thalamic loop and 2) task-positive and task-negative cortical networks. Importantly, we did not observe unique relationships between specific functional connectivity abnormalities and distinct cognitive domains, suggesting that the observed functional systems may underlie mechanisms that are shared across cognitive abilities, the disturbance of which could contribute to the “generalized” cognitive deficit found in schizophrenia. We also note several areas of methodological change that we believe will strengthen this literature. PMID:26698018

Thyroid Hormone in the CNS: Contribution of Neuron-Glia Interaction.

PubMed

Noda, Mami

2018-01-01

The endocrine system and the central nervous system (CNS) are intimately linked. Among hormones closely related to the nervous system, thyroid hormones (THs) are critical for the regulation of development and differentiation of neurons and neuroglia and hence for development and function of the CNS. T3 (3,3',5-triiodothyronine), an active form of TH, is important not only for neuronal development but also for differentiation of astrocytes and oligodendrocytes, and for microglial development. In adult brain, T3 affects glial morphology with sex- and age-dependent manner and therefore may affect their function, leading to influence on neuron-glia interaction. T3 is an important signaling factor that affects microglial functions such as migration and phagocytosis via complex mechanisms. Therefore, dysfunction of THs may impair glial function as well as neuronal function and thus disturb the brain, which may cause mental disorders. Investigations on molecular and cellular basis of hyperthyroidism and hypothyroidism will help us to understand changes in neuron-glia interaction and therefore consequent psychiatric symptoms. © 2018 Elsevier Inc. All rights reserved.

The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study.

PubMed

de Waal, Hanneke; Stam, Cornelis J; Lansbergen, Marieke M; Wieggers, Rico L; Kamphuis, Patrick J G H; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C W

2014-01-01

Synaptic loss is a major hallmark of Alzheimer's disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. 179 drug-naïve mild AD patients who participated in the Souvenir II study. Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. THE NETWORK MEASURES IN THE BETA BAND WERE SIGNIFICANTLY DIFFERENT BETWEEN GROUPS: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Dutch Trial Register NTR1975.

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

PubMed Central

de Waal, Hanneke; Stam, Cornelis J.; Lansbergen, Marieke M.; Wieggers, Rico L.; Kamphuis, Patrick J. G. H.; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C. W.

2014-01-01

Background Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. Objective To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. Design A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. Participants 179 drug-naïve mild AD patients who participated in the Souvenir II study. Intervention Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. Outcome In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. Results The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. Conclusions The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Trial registration Dutch Trial Register NTR1975. PMID:24475144

Morphology of subcortical brain nuclei is associated with autonomic function in healthy humans.

PubMed

Ruffle, James K; Coen, Steven J; Giampietro, Vincent; Williams, Steven C R; Apkarian, A Vania; Farmer, Adam D; Aziz, Qasim

2018-01-01

The autonomic nervous system (ANS) is a brain body interface which serves to maintain homeostasis by influencing a plethora of physiological processes, including metabolism, cardiorespiratory regulation and nociception. Accumulating evidence suggests that ANS function is disturbed in numerous prevalent clinical disorders, including irritable bowel syndrome and fibromyalgia. While the brain is a central hub for regulating autonomic function, the association between resting autonomic activity and subcortical morphology has not been comprehensively studied and thus was our aim. In 27 healthy subjects [14 male and 13 female; mean age 30 years (range 22-53 years)], we quantified resting ANS function using validated indices of cardiac sympathetic index (CSI) and parasympathetic cardiac vagal tone (CVT). High resolution structural magnetic resonance imaging scans were acquired, and differences in subcortical nuclei shape, that is, 'deformation', contingent on resting ANS activity were investigated. CSI positively correlated with outward deformation of the brainstem, right nucleus accumbens, right amygdala and bilateral pallidum (all thresholded to corrected P < 0.05). In contrast, parasympathetic CVT negatively correlated with inward deformation of the right amygdala and pallidum (all thresholded to corrected P < 0.05). Left and right putamen volume positively correlated with CVT (r = 0.62, P = 0.0047 and r = 0.59, P = 0.008, respectively), as did the brainstem (r = 0.46, P = 0.049). These data provide novel evidence that resting autonomic state is associated with differences in the shape and volume of subcortical nuclei. Thus, subcortical morphological brain differences in various disorders may partly be attributable to perturbation in autonomic function. Further work is warranted to investigate these findings in clinical populations. Hum Brain Mapp 39:381-392, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The brain network reflecting bodily self-consciousness: a functional connectivity study

PubMed Central

Ionta, Silvio; Martuzzi, Roberto; Salomon, Roy

2014-01-01

Several brain regions are important for processing self-location and first-person perspective, two important aspects of bodily self-consciousness. However, the interplay between these regions has not been clarified. In addition, while self-location and first-person perspective in healthy subjects are associated with bilateral activity in temporoparietal junction (TPJ), disturbed self-location and first-person perspective result from damage of only the right TPJ. Identifying the involved brain network and understanding the role of hemispheric specializations in encoding self-location and first-person perspective, will provide important information on system-level interactions neurally mediating bodily self-consciousness. Here, we used functional connectivity and showed that right and left TPJ are bilaterally connected to supplementary motor area, ventral premotor cortex, insula, intraparietal sulcus and occipitotemporal cortex. Furthermore, the functional connectivity between right TPJ and right insula had the highest selectivity for changes in self-location and first-person perspective. Finally, functional connectivity revealed hemispheric differences showing that self-location and first-person perspective modulated the connectivity between right TPJ, right posterior insula, and right supplementary motor area, and between left TPJ and right anterior insula. The present data extend previous evidence on healthy populations and clinical observations in neurological deficits, supporting a bilateral, but right-hemispheric dominant, network for bodily self-consciousness. PMID:24396007

Genetic defects disrupting glial ion and water homeostasis in the brain.

PubMed

Min, Rogier; van der Knaap, Marjo S

2018-05-01

Electrical activity of neurons in the brain, caused by the movement of ions between intracellular and extracellular compartments, is the basis of all our thoughts and actions. Maintaining the correct ionic concentration gradients is therefore crucial for brain functioning. Ion fluxes are accompanied by the displacement of osmotically obliged water. Since even minor brain swelling leads to severe brain damage and even death, brain ion and water movement has to be tightly regulated. Glial cells, in particular astrocytes, play a key role in ion and water homeostasis. They are endowed with specific channels, pumps and carriers to regulate ion and water flow. Glial cells form a large panglial syncytium to aid the uptake and dispersal of ions and water, and make extensive contacts with brain fluid barriers for disposal of excess ions and water. Genetic defects in glial proteins involved in ion and water homeostasis disrupt brain functioning, thereby leading to neurological diseases. Since white matter edema is often a hallmark disease feature, many of these diseases are characterized as leukodystrophies. In this review we summarize our current understanding of inherited glial diseases characterized by disturbed brain ion and water homeostasis by integrating findings from MRI, genetics, neuropathology and animal models for disease. We discuss how mutations in different glial proteins lead to disease, and highlight the similarities and differences between these diseases. To come to effective therapies for this group of diseases, a better mechanistic understanding of how glial cells shape ion and water movement in the brain is crucial. © 2018 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.

Neuropsychology of humor: an introduction. Part II. Humor and the brain.

PubMed

Derouesné, Christian

2016-09-01

Impairment of the perception or comprehension of humor is observed in patients with focal brain lesions in both hemispheres, but mainly in the right frontal lobe. Studies by functional magnetic resonance imaging in healthy subjects show that humor is associated with activation of two main neural systems in both hemispheres. The detection and resolution of incongruity, cognitive groundings of humor, are associated with activation of the medial prefrontal and temporoparietal cortex, and the humor appreciation with activation of the orbito-frontal and insular cortex, amygdala and the brain reward system. However, activation of these areas is not humor-specific and can be observed in various cognitive or emotional processes. Event-related potential studies confirm the involvement of both hemispheres in humor processing, and suggest that left prefrontal area is associated with joke comprehension and right prefrontal area with the resolution stage. Humor thus appears to be a complex and dynamic functional process involving, on one hand, two specialized but not specific neural systems linked to humor apprehension and appreciation, and, on the other hand, multiple interconnected functional brain networks including neural patterns underlying the moral framework and belief system, acquired by conditioning or imitation during the cognitive development and social interactions of the individual, and more distributed systems associated with the analysis of the current context of humor occurrence. Disturbances of the sense of humor could then result from focal brain alterations localized in one or two of the specialized areas underlying the comprehension or appreciation of humor, or from perturbations of the network interconnectivity in non-focal brain disorders such as Alzheimer's disease or schizophrenia.

Vulnerability of children and the developing brain to neurotoxic hazards.

PubMed

Weiss, B

2000-06-01

For much of the history of toxicology, the sensitivity of the developing organism to chemical perturbation attracted limited attention. Several tragic episodes and new insights finally taught us that the course of early brain development incurs unique risks. Although the process is exquisitely controlled, its lability renders it highly susceptible to damage from environmental chemicals. Such disturbances, as recognized by current testing protocols and legislation such as the Food Quality Protection Act, can result in outcomes ranging from death to malformations to functional impairment. The latter are the most difficult to determine. First, they require a variety of measures to assay their extent. Second, adult responses may prove an inadequate guide to the response of the developing brain, which is part of the reason for proposing additional safety factors for children. Third, neuropsychological tests are deployed in complex circumstances in which many factors, including economic status, combine to produce a particular effect such as lowered intelligence quotient score. Fourth, the magnitude of the effect, for most environmental exposure levels, may be relatively small but extremely significant for public health. Fifth, changes in brain function occur throughout life, and some consequences of early damage may not even emerge until advanced age. Such factors need to be addressed in estimating the influence of a particular agent or group of agents on brain development and its functional expression. It is especially important to consider ways of dealing with multiple risks and their combinations in addition to the prevailing practice of estimating risks in isolation.

Changes in the central nervous system during long-duration space flight: implications for neuro-imaging

NASA Astrophysics Data System (ADS)

Newberg, A. B.; Alavi, A.

The purpose of this paper is to review the potential functional and morphological effects of long duration space flight on the human central nervous system (CNS) and how current neuroimaging techniques may be utilized to study these effects. It must be determined if there will be any detrimental changes to the CNS from long term exposure to the space environment if human beings are to plan interplanetary missions or establish permanent space habitats. Research to date has focused primarily on the short term changes in the CNS as the result of space flight. The space environment has many factors such as weightlessness, electromagnetic fields, and radiation, that may impact upon the function and structure of the CNS. CNS changes known to occur during and after long term space flight include neurovestibular disturbances, cephalic fluid shifts, alterations in sensory perception, changes in proprioception, psychological disturbances, and cognitive changes. Animal studies have shown altered plasticity of the neural cytoarchitecture, decreased neuronal metabolism in the hypothalamus, and changes in neurotransmitter concentrations. Recent progress in the ability to study brain morphology, cerebral metabolism, and neurochemistry in vivo in the human brain would provide ample opportunity to investigate many of the changes that occur in the CNS as a result of space flight. These methods include positron emission tomography (PET), single photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI).

Altered Effective Connectivity among Core Neurocognitive Networks in Idiopathic Generalized Epilepsy: An fMRI Evidence

PubMed Central

Wei, Huilin; An, Jie; Shen, Hui; Zeng, Ling-Li; Qiu, Shijun; Hu, Dewen

2016-01-01

Idiopathic generalized epilepsy (IGE) patients with generalized tonic-clonic seizures (GTCS) suffer long-term cognitive impairments, and present a higher incidence of psychosocial and psychiatric disturbances than healthy people. It is possible that the cognitive dysfunctions and higher psychopathological risk in IGE-GTCS derive from disturbed causal relationship among core neurocognitive brain networks. To test this hypothesis, we examined the effective connectivity across the salience network (SN), default mode network (DMN), and central executive network (CEN) using resting-state functional magnetic resonance imaging (fMRI) data collected from 27 IGE-GTCS patients and 29 healthy controls. In the study, a combination framework of time domain and frequency domain multivariate Granger causality analysis was firstly proposed, and proved to be valid and accurate by simulation experiments. Using this method, we then observed significant differences in the effective connectivity graphs between the patient and control groups. Specifically, between-group statistical analysis revealed that relative to the healthy controls, the patients established significantly enhanced Granger causal influence from the dorsolateral prefrontal cortex to the dorsal anterior cingulate cortex, which is coherent both in the time and frequency domains analyses. Meanwhile, time domain analysis also revealed decreased Granger causal influence from the right fronto-insular cortex to the posterior cingulate cortex in the patients. These findings may provide new evidence for functional brain organization disruption underlying cognitive dysfunctions and psychopathological risk in IGE-GTCS. PMID:27656137

Disturbed resting state EEG synchronization in bipolar disorder: A graph-theoretic analysis☆

PubMed Central

Kim, Dae-Jin; Bolbecker, Amanda R.; Howell, Josselyn; Rass, Olga; Sporns, Olaf; Hetrick, William P.; Breier, Alan; O'Donnell, Brian F.

2013-01-01

Disruption of functional connectivity may be a key feature of bipolar disorder (BD) which reflects disturbances of synchronization and oscillations within brain networks. We investigated whether the resting electroencephalogram (EEG) in patients with BD showed altered synchronization or network properties. Resting-state EEG was recorded in 57 BD type-I patients and 87 healthy control subjects. Functional connectivity between pairs of EEG channels was measured using synchronization likelihood (SL) for 5 frequency bands (δ, θ, α, β, and γ). Graph-theoretic analysis was applied to SL over the electrode array to assess network properties. BD patients showed a decrease of mean synchronization in the alpha band, and the decreases were greatest in fronto-central and centro-parietal connections. In addition, the clustering coefficient and global efficiency were decreased in BD patients, whereas the characteristic path length increased. We also found that the normalized characteristic path length and small-worldness were significantly correlated with depression scores in BD patients. These results suggest that BD patients show impaired neural synchronization at rest and a disruption of resting-state functional connectivity. PMID:24179795

Depression-like behaviour in mice is associated with disrupted circadian rhythms in nucleus accumbens and periaqueductal grey.

PubMed

Landgraf, Dominic; Long, Jaimie E; Welsh, David K

2016-05-01

An association between circadian rhythms and mood regulation is well established, and disturbed circadian clocks are believed to contribute to the development of mood disorders, including major depressive disorder. The circadian system is coordinated by the suprachiasmatic nucleus (SCN), the master pacemaker in the hypothalamus that receives light input from the retina and synchronizes circadian oscillators in other brain regions and peripheral tissues. Lacking the tight neuronal network that couples single-cell oscillators in the SCN, circadian clocks outside the SCN may be less stable and more susceptible to disturbances, for example by clock gene mutations or uncontrollable stress. However, non-SCN circadian clocks have not been studied extensively in rodent models of mood disorders. In the present study, it was hypothesized that disturbances of local circadian clocks in mood-regulating brain areas are associated with depression-like behaviour in mice. Using the learned helplessness procedure, depression-like behaviour was evoked in mice bearing the PER2::LUC circadian reporter, and then circadian rhythms of PER2 expression were examined in brain slices from these mice using luminometry and bioluminescence imaging. It was found that helplessness is associated with absence of circadian rhythms in the nucleus accumbens and the periaqueductal grey, two of the most critical brain regions within the reward circuit. The current study provides evidence that susceptibility of mice to depression-like behaviour is associated with disturbed local circadian clocks in a subset of mood-regulating brain areas, but the direction of causality remains to be determined. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Gait and Cognition: A Complementary Approach to Understanding Brain Function and the Risk of Falling

PubMed Central

Montero-Odasso, Manuel; Verghese, Joe; Beauchet, Olivier; Hausdorff, Jeffrey M.

2012-01-01

Until recently, clinicians and researchers have performed gait assessments and cognitive assessments separately when evaluating older adults. Increasing evidence from clinical practice, epidemiological studies, and clinical trials shows that gait and cognition are inter-related in older adults. Quantifiable alterations in gait among older adults are associated with falls, dementia, and disability. At the same time, emerging evidence indicates that early disturbances in cognitive processes such as attention, executive function, and working memory are associated with slower gait and gait instability during single and dual-task testing, and that these cognitive disturbances assist in the prediction of future mobility loss, falls, and progression to dementia. This paper reviews the importance of the gait-cognition inter-relationship in aging and presents evidence that gait assessments can provide a window into the understanding of cognitive function and dysfunctions, and fall risk in older people in clinical practice. To this end, the benefits of dual-task gait assessments (e.g., walking while performing an attention-demanding task) as a marker of fall risk are summarized. Further, we also present a potential complementary approach for reducing the risk of falls by improving certain aspects of cognition through both non-pharmacological and pharmacological treatments. Untangling the relationship between early gait disturbances and early cognitive changes may be helpful for identifying older adults at higher risk of experiencing mobility decline, falls and the progression to dementia. PMID:23110433

Unfolding dimension and the search for functional markers in the human electroencephalogram

NASA Astrophysics Data System (ADS)

Dünki, Rudolf M.; Schmid, Gary Bruno

1998-02-01

A biparametric approach to dimensional analysis in terms of a so-called ``unfolding dimension'' is introduced to explore the extent to which the human EEG can be described by stable features characteristic of an individual despite the well-known problems of intraindividual variability. Our analysis comprises an EEG data set recorded from healthy individuals over a time span of 5 years. The outcome is shown to be comparable to advanced linear methods of spectral analysis with regard to intraindividual specificity and stability over time. Such linear methods have not yet proven to be specific to the EEG of different brain states. Thus we have also investigated the specificity of our biparametric approach by comparing the mental states schizophrenic psychosis and remission, i.e., illness versus full recovery. A difference between EEG in psychosis and remission became apparent within recordings taken at rest with eyes closed and no stimulated or requested mental activity. Hence our approach distinguishes these functional brain states even in the absence of an active or intentional stimulus. This sheds a different light upon theories of schizophrenia as an information-processing disturbance of the brain.

[Music and neurology].

PubMed

Arias Gómez, M

2007-01-01

Music perception and output are special functions of the human brain. Investigation in this field is growing with the support of modern neuroimaging techniques (functional magnetic resonance imaging, positron emission tomography). Interest in the music phenomenon and the disorders regarding its processing has been limited. Music is not just an artistic activity but a language to communicate, evoke and reinforce several emotions. Although the subject is still under debate, processing of music is independent of common language and each one uses independent circuits. One may be seriously affected and the other practically unharmed. On the other hand, there may be separate channels within the processing of music for the temporary elements (rhythm), melodic elements (pitch, timbre, and melody), memory and emotional response. The study of subjects with absolute pitch, congenital and acquired amusias, musicogenic epilepsy and musical hallucinations has greatly contributed to the knowledge of how the brain processes music. Music training involves some changes in morphology and physiology of professional musicians' brains. Stress, chronic pain and professional dystonias constitute a special field of musicians' disturbances that concerns neurological practice. Listening to and playing music may have some educational and therapeutic benefits.

Suppression of miR-26a attenuates physiological disturbances arising from exposure of Nile tilapia (Oreochromis niloticus) to ammonia.

PubMed

Zhao, Yan; Zhou, Haotian; Ayisi, Christian Larbi; Wang, Yan; Wang, Jun; Chen, Xiaowu; Zhao, Jinling

2018-04-18

MicroRNAs may affect stress responses because they act as rapid responders at the post-translation level. In this study, we found that miR-26a is abundantly expressed in the brain and gill tissues of tilapia. Expression of miR-26a in the brain decreased significantly with increasing ammonia concentrations using stem-loop qPCR. To analyze the function of miRNA in vivo , miR-26a was stably knocked down with an antagomir in tilapia. Following ammonia challenge, miR-26a antagomir treatment significantly suppressed blood ammonia/[Cl - ]/[K + ] concentration and the reactive oxygen species production, while it markedly enhanced glutamine accumulation and antioxidant enzyme activity in the brain of tilapia, indicating that miR-26a may be involved in the remission of physiological disturbances resulting from ammonia stress. We strongly conclude that there is a direct link between miR-26a and the responses to ammonia in tilapia. Furthermore, bioinformatics analysis and luciferase assays demonstrated that miR-26a regulates HSP70 (heat shock protein 70) and GS (glutamine synthetase) expression by targeting their 3'-UTR and that the suppression of miR-26a could increase the intracellular level of HSP70 and GS in vivo . © 2018. Published by The Company of Biologists Ltd.

Neuropeptides and the social brain: potential rodent models of autism.

PubMed

Lim, Miranda M; Bielsky, Isadora F; Young, Larry J

2005-01-01

Conducting basic scientific research on a complex psychiatric disorder, such as autism, is a challenging prospect. It is difficult to dissociate the fundamental neurological and psychological processes that are disturbed in autism and, therefore, it is a challenge to discover accurate and reliable animal models of the disease. Because of their role in animal models of social processing and social bonding, the neuropeptides oxytocin and vasopressin are strong candidates for dysregulation in autism. In this review, we discuss the current animal models which have investigated oxytocin and vasopressin systems in the brain and their effects on social behavior. For example, mice lacking the oxytocin gene have profound deficits in social processing and social recognition, as do rats lacking vasopressin or mice lacking the vasopressin V1a receptor (V1aR). In another rodent model, monogamous prairie voles are highly social and form strong pair bonds with their mates. Pair bonds can be facilitated or disrupted by perturbing the oxytocin and vasopressin systems. Non-monogamous vole species that do not pair bond have different oxytocin and V1aR distribution patterns in the brain than monogamous vole species. Potential ties from these rodent models to the human autistic condition are then discussed. Given the hallmark disturbances in social function, the study of animal models of social behavior may provide novel therapeutic targets for the treatment of autism.

Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future “Non-Cognitive” Outcomes of Alzheimer’s Disease

PubMed Central

Ingber, Adam P.; Hassenstab, Jason; Fagan, Anne M.; Benzinger, Tammie L.S.; Grant, Elizabeth A.; Holtzman, David M.; Morris, John C.; Roe, Catherine M.

2016-01-01

Background The influence of reserve variables and Alzheimer’s disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on “non-cognitive” outcomes, including functional abilities and mood. Objective We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Methods Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Results Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. Conclusions The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD. PMID:27104893

Primary cortical folding in the human newborn: an early marker of later functional development.

PubMed

Dubois, J; Benders, M; Borradori-Tolsa, C; Cachia, A; Lazeyras, F; Ha-Vinh Leuchter, R; Sizonenko, S V; Warfield, S K; Mangin, J F; Hüppi, P S

2008-08-01

In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be present long before the appearance of functional symptoms. So far, the precise mechanisms responsible for such alteration in the convolution pattern during intra-uterine or post-natal development are still poorly understood. Here we compared anatomical and functional brain development in vivo among 45 premature newborns who experienced different intra-uterine environments: 22 normal singletons, 12 twins and 11 newborns with intrauterine growth restriction (IUGR). Using magnetic resonance imaging (MRI) and dedicated post-processing tools, we investigated early disturbances in cortical formation at birth, over the developmental period critical for the emergence of convolutions (26-36 weeks of gestational age), and defined early 'endophenotypes' of sulcal development. We demonstrated that twins have a delayed but harmonious maturation, with reduced surface and sulcation index compared to singletons, whereas the gyrification of IUGR newborns is discordant to the normal developmental trajectory, with a more pronounced reduction of surface in relation to the sulcation index compared to normal newborns. Furthermore, we showed that these structural measurements of the brain at birth are predictors of infants' outcome at term equivalent age, for MRI-based cerebral volumes and neurobehavioural development evaluated with the assessment of preterm infant's behaviour (APIB).

Volume transmission-mediated encephalopathies: a possible new concept?

PubMed

Hartung, Hans-Peter; Dihné, Marcel

2012-03-01

There is strong evidence that the composition of cerebrospinal fluid (CSF) influences brain development, neurogenesis, and behavior. The bidirectional exchange of CSF and interstitial fluid (ISF) across the ependymal and pia-glial membranes is required for these phenomena to occur. Because ISF surrounds the parenchymal compartment, neuroactive substances in the CSF and ISF can influence neuronal activity. Functionally important neuroactive substances are distributed to distant sites of the central nervous system by the convection and diffusion of CSF and ISF, a process known as volume transmission. It has recently been shown that pathologically altered CSF from patients with acute traumatic brain injury suppresses in vitro neuronal network activity (ivNNA) recorded by multielectrode arrays measuring synchronously bursting neural populations. Functionally relevant substances in pathologically altered CSF have been biochemically identified, and ivNNA has been partially recovered by pharmacologic intervention. It remains unclear whether the in vivo parenchymal compartment remains unaffected by pathologically altered CSF that significantly impairs ivNNA. We hypothesize that pathologic CSF alterations are not just passive indicators of brain diseases but that they actively and directly evoke functional disturbances in global brain activity through the distribution of neuroactive substances, for instance, secondary to focal neurologic disease. For this mechanism, we propose the new term volume transmission-mediated encephalopathies (VTE). Recording ivNNA in the presence of pure human CSF could help to identify and monitor functionally relevant CSF alterations that directly result in VTEs, and the collected data might point to therapeutic ways to antagonize these alterations.

Abnormality of circadian rhythm accompanied by an increase in frontal cortex serotonin in animal model of autism.

PubMed

Tsujino, Naohisa; Nakatani, Yasushi; Seki, Yoshinari; Nakasato, Akane; Nakamura, Michiko; Sugawara, Michiya; Arita, Hideho

2007-02-01

Several clinical reports have indicated that autistic patients often show disturbance of the circadian rhythm, which may be related to dysfunction of the serotonergic system in the brain. Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we examined locomotor activity and feeding under a reversed 12-h light/dark cycle, and found disturbance of the circadian rhythm characterized by frequent arousal during the light/sleep phase. In addition, measurement of brain serotonin (5-HT) level using in vivo microdialysis showed that the brain 5-HT level in VPA-exposed rats was significantly higher than that in control rats. These results suggest that a higher brain 5-HT level might be responsible for the irregular sleep/awake rhythm in autism.

Altered functional connectivity of amygdala underlying the neuromechanism of migraine pathogenesis.

PubMed

Chen, Zhiye; Chen, Xiaoyan; Liu, Mengqi; Dong, Zhao; Ma, Lin; Yu, Shengyuan

2017-12-01

The amygdala is a large grey matter complex in the limbic system, and it may contribute in the neurolimbic pain network in migraine. However, the detailed neuromechanism remained to be elucidated. The objective of this study is to investigate the amygdala structural and functional changes in migraine and to elucidate the mechanism of neurolimbic pain-modulating in the migraine pathogenesis. Conventional MRI, 3D structure images and resting state functional MRI were performed in 18 normal controls (NC), 18 patients with episodic migraine (EM), and 16 patients with chronic migraine (CM). The amygdala volume was measured using FreeSurfer software and the functional connectivity (FC) of bilateral amygdala was computed over the whole brain. Analysis of covariance was performed on the individual FC maps among groups. The increased FC of left amygdala was observed in EM compared with NC, and the decreased of right amygdala was revealed in CM compared with NC. The increased FC of bilateral amygdala was observed in CM compared with EM. The correlation analysis showed a negative correlation between the score of sleep quality (0, normal; 1, mild sleep disturbance; 2, moderate sleep disturbance; 3, serious sleep disturbance) and the increased FC strength of left amygdala in EM compared with NC, and a positive correlation between the score of sleep quality and the increased FC strength of left amygdala in CM compared with EM, and other clinical variables showed no significant correlation with altered FC of amygdala. The altered functional connectivity of amygdala demonstrated that neurolimbic pain network contribute in the EM pathogenesis and CM chronicization.

Functional brain networks in schizophrenia: a review.

PubMed

Calhoun, Vince D; Eichele, Tom; Pearlson, Godfrey

2009-01-01

Functional magnetic resonance imaging (fMRI) has become a major technique for studying cognitive function and its disruption in mental illness, including schizophrenia. The major proportion of imaging studies focused primarily upon identifying regions which hemodynamic response amplitudes covary with particular stimuli and differentiate between patient and control groups. In addition to such amplitude based comparisons, one can estimate temporal correlations and compute maps of functional connectivity between regions which include the variance associated with event-related responses as well as intrinsic fluctuations of hemodynamic activity. Functional connectivity maps can be computed by correlating all voxels with a seed region when a spatial prior is available. An alternative are multivariate decompositions such as independent component analysis (ICA) which extract multiple components, each of which is a spatially distinct map of voxels with a common time course. Recent work has shown that these networks are pervasive in relaxed resting and during task performance and hence provide robust measures of intact and disturbed brain activity. This in turn bears the prospect of yielding biomarkers for schizophrenia, which can be described both in terms of disrupted local processing as well as altered global connectivity between large-scale networks. In this review we will summarize functional connectivity measures with a focus upon work with ICA and discuss the meaning of intrinsic fluctuations. In addition, examples of how brain networks have been used for classification of disease will be shown. We present work with functional network connectivity, an approach that enables the evaluation of the interplay between multiple networks and how they are affected in disease. We conclude by discussing new variants of ICA for extracting maximally group discriminative networks from data. In summary, it is clear that identification of brain networks and their inter-relationships with fMRI has great potential to improve our understanding of schizophrenia.

No Escaping the Rat Race: Simulated Night Shift Work Alters the Time-of-Day Variation in BMAL1 Translational Activity in the Prefrontal Cortex.

PubMed

Marti, Andrea R; Patil, Sudarshan; Mrdalj, Jelena; Meerlo, Peter; Skrede, Silje; Pallesen, Ståle; Pedersen, Torhild T; Bramham, Clive R; Grønli, Janne

2017-01-01

Millions of people worldwide work during the night, resulting in disturbed circadian rhythms and sleep loss. This may cause deficits in cognitive functions, impaired alertness and increased risk of errors and accidents. Disturbed circadian rhythmicity resulting from night shift work could impair brain function and cognition through disrupted synthesis of proteins involved in synaptic plasticity and neuronal function. Recently, the circadian transcription factor brain-and-muscle arnt-like protein 1 (BMAL1) has been identified as a promoter of mRNA translation initiation, the most highly regulated step in protein synthesis, through binding to the mRNA "cap". In this study we investigated the effects of simulated shift work on protein synthesis markers. Male rats ( n = 40) were exposed to forced activity, either in their rest phase (simulated night shift work) or in their active phase (simulated day shift work) for 3 days. Following the third work shift, experimental animals and time-matched undisturbed controls were euthanized (rest work at ZT12; active work at ZT0). Tissue lysates from two brain regions (prefrontal cortex, PFC and hippocampus) implicated in cognition and sleep loss, were analyzed with m 7 GTP (cap) pull-down to examine time-of-day variation and effects of simulated shift work on cap-bound protein translation. The results show time-of-day variation of protein synthesis markers in PFC, with increased protein synthesis at ZT12. In the hippocampus there was little difference between ZT0 and ZT12. Active phase work did not induce statistically significant changes in protein synthesis markers at ZT0 compared to time-matched undisturbed controls. Rest work, however, resulted in distinct brain-region specific changes of protein synthesis markers compared to time-matched controls at ZT12. While no changes were observed in the hippocampus, phosphorylation of cap-bound BMAL1 and its regulator S6 kinase beta-1 (S6K1) was significantly reduced in the PFC, together with significant reduction in the synaptic plasticity associated protein activity-regulatedcytoskeleton-associated protein (Arc). Our results indicate considerable time-of-day and brain-region specific variation in cap-dependent translation initiation. We concludethat simulated night shift work in rats disrupts the pathways regulating the circadian component of the translation of mRNA in the PFC, and that this may partly explain impaired waking function during night shift work.

Sleep and Circadian Contributions to Adolescent Alcohol Use Disorder

PubMed Central

Hasler, Brant P.; Soehner, Adriane M.; Clark, Duncan B.

2014-01-01

Adolescence is a time of marked changes across sleep, circadian rhythms, brain function, and alcohol use. Starting at puberty, adolescents’ endogenous circadian rhythms and preferred sleep times shift later, often leading to a mismatch with the schedules imposed by secondary education. This mismatch induces circadian misalignment and sleep loss, which have been associated with affect dysregulation, increased drug and alcohol use, and other risk-taking behaviors in adolescents and adults. In parallel to developmental changes in sleep, adolescent brains are undergoing structural and functional changes in the circuits subserving the pursuit and processing of rewards. These developmental changes in reward processing likely contribute to the initiation of alcohol use during adolescence. Abundant evidence indicates that sleep and circadian rhythms modulate reward function, suggesting that adolescent sleep and circadian disturbance may contribute to altered reward function, and in turn, alcohol involvement. In this review, we summarize the relevant evidence and propose that these parallel developmental changes in sleep, circadian rhythms, and neural processing of reward interact to increase risk for alcohol use disorder (AUD). PMID:25442171

Neuroendocrine abnormalities in patients with traumatic brain injury

NASA Technical Reports Server (NTRS)

Yuan, X. Q.; Wade, C. E.

1991-01-01

This article provides an overview of hypothalamic and pituitary alterations in brain trauma, including the incidence of hypothalamic-pituitary damage, injury mechanisms, features of the hypothalamic-pituitary defects, and major hypothalamic-pituitary disturbances in brain trauma. While hypothalamic-pituitary lesions have been commonly described at postmortem examination, only a limited number of clinical cases of traumatic hypothalamic-pituitary dysfunction have been reported, probably because head injury of sufficient severity to cause hypothalamic and pituitary damage usually leads to early death. With the improvement in rescue measures, an increasing number of severely head-injured patients with hypothalamic-pituitary dysfunction will survive to be seen by clinicians. Patterns of endocrine abnormalities following brain trauma vary depending on whether the injury site is in the hypothalamus, the anterior or posterior pituitary, or the upper or lower portion of the pituitary stalk. Injury predominantly to the hypothalamus can produce dissociated ACTH-cortisol levels with no response to insulin-induced hypoglycemia and a limited or failed metopirone test, hypothyroxinemia with a preserved thyroid-stimulating hormone response to thyrotropin-releasing hormone, low gonadotropin levels with a normal response to gonadotropin-releasing hormone, a variable growth hormone (GH) level with a paradoxical rise in GH after glucose loading, hyperprolactinemia, the syndrome of inappropriate ADH secretion (SIADH), temporary or permanent diabetes insipidus (DI), disturbed glucose metabolism, and loss of body temperature control. Severe damage to the lower pituitary stalk or anterior lobe can cause low basal levels of all anterior pituitary hormones and eliminate responses to their releasing factors. Only a few cases showed typical features of hypothalamic or pituitary dysfunction. Most severe injuries are sufficient to damage both structures and produce a mixed endocrine picture. Increased intracranial pressure, which releases vasopressin by altering normal hypothalamic anatomy, may represent a unique type of stress to neuroendocrine systems and may contribute to adrenal secretion by a mechanism that requires intact brainstem function. Endocrine function should be monitored in brain-injured patients with basilar skull fractures and protracted posttraumatic amnesia, and patients with SIADH or DI should be closely monitored for other endocrine abnormalities.

Regional white matter lesions predict falls in patients with amnestic mild cognitive impairment and Alzheimer's disease.

PubMed

Ogama, Noriko; Sakurai, Takashi; Shimizu, Atsuya; Toba, Kenji

2014-01-01

Preventive strategy for falls in demented elderly is a clinical challenge. From early-stage of Alzheimer's disease (AD), patients show impaired balance and gait. The purpose of this study is to determine whether regional white matter lesions (WMLs) can predict balance/gait disturbance and falls in elderly with amnestic mild cognitive impairment (aMCI) or AD. Cross-sectional. Hospital out-patient clinic. One hundred sixty-three patients diagnosed with aMCI or AD were classified into groups having experienced falls (n = 63) or not (n = 100) in the previous year. Cognition, depression, behavior and psychological symptoms of dementia, medication, and balance/gait function were evaluated. Regional WMLs were visually analyzed as periventricular hyperintensity in frontal caps, bands, and occipital caps, and as deep white matter hyperintensity in frontal, parietal, temporal, and occipital lobes, basal ganglia, thalamus, and brain stem. Brain atrophy was linearly measured. The fallers had a greater volume of WMLs and their posture/gait performance tended to be worse than nonfallers. Several WMLs in particular brain regions were closely associated with balance and gait impairment. Besides polypharmacy, periventricular hyperintensity in frontal caps and occipital WMLs were strong predictors for falls, even after potential risk factors for falls were considered. Regional white matter burden, independent of cognitive decline, correlates with balance/gait disturbance and predicts falls in elderly with aMCI and AD. Careful insight into regional WMLs on brain magnetic resonance may greatly help to diagnose demented elderly with a higher risk of falls. Copyright © 2014 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

A cognitive neuroscience perspective on psychopathy: evidence for paralimbic system dysfunction.

PubMed

Kiehl, Kent A

2006-06-15

Psychopathy is a complex personality disorder that includes interpersonal and affective traits such as glibness, lack of empathy, guilt or remorse, shallow affect, and irresponsibility, and behavioral characteristics such as impulsivity, poor behavioral control, and promiscuity. Much is known about the assessment of psychopathy; however, relatively little is understood about the relevant brain disturbances. The present review integrates data from studies of behavioral and cognitive changes associated with focal brain lesions or insults and results from psychophysiology, cognitive psychology and cognitive and affective neuroscience in health and psychopathy. The review illustrates that the brain regions implicated in psychopathy include the orbital frontal cortex, insula, anterior and posterior cingulate, amygdala, parahippocampal gyrus, and anterior superior temporal gyrus. The relevant functional neuroanatomy of psychopathy thus includes limbic and paralimbic structures that may be collectively termed 'the paralimbic system'. The paralimbic system dysfunction model of psychopathy is discussed as it relates to the extant literature on psychopathy.

[Clinical feature of ALS with communication disturbance; the possibility to communicate in TLS].

PubMed

Nagao, Masahiro

2013-01-01

In the subsets of amyotrohic lateral sclerosis (ALS), totally-locked in state (TLS) is shown as the result of marked progression of motor neuron degeneration. In TLS, patients are impossible to move any voluntary muscles. As the result, patients with TLS cannot communicate with any augmentative and alternative communication devices(AACD) at present. To find the AACD that enables for TLS to communicate, we examined the clinical character, brain MRI, SPECT and evoked potentials in TLS. Brain MRI showed marked brain atrophy including the brainstem, but the occipital lobe was spared. SPECT and visual evoked potentials (VEP) showed preserved physiological function of the occipital lobe in TLS. The results suggest that neuronal degeneration in TLS is not restricted to motor system, but that the visual pathways are spared. Patients with TLS may be possible to use AACD that utilize the visual pathway.

Abnormal functional connectivity of hippocampus during episodic memory retrieval processing network in amnestic mild cognitive impairment.

PubMed

Bai, Feng; Zhang, Zhijun; Watson, David R; Yu, Hui; Shi, Yongmei; Yuan, Yonggui; Zang, Yufeng; Zhu, Chaozhe; Qian, Yun

2009-06-01

Functional connectivity magnetic resonance imaging technique has revealed the importance of distributed network structures in higher cognitive processes in the human brain. The hippocampus has a key role in a distributed network supporting memory encoding and retrieval. Hippocampal dysfunction is a recurrent finding in memory disorders of aging such as amnestic mild cognitive impairment (aMCI) in which learning- and memory-related cognitive abilities are the predominant impairment. The functional connectivity method provides a novel approach in our attempts to better understand the changes occurring in this structure in aMCI patients. Functional connectivity analysis was used to examine episodic memory retrieval networks in vivo in twenty 28 aMCI patients and 23 well-matched control subjects, specifically between the hippocampal structures and other brain regions. Compared with control subjects, aMCI patients showed significantly lower hippocampus functional connectivity in a network involving prefrontal lobe, temporal lobe, parietal lobe, and cerebellum, and higher functional connectivity to more diffuse areas of the brain than normal aging control subjects. In addition, those regions associated with increased functional connectivity with the hippocampus demonstrated a significantly negative correlation to episodic memory performance. aMCI patients displayed altered patterns of functional connectivity during memory retrieval. The degree of this disturbance appears to be related to level of impairment of processes involved in memory function. Because aMCI is a putative prodromal syndrome to Alzheimer's disease (AD), these early changes in functional connectivity involving the hippocampus may yield important new data to predict whether a patient will eventually develop AD.

Lateralization of Egocentric and Allocentric Spatial Processing after Parietal Brain Lesions

ERIC Educational Resources Information Center

Iachini, Tina; Ruggiero, Gennaro; Conson, Massimiliano; Trojano, Luigi

2009-01-01

The purpose of this paper was to verify whether left and right parietal brain lesions may selectively impair egocentric and allocentric processing of spatial information in near/far spaces. Two Right-Brain-Damaged (RBD), 2 Left-Brain-Damaged (LBD) patients (not affected by neglect or language disturbances) and eight normal controls were submitted…

Effets des radiofréquences sur le système nerveux central chez lʼhomme : EEG, sommeil, cognition, vascularisation

NASA Astrophysics Data System (ADS)

Ghosn, Rania; Villégier, Anne-Sophie; Selmaoui, Brahim; Thuróczy, Georges; de Sèze, René

2013-05-01

Most of clinical studies on radiofrequency electromagnetic fields (RF) were directed at mobile phone-related exposures, usually at the level of the head, at their effect on some physiological functions including sleep, brain electrical activity (EEG), cognitive processes, brain vascularisation, and more generally on the cardiovascular and endocrine systems. They were frequently carried out on healthy adults. Effects on the amplitude of EEG alpha waves, mainly during sleep, look reproducible. It would however be important to define more precisely whether and how the absence of electromagnetic disturbance between RF exposure and the recording systems is checked. No consensus arises about cognitive effects. Some effects on cerebral vascularisation need complementary work.

Correlation changes in EEG, conditioned and behavioral reactions with various degrees of oxygen insufficiency

NASA Technical Reports Server (NTRS)

Agadzhanyan, N. A.; Zakharova, I. N.; Kalyuzhnyy, L. V.; Dvorzhak, I. I.; Moravek, M.; Tsmiral, Y. I.

1974-01-01

The dynamics of change in bioelectric activity of the brain during acute hypoxia are studied for the time that working capacity and active consciousness are preserved, and to establish the correlation between EEG changes and behavioral reactions under oxygen starvation. Changes in body functions and behavioral disturbances are related to the degree of oxygen saturation in the blood, to bioelectric activity of the brain, and to an increase in conditioned reflexes. The capacity for adequate reaction to external signals and for coordinated psychomotor activity after loss of consciousness returns to man after 30 seconds. Repeated effects of hypoxia produce changes in the physiological reactions of the body directed toward better adaptation to changing gaseous environments.

Circadian Rhythm Disturbances in Mood Disorders: Insights into the Role of the Suprachiasmatic Nucleus

PubMed Central

2017-01-01

Circadian rhythm disturbances are a common symptom among individuals with mood disorders. The suprachiasmatic nucleus (SCN), in the ventral part of the anterior hypothalamus, orchestrates physiological and behavioral circadian rhythms. The SCN consists of self-sustaining oscillators and receives photic and nonphotic cues, which entrain the SCN to the external environment. In turn, through synaptic and hormonal mechanisms, the SCN can drive and synchronize circadian rhythms in extra-SCN brain regions and peripheral tissues. Thus, genetic or environmental perturbations of SCN rhythms could disrupt brain regions more closely related to mood regulation and cause mood disturbances. Here, we review clinical and preclinical studies that provide evidence both for and against a causal role for the SCN in mood disorders. PMID:29230328

Disturbed oxidative metabolism in organic brain syndrome caused by bismuth in skin creams.

PubMed

Krüger, G; Thomas, D J; Weinhardt, F; Hoyer, S

1976-09-04

Two patients are described with an organic brain syndrome thought to be due to bismuth (Bi) absorbed from a skin cream. Both patients had intellectual impairment and memory loss punctuated by periods of confusion, tremulousness, clumsiness, difficulty in walking, and myoclonic jerks. A similar clinical picture has been reported from Australia and France in patients taking insoluble bismuth salts by mouth. Bi was found in cerebral venous blood in both patients and in the cerebrospinal fluid in one. It is suggested that bismuth can cross the blood/brain barrier and disturb oxidative cerebral metabolism, because increased lactate production was found with decreased consumption of oxygen and glucose and lowered cerebral blood-flow.

Sleep Disturbances in Adolescents with ADHD: A Systematic Review and Framework for Future Research

PubMed Central

Lunsford-Avery, Jessica R.; Krystal, Andrew D.; Kollins, Scott H.

2016-01-01

Background Biological mechanisms underlying symptom and prognostic heterogeneity in Attention-Deficit/Hyperactivity Disorder (ADHD) are unclear. Sleep impacts neurocognition and daytime functioning and is disrupted in ADHD, yet little is known about sleep in ADHD during adolescence, a period characterized by alterations in sleep, brain structure, and environmental demands as well as diverging ADHD trajectories. Methods A systematic review identified studies published prior to August 2016 assessing sleep in adolescents (aged 10–19 years) with ADHD or participating in population-based studies measuring ADHD symptoms. Results Twenty-five studies were identified (19 subjective report, 6 using actigraphy/polysomnography). Findings are mixed but overall suggest associations between sleep disturbances and 1) ADHD symptoms in the population and 2) poorer clinical, neurocognitive, and functional outcomes among adolescents with ADHD. Common limitations of studies included small or non-representative samples, non-standardized sleep measures, and cross-sectional methodology. Conclusions Current data on sleep in adolescent ADHD are sparse and limited by methodological concerns. Future studies are critical for clarifying a potential role of sleep in contributing to heterogeneity of ADHD presentation and prognosis. Potential mechanisms by which sleep disturbances during adolescence may contribute to worsened symptom severity and persistence of ADHD into adulthood and an agenda to guide future research are discussed. PMID:27969004

Modelling verbal aggression, physical aggression and inappropriate sexual behaviour after acquired brain injury

PubMed Central

James, Andrew I. W.; Böhnke, Jan R.; Young, Andrew W.; Lewis, Gary J.

2015-01-01

Understanding the underpinnings of behavioural disturbances following brain injury is of considerable importance, but little at present is known about the relationships between different types of behavioural disturbances. Here, we take a novel approach to this issue by using confirmatory factor analysis to elucidate the architecture of verbal aggression, physical aggression and inappropriate sexual behaviour using systematic records made across an eight-week observation period for a large sample (n = 301) of individuals with a range of brain injuries. This approach offers a powerful test of the architecture of these behavioural disturbances by testing the fit between observed behaviours and different theoretical models. We chose models that reflected alternative theoretical perspectives based on generalized disinhibition (Model 1), a difference between aggression and inappropriate sexual behaviour (Model 2), or on the idea that verbal aggression, physical aggression and inappropriate sexual behaviour reflect broadly distinct but correlated clinical phenomena (Model 3). Model 3 provided the best fit to the data indicating that these behaviours can be viewed as distinct, but with substantial overlap. These data are important both for developing models concerning the architecture of behaviour as well as for clinical management in individuals with brain injury. PMID:26136449

Interactions of Circadian Rhythmicity, Stress and Orexigenic Neuropeptide Systems: Implications for Food Intake Control.

PubMed

Blasiak, Anna; Gundlach, Andrew L; Hess, Grzegorz; Lewandowski, Marian H

2017-01-01

Many physiological processes fluctuate throughout the day/night and daily fluctuations are observed in brain and peripheral levels of several hormones, neuropeptides and transmitters. In turn, mediators under the "control" of the "master biological clock" reciprocally influence its function. Dysregulation in the rhythmicity of hormone release as well as hormone receptor sensitivity and availability in different tissues, is a common risk-factor for multiple clinical conditions, including psychiatric and metabolic disorders. At the same time circadian rhythms remain in a strong, reciprocal interaction with the hypothalamic-pituitary-adrenal (HPA) axis. Recent findings point to a role of circadian disturbances and excessive stress in the development of obesity and related food consumption and metabolism abnormalities, which constitute a major health problem worldwide. Appetite, food intake and energy balance are under the influence of several brain neuropeptides, including the orexigenic agouti-related peptide, neuropeptide Y, orexin, melanin-concentrating hormone and relaxin-3. Importantly, orexigenic neuropeptide neurons remain under the control of the circadian timing system and are highly sensitive to various stressors, therefore the potential neuronal mechanisms through which disturbances in the daily rhythmicity and stress-related mediator levels contribute to food intake abnormalities rely on reciprocal interactions between these elements.

Neurobehavioral and self-awareness changes after traumatic brain injury: Towards new multidimensional approaches.

PubMed

Arnould, A; Dromer, E; Rochat, L; Van der Linden, M; Azouvi, P

2016-02-01

Neurobehavioral and self-awareness changes are frequently observed following traumatic brain injury (TBI). These disturbances have been related to negative consequences on functional outcomes, caregiver distress and social reintegration, representing therefore a challenge for clinical research. Some studies have recently been conducted to specifically explore apathetic and impulsive manifestations, as well as self-awareness impairments in patients with TBI. These findings underlined the heterogeneity of clinical manifestations for each behavioral disturbance and the diversity of psychological processes involved. In this context, new multidimensional approaches taking into account the various processes at play have been proposed to better understand and apprehend the complexity and dynamic nature of these problematic behaviors. In addition, the involvement of social and environmental factors as well as premorbid personality traits have increasingly been addressed. These new multidimensional frameworks have the potential to ensure targeted and effective rehabilitation by allowing a better identification and therefore consideration of the various mechanisms involved in the onset of problematic behaviors. In this context, the main objective of this position paper was to demonstrate the interest of multidimensional approaches in the understanding and rehabilitation of problematic behaviors in patients with TBI. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Combining neuropsychological and cognitive-behavioral approaches for treating psychological sequelae of acquired brain injury.

PubMed

Doering, Bettina; Exner, Cornelia

2011-03-01

Acquired brain injury (ABI) does not only result in physical and cognitive impairments, but may also entail behavioral-emotional difficulties and mental disorders. Although neuropsychological approaches target the rehabilitation of cognitive deficits, the treatment of emotional and behavioral sequelae has received less consideration. This review argues for the integration of cognitive-behavioral approaches into the rehabilitation process and examines respective recent research. Cognitive-behavioral interventions have been investigated in the treatment of behavioral disturbances and mental disorders after ABI. They have also been targeted at supporting adaptive coping with chronic injury-related impairments. Problem-solving approaches of cognitive behavioral therapy may work as meta-models or framework for the rehabilitative process. Unfortunately, most studies reviewed employed methodologically weak designs, which limit convincing conclusions. Still, positive intervention effects have been demonstrated concerning specific outcome measures. Whether these changes also translate into increased psychosocial functioning or quality of life remains unclear. Methodologically sound evidence for cognitive-behavioral interventions after ABI is limited, but preliminary results support the effectiveness of these interventions in the treatment of behavioral disorders and emotional disturbances after ABI. Integrating neuropsychological and cognitive-behavioral approaches may therefore prove beneficial to the rehabilitation process.

Role of maternal thyroid hormones in the developing neocortex and during human evolution

PubMed Central

Stenzel, Denise; Huttner, Wieland B.

2013-01-01

The importance of thyroid hormones during brain development has been appreciated for many decades. In humans, low levels of circulating maternal thyroid hormones, e.g., caused by maternal hypothyroidism or lack of iodine in diet, results in a wide spectrum of severe neurological defects, including neurological cretinism characterized by profound neurologic impairment and mental retardation, underlining the importance of the maternal thyroid hormone contribution. In fact, iodine intake, which is essential for thyroid hormone production in the thyroid gland, has been related to the expansion of the brain, associated with the increased cognitive capacities during human evolution. Because thyroid hormones regulate transcriptional activity of target genes via their nuclear thyroid hormone receptors (THRs), even mild and transient changes in maternal thyroid hormone levels can directly affect and alter the gene expression profile, and thus disturb fetal brain development. Here we summarize how thyroid hormones may have influenced human brain evolution through the adaptation to new habitats, concomitant with changes in diet and, therefore, iodine intake. Further, we review the current picture we gained from experimental studies in rodents on the function of maternal thyroid hormones during developmental neurogenesis. We aim to evaluate the effects of maternal thyroid hormone deficiency as well as lack of THRs and transporters on brain development and function, shedding light on the cellular behavior conducted by thyroid hormones. PMID:23882187

Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer's disease.

PubMed

Agrawal, Mukta; Ajazuddin; Tripathi, Dulal K; Saraf, Swarnlata; Saraf, Shailendra; Antimisiaris, Sophia G; Mourtas, Spyridon; Hammarlund-Udenaes, Margareta; Alexander, Amit

2017-08-28

In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli. This functionally essential structure creates a major hurdle for delivery of any drug into the brain. Still, there are some provisions on BBB which facilitate the entry of useful substances in the brain via specific mechanisms like passive diffusion, receptor-mediated transcytosis, carrier-mediated transcytosis etc. Another important factor for drug transport is the selection of a suitable drug delivery systems like, liposome, which is a novel drug carrier system offering a potential approach to resolving this problem. Its unique phospholipid bilayer structure (similar to physiological membrane) had made it more compatible with the lipoidal layer of BBB and helps the drug to enter the brain. The present review work focused on various surface modifications with functional ligand (like lactoferrin, transferrin etc.) and carrier molecules (such as glutathione, glucose etc.) on the liposomal structure to enhance its brain targeting ability towards the successful treatment of Alzheimer disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinically relevant genetic biomarkers from the brain in alcoholism with representation on high resolution chromosome ideograms.

PubMed

Manzardo, Ann M; McGuire, Austen; Butler, Merlin G

2015-04-15

Alcoholism arises from combined effects of multiple biological factors including genetic and non-genetic causes with gene/environmental interaction. Intensive research and advanced genetic technology has generated a long list of genes and biomarkers involved in alcoholism neuropathology. These markers reflect complex overlapping and competing effects of possibly hundreds of genes which impact brain structure, function, biochemical alcohol processing, sensitivity and risk for dependence. We compiled a tabular list of clinically relevant genetic biomarkers for alcoholism targeting expression disturbances in the human brain through an extensive search of keywords related to alcoholism, alcohol abuse, and genetics from peer reviewed medical research articles and related nationally sponsored websites. Gene symbols were then placed on high resolution human chromosome ideograms with gene descriptions in tabular form. We identified 337 clinically relevant genetic biomarkers and candidate genes for alcoholism and alcohol-responsiveness from human brain research. Genetic biomarkers included neurotransmitter pathways associated with brain reward processes for dopaminergic (e.g., DRD2, MAOA, and COMT), serotoninergic (e.g., HTR3A, HTR1B, HTR3B, and SLC6A4), GABAergic (e.g., GABRA1, GABRA2, and GABRG1), glutaminergic (GAD1, GRIK3, and GRIN2C) and opioid (e.g., OPRM1, OPRD1, and OPRK1) pathways which presumably impact reinforcing properties of alcohol. Gene level disturbances in cellular and molecular networks impacted by alcohol and alcoholism pathology include transketolase (TKT), transferrin (TF), and myelin (e.g., MBP, MOBP, and MOG). High resolution chromosome ideograms provide investigators, physicians, geneticists and counselors a convenient visual image of the distribution of alcoholism genetic biomarkers from brain research with alphabetical listing of genes in tabular form allowing comparison between alcoholism-related phenotypes, and clinically-relevant alcoholism gene(s) at the chromosome band level to guide research, diagnosis, and treatment. Chromosome ideograms may facilitate gene-based personalized counseling of alcohol dependent individuals and their families. Copyright © 2015 Elsevier B.V. All rights reserved.

Brain perfusion abnormalities in Rett syndrome: a qualitative and quantitative SPET study with 99Tc(m)-ECD.

PubMed

Burroni, L; Aucone, A M; Volterrani, D; Hayek, Y; Bertelli, P; Vella, A; Zappella, M; Vattimo, A

1997-06-01

Rett syndrome is a progressive neurological paediatric disorder associated with severe mental deficiency, which affects only girls. The aim of this study was to determine if brain blood flow abnormalities detected with 99Tc(m)-ethyl-cysteinate-dimer (99Tc[m]-ECD) single photon emission tomography (SPET) can explain the clinical manifestation and progression of the disease. Qualitative and quantitative global and regional brain blood flow was evaluated in 12 girls with Rett syndrome and compared with an aged-matched reference group of children. In comparison with the reference group, SPET revealed a considerable global reduction in cerebral perfusion in the groups of girls with Rett syndrome. A large statistical difference was noted, which was more evident when comparing the control group with girls with stage IV Rett syndrome than girls with stage III Rett syndrome. The reduction in cerebral perfusion reflects functional disturbance in the brain of children with Rett syndrome. These data confirm that 99Tc(m)-ECD brain SPET is sensitive in detecting hypoperfused areas in girls with Rett syndrome that may be associated with brain atrophy, even when magnetic resonance imaging appears normal.

Quantitative complexity analysis in multi-channel intracranial EEG recordings form epilepsy brains

PubMed Central

Liu, Chang-Chia; Pardalos, Panos M.; Chaovalitwongse, W. Art; Shiau, Deng-Shan; Ghacibeh, Georges; Suharitdamrong, Wichai; Sackellares, J. Chris

2008-01-01

Epilepsy is a brain disorder characterized clinically by temporary but recurrent disturbances of brain function that may or may not be associated with destruction or loss of consciousness and abnormal behavior. Human brain is composed of more than 10 to the power 10 neurons, each of which receives electrical impulses known as action potentials from others neurons via synapses and sends electrical impulses via a sing output line to a similar (the axon) number of neurons. When neuronal networks are active, they produced a change in voltage potential, which can be captured by an electroencephalogram (EEG). The EEG recordings represent the time series that match up to neurological activity as a function of time. By analyzing the EEG recordings, we sought to evaluate the degree of underlining dynamical complexity prior to progression of seizure onset. Through the utilization of the dynamical measurements, it is possible to classify the state of the brain according to the underlying dynamical properties of EEG recordings. The results from two patients with temporal lobe epilepsy (TLE), the degree of complexity start converging to lower value prior to the epileptic seizures was observed from epileptic regions as well as non-epileptic regions. The dynamical measurements appear to reflect the changes of EEG’s dynamical structure. We suggest that the nonlinear dynamical analysis can provide a useful information for detecting relative changes in brain dynamics, which cannot be detected by conventional linear analysis. PMID:19079790

[Emotion and basal ganglia (II): what can we learn from subthalamic nucleus deep brain stimulation in Parkinson's disease?].

PubMed

Péron, J; Dondaine, T

2012-01-01

The subthalamic nucleus deep-brain stimulation Parkinson's disease patient model seems to represent a unique opportunity for studying the functional role of the basal ganglia and notably the subthalamic nucleus in human emotional processing. Indeed, in addition to constituting a therapeutic advance for severely disabled Parkinson's disease patients, deep brain stimulation is a technique, which selectively modulates the activity of focal structures targeted by surgery. There is growing evidence of a link between emotional impairments and deep-brain stimulation of the subthalamic nucleus. In this context, according to the definition of emotional processing exposed in the companion paper available in this issue, the aim of the present review will consist in providing a synopsis of the studies that investigated the emotional disturbances observed in subthalamic nucleus deep brain stimulation Parkinson's disease patients. This review leads to the conclusion that several emotional components would be disrupted after subthalamic nucleus deep brain stimulation in Parkinson's disease: subjective feeling, neurophysiological activation, and motor expression. Finally, after a description of the limitations of this study model, we discuss the functional role of the subthalamic nucleus (and the striato-thalamo-cortical circuits in which it is involved) in emotional processing. It seems reasonable to conclude that the striato-thalamo-cortical circuits are indeed involved in emotional processing and that the subthalamic nucleus plays a central in role the human emotional architecture. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Functional brain correlates of heterosexual paedophilia.

PubMed

Schiffer, Boris; Paul, Thomas; Gizewski, Elke; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Kruger, Tillmann H C

2008-05-15

Although the neuronal mechanisms underlying normal sexual motivation and function have recently been examined, the alterations in brain function in deviant sexual behaviours such as paedophilia are largely unknown. The objective of this study was to identify paedophilia-specific functional networks implicated in sexual arousal. Therefore a consecutive sample of eight paedophile forensic inpatients, exclusively attracted to females, and 12 healthy age-matched heterosexual control participants from a comparable socioeconomic stratum participated in a visual sexual stimulation procedure during functional magnetic resonance imaging. The visual stimuli were sexually stimulating photographs and emotionally neutral photographs. Immediately after the imaging session subjective responses pertaining to sexual desire were recorded. Principally, the brain response of heterosexual paedophiles to heteropaedophilic stimuli was comparable to that of heterosexual males to heterosexual stimuli, including different limbic structures (amygdala, cingulate gyrus, and hippocampus), the substantia nigra, caudate nucleus, as well as the anterior cingulate cortex, different thalamic nuclei, and associative cortices. However, responses to visual sexual stimulation were found in the orbitofrontal cortex in healthy heterosexual males, but not in paedophiles, in whom abnormal activity in the dorsolateral prefrontal cortex was observed. Thus, in line with clinical observations and neuropsychological studies, it seems that central processing of sexual stimuli in heterosexual paedophiles may be altered by a disturbance in the prefrontal networks, which, as has already been hypothesized, may be associated with stimulus-controlled behaviours, such as sexual compulsive behaviours. Moreover, these findings may suggest a dysfunction (in the functional and effective connectivity) at the cognitive stage of sexual arousal processing.

Abnormal functional global and local brain connectivity in female patients with anorexia nervosa

PubMed Central

Geisler, Daniel; Borchardt, Viola; Lord, Anton R.; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A.; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

2016-01-01

Background Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. Methods To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Results Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. Limitations The present results may be limited to the methods applied during preprocessing and network construction. Conclusion We demonstrated anorexia nervosa–related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger. PMID:26252451

Abnormal functional global and local brain connectivity in female patients with anorexia nervosa.

PubMed

Geisler, Daniel; Borchardt, Viola; Lord, Anton R; Boehm, Ilka; Ritschel, Franziska; Zwipp, Johannes; Clas, Sabine; King, Joseph A; Wolff-Stephan, Silvia; Roessner, Veit; Walter, Martin; Ehrlich, Stefan

2016-01-01

Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. The present results may be limited to the methods applied during preprocessing and network construction. We demonstrated anorexia nervosa-related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger.

Cognitive impairment, clinical severity and MRI changes in MELAS syndrome.

PubMed

Kraya, Torsten; Neumann, Lena; Paelecke-Habermann, Yvonne; Deschauer, Marcus; Stoevesandt, Dietrich; Zierz, Stephan; Watzke, Stefan

2017-12-29

To examine clinical severity, cognitive impairment, and MRI changes in patients with MELAS syndrome. Cognitive-mnestic functions, brain MRI (lesion load, cella media index) and clinical severity of ten patients with MELAS syndrome were examined. All patients carried the m.3243A>G mutation. The detailed neuropsychological assessment revealed cognitive deficits in attention, executive function, visuoperception, and -construction. There were significant correlations between these cognitive changes, lesion load in MRI, disturbances in everyday life (clinical scale), and high scores in NMDAS. Patients with MELAS syndrome showed no global neuropsychological deficit, but rather distinct cognitive deficits. Copyright © 2018 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Correlation between white matter microstructure and executive functions suggests early developmental influence on long fibre tracts in preterm born adolescents.

PubMed

Vollmer, Brigitte; Lundequist, Aiko; Mårtensson, Gustaf; Nagy, Zoltan; Lagercrantz, Hugo; Smedler, Ann-Charlotte; Forssberg, Hans

2017-01-01

Executive functions are frequently a weakness in children born preterm. We examined associations of executive functions and general cognitive abilities with brain structure in preterm born adolescents who were born with appropriate weight for gestational age and who have no radiological signs of preterm brain injury on neuroimaging. The Stockholm Neonatal Project (SNP) is a longitudinal, population-based study of children born preterm (<36 weeks of gestation) with very low birth weight (<1501g) between 1988-1993. At age 18 years (mean 18 years, SD 2 weeks) 134 preterm born and 94 full term participants underwent psychological assessment (general intelligence, executive function measures). Of these, 71 preterm and 63 full term participants underwent Magnetic Resonance Imaging (MRI) at mean 15.2 years (range 12-18 years), including 3D T1-weighted images for volumetric analyses and Diffusion Tensor Imaging (DTI) for assessment of white matter microstructure. Group comparisons of regional grey and white matter volumes and fractional anisotropy (FA, as a measure of white matter microstructure) and, within each group, correlation analyses of cognitive measures with MRI metrics were carried out. Significant differences in grey and white matter regional volumes and widespread differences in FA were seen between the two groups. No significant correlations were found between cognitive measures and brain volumes in any group after correction for multiple comparisons. However, there were significant correlations between FA in projection fibres and long association fibres, linking frontal, temporal, parietal, and occipital lobes, and measures of executive function and general cognitive abilities in the preterm born adolescents, but not in the term born adolescents. In persons born preterm, in the absence of perinatal brain injury on visual inspection of MRI, widespread alterations in regional brain tissue volumes and microstructure are present in adolescence/young adulthood. Importantly, these alterations in WM tracts are correlated with measures of executive function and general cognitive abilities. Our findings suggest that disturbance of neural pathways, rather than changes in regional brain volumes, are involved in the impaired cognitive functions.

Abnormal activation of the social brain during face perception in autism.

PubMed

Hadjikhani, Nouchine; Joseph, Robert M; Snyder, Josh; Tager-Flusberg, Helen

2007-05-01

ASD involves a fundamental impairment in processing social-communicative information from faces. Several recent studies have challenged earlier findings that individuals with autism spectrum disorder (ASD) have no activation of the fusiform gyrus (fusiform face area, FFA) when viewing faces. In this study, we examined activation to faces in the broader network of face-processing modules that comprise what is known as the social brain. Using 3T functional resonance imaging, we measured BOLD signal changes in 10 ASD subjects and 7 healthy controls passively viewing nonemotional faces. We replicated our original findings of significant activation of face identity-processing areas (FFA and inferior occipital gyrus, IOG) in ASD. However, in addition, we identified hypoactivation in a more widely distributed network of brain areas involved in face processing [including the right amygdala, inferior frontal cortex (IFC), superior temporal sulcus (STS), and face-related somatosensory and premotor cortex]. In ASD, we found functional correlations between a subgroup of areas in the social brain that belong to the mirror neuron system (IFC, STS) and other face-processing areas. The severity of the social symptoms measured by the Autism Diagnostic Observation Schedule was correlated with the right IFC cortical thickness and with functional activation in that area. When viewing faces, adults with ASD show atypical patterns of activation in regions forming the broader face-processing network and social brain, outside the core FFA and IOG regions. These patterns suggest that areas belonging to the mirror neuron system are involved in the face-processing disturbances in ASD.

[The cognitive effects of ecstasy].

PubMed

Pázmány, Péter; Petschner, Péter; Ádori, Csaba; Kirilly, Eszter; Andó, Dénes Rómeó; Balogh, Brigitta; Gyöngyösi, Norbert; Bagdy, György

2013-12-01

The recreational drug ecstasy is widely used among dance clubbers for its acute euphoric and entactogenic effects. Ecstasy exerts its acute effects by increasing the extracellular concentration of monoamines in the brain by reversing the functions of reuptake mechanisms. These elevations in extracellular monoamine concentrations result in wake promoting effects, body hyperthermia and reductions in local cerebral blood flow. However, on the long-run, ecstasy reduces serotonin concentration and density of serotonergic markers in several brain areas. Functional deficits, like sleep disturbances, anxiogenic- and aggressive behavioral responses and mood disorders also may occur. However, one of the most prominent adverse effects is related to the cognitive functions. Following ecstasy use attenuated retro- and prospective memory and defective higher order cognitive functions can be observed, especially in heavy users. Several studies indicated the involvement of the endocannabinoid system, the sleep regulating centers and the hypothalamic-pituitary-adrenal axis based on or parallel to serotonergic damage in these processes. Recent evidence, however, also showed that changes in one of the latter systems can influence the functions of each other. In this review we summarize the related literature, and propose a complex mechanism for the long-lasting cognitive deficits following heavy ecstasy use.

Possible Effects of Synaptic Imbalances on Oligodendrocyte–Axonic Interactions in Schizophrenia: A Hypothetical Model

PubMed Central

Mitterauer, Bernhard J.; Kofler-Westergren, Birgitta

2011-01-01

A model of glial–neuronal interactions is proposed that could be explanatory for the demyelination identified in brains with schizophrenia. It is based on two hypotheses: (1) that glia–neuron systems are functionally viable and important for normal brain function, and (2) that disruption of this postulated function disturbs the glial categorization function, as shown by formal analysis. According to this model, in schizophrenia receptors on astrocytes in glial–neuronal synaptic units are not functional, loosing their modulatory influence on synaptic neurotransmission. Hence, an unconstrained neurotransmission flux occurs that hyperactivates the axon and floods the cognate receptors of neurotransmitters on oligodendrocytes. The excess of neurotransmitters may have a toxic effect on oligodendrocytes and myelin, causing demyelination. In parallel, an increasing impairment of axons may disconnect neuronal networks. It is formally shown how oligodendrocytes normally categorize axonic information processing via their processes. Demyelination decomposes the oligodendrocyte–axonic system making it incapable to generate categories of information. This incoherence may be responsible for symptoms of disorganization in schizophrenia, such as thought disorder, inappropriate affect and incommunicable motor behavior. In parallel, the loss of oligodendrocytes affects gap junctions in the panglial syncytium, presumably responsible for memory impairment in schizophrenia. PMID:21647404

The neurobiology of social environmental risk for schizophrenia: an evolving research field.

PubMed

Akdeniz, Ceren; Tost, Heike; Meyer-Lindenberg, Andreas

2014-04-01

Schizophrenia is a severe and complex brain disorder that usually manifests in early adulthood and disturbs a wide range of human functions. More than 100 years after its initial description, the pathophysiology of the disorder is still incompletely understood. Many epidemiological studies strongly suggest a complex interaction between genetic and environmental risk factors for the development of the disorder. While there is considerable evidence for a social environmental component of this risk, the links between adverse social factors and altered brain function have just come into focus. In the present review, we first summarize epidemiological evidence for the significance of social environmental risk factors, outline the role of altered social stress processing in mental illness, and review the latest experimental evidence for the neural correlates of social environmental risk for schizophrenia. The studies we have discussed in this review provide a selection of the current work in the field. We suggest that many of the social environmental risk factors may impact on perceived social stress and engage neural circuits in the brain whose functional and structural architecture undergoes detrimental change in response to prolonged exposure. We conclude that multidisciplinary approaches involving various fields and thoroughly constructed longitudinal designs are necessary to capture complex structure of social environmental risks.

Effects of Bisphenol A on glucose homeostasis and brain insulin signaling pathways in male mice.

PubMed

Fang, Fangfang; Chen, Donglong; Yu, Pan; Qian, Wenyi; Zhou, Jing; Liu, Jingli; Gao, Rong; Wang, Jun; Xiao, Hang

2015-02-01

The potential effects of Bisphenol A (BPA) on peripheral insulin resistance have recently gained more attention, however, its functions on brain insulin resistance are still unknown. The aim of the present study was to investigate the effects of BPA on insulin signaling and glucose transport in mouse brain. The male mice were administrated of 100 μg/kg/day BPA or vehicle for 15 days then challenged with glucose and insulin tolerance tests. The insulin levels were detected with radioimmunoassay (RIA), and the insulin signaling pathways were investigated by Western blot. Our results revealed that BPA significantly increased peripheral plasma insulin levels, and decreased the insulin signals including phosphorylated insulin receptor (p-IR), phosphorylated insulin receptor substrate 1 (p-IRS1), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3β (p-GSK3β) and phosphorylated extracellular regulated protein kinases (p-ERK1/2) in the brain, though insulin expression in both hippocampus and profrontal cortex was increased. In parallel, BPA exposure might contribute to glucose transport disturbance in the brain since the expression of glucose transporters were markedly decreased. In conclusion, BPA exposure perturbs the insulin signaling and glucose transport in the brain, therefore, it might be a risk factor for brain insulin resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

Microstructural White Matter Changes Underlying Cognitive and Behavioural Impairment in ALS – An In Vivo Study Using DTI

PubMed Central

Kasper, Elisabeth; Schuster, Christina; Machts, Judith; Kaufmann, Joern; Bittner, Daniel; Vielhaber, Stefan; Benecke, Reiner; Teipel, Stefan; Prudlo, Johannes

2014-01-01

Background A relevant fraction of patients with amyotrophic lateral sclerosis (ALS) exhibit a fronto-temporal pattern of cognitive and behavioural disturbances with pronounced deficits in executive functioning and cognitive control of behaviour. Structural imaging shows a decline in fronto-temporal brain areas, but most brain imaging studies did not evaluate cognitive status. We investigated microstructural white matter changes underlying cognitive impairment using diffusion tensor imaging (DTI) in a large cohort of ALS patients. Methods We assessed 72 non-demented ALS patients and 65 matched healthy control subjects using a comprehensive neuropsychological test battery and DTI. We compared DTI measures of fiber tract integrity using tract-based spatial statistics among ALS patients with and without cognitive impairment and healthy controls. Neuropsychological performance and behavioural measures were correlated with DTI measures. Results Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts, including the corticospinal tract and the body of corpus callosum. Those with impairments (ca. 30%) additionally presented significant white matter alterations in extra-motor regions, particularly the frontal lobe. Executive and memory performance and behavioural measures were correlated with fiber tract integrity in large association tracts. Conclusion In non-demented cognitively impaired ALS patients, white matter changes measured by DTI are related to disturbances of executive and memory functions, including prefrontal and temporal regions. In a group comparison, DTI is able to observe differences between cognitively unimpaired and impaired ALS patients. PMID:25501028

Imaging evidence for disturbances in multiple learning and memory systems in persons with autism spectrum disorders.

PubMed

Goh, Suzanne; Peterson, Bradley S

2012-03-01

The aim of this article is to review neuroimaging studies of autism spectrum disorders (ASD) that examine declarative, socio-emotional, and procedural learning and memory systems. We conducted a search of PubMed from 1996 to 2010 using the terms 'autism,''learning,''memory,' and 'neuroimaging.' We limited our review to studies correlating learning and memory function with neuroimaging features of the brain. The early literature supports the following preliminary hypotheses: (1) abnormalities of hippocampal subregions may contribute to autistic deficits in episodic and relational memory; (2) disturbances to an amygdala-based network (which may include the fusiform gyrus, superior temporal cortex, and mirror neuron system) may contribute to autistic deficits in socio-emotional learning and memory; and (3) abnormalities of the striatum may contribute to developmental dyspraxia in individuals with ASD. Characterizing the disturbances to learning and memory systems in ASD can inform our understanding of the neural bases of autistic behaviors and the phenotypic heterogeneity of ASD. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

The right cerebral hemisphere: emotion, music, visual-spatial skills, body-image, dreams, and awareness.

PubMed

Joseph, R

1988-09-01

Based on a review of numerous studies conducted on normal, neurosurgical and brain-injured individuals, the right cerebral hemisphere appears to be dominant in the perception and identification of environmental and nonverbal sounds; the analysis of geometric and visual space (e.g., depth perception, visual closure); somesthesis, stereognosis, the maintenance of the body image; the production of dreams during REM sleep; the perception of most aspects of musical stimuli; and the comprehension and expression of prosodic, melodic, visual, facial, and verbal emotion. When the right hemisphere is damaged a variety of cognitive abnormalities may result, including hemi-inattention and neglect, prosopagnosia, constructional apraxia, visual-perceptual disturbances, and agnosia for environmental, musical, and emotional sounds. Similarly, a myriad of affective abnormalities may occur, including indifference, depression, hysteria, gross social-emotional disinhibition, florid manic excitement, childishness, euphoria, impulsivity, and abnormal sexual behavior. Patients may become delusional, engage in the production of bizzare confabulations and experience a host of somatic disturbances such as pain and body-perceptual distortions. Based on studies of normal and "split-brain" functioning, it also appears that the right hemisphere maintains a highly developed social-emotional mental system and can independently perceive, recall and act on certain memories and experiences without the aid or active reflective participation of the left. This leads to situations in which the right and left halves of the brain sometime act in an uncooperative fashion, which gives rise to inter-manual and intra-psychic conflicts.

Contributions of the cerebellum to disturbed central processing of visceral stimuli in irritable bowel syndrome.

PubMed

Rosenberger, Christina; Thürling, Markus; Forsting, Michael; Elsenbruch, Sigrid; Timmann, Dagmar; Gizewski, Elke R

2013-04-01

There is evidence to support that the cerebellum contributes to the neural processing of both emotions and painful stimuli. This could be particularly relevant in conditions associated with chronic abdominal pain, such as the irritable bowel syndrome (IBS), which are often also characterized by affective disturbances. We aimed to test the hypothesis that in IBS, symptoms of anxiety and depression modulate brain activation during visceral stimulation within the cerebellum. We reanalyzed a previous data set from N = 15 female IBS patients and N = 12 healthy women with a specific focus on the cerebellum using advanced normalization methods. Rectal distension-induced brain activation was measured with functional magnetic resonance imaging using non-painful and painful rectal distensions. Symptoms of anxiety and depression, assessed with the Hospital Anxiety and Depression scale, were correlated with cerebellar activation within IBS patients. Within IBS, depression scores were associated with non-painful distension-induced activation in the right cerebellum primarily in Crus II and lobule VIIIb, and additionally in Crus I. Depression scores were also associated with painful distension-induced activation predominantly in vermal lobule V with some extension to the intermediate cerebellum. Anxiety scores correlated significantly with non-painful induced activation in Crus II. Symptoms of anxiety and depression, which are frequently found in chronic pain conditions like IBS, modulate activation during visceral sensory signals not only in cortical and subcortical brain areas but also in the cerebellum.

Disturbance of time orientation, attention, and verbal memory in amnesic patients with confabulation.

PubMed

Shingaki, Honoka; Park, Paeksoon; Ueda, Keita; Murai, Toshiya; Tsukiura, Takashi

2016-01-01

Confabulation is often observed in amnesic patients after brain damage. However, evidence regarding the relationship between confabulation and other neuropsychological functions is scarce. In addition, previous studies have proposed two possibilities of the relationship between confabulation and false memory, in which patients with confabulation are likely to retrieve false memories, or confabulations are relatively independent of false memories. The present study investigated how confabulation is related to various cognitive functions, including orientation, attention, frontal lobe function, memory, and mental status, and to false memories, as assessed by the Deese-Roediger-Mcdermott (DRM) paradigm. Patients with organic amnesia participated, and confabulations were evaluated using the Confabulation Battery. Amnestic patients were classified into two groups: confabulating (CP) and nonconfabulating patients (NCP). The CP group was significantly impaired in time orientation, attention, and verbal memory, compared to the NCP group and age-matched healthy controls (HC). Results of the DRM paradigm revealed no significant difference in false memory retrieval induced by critical lures across CP, NCP, and HC groups. Confabulating responses in organic amnesia could be in part induced by disturbance of time consciousness and attention control in severe impairment of verbal memories, and confabulation and false memory could be modulated by different cognitive systems.

Role of stress system disturbance and enhanced novelty response in spatial learning of NCAM-deficient mice.

PubMed

Brandewiede, Joerg; Jakovcevski, Mira; Stork, Oliver; Schachner, Melitta

2013-11-01

The neural cell adhesion molecule (NCAM) plays a crucial role in stress-related brain function, emotional behavior and memory formation. In this study, we investigated the functions of the glucocorticoid and serotonergic systems in mice constitutively deficient for NCAM (NCAM-/- mice). Our data provide evidence for a hyperfunction of the hypothalamic-pituitary-adrenal axis, with enlarged adrenal glands and increased stress-induced corticosterone release, but reduced hippocampal glucocorticoid receptor expression in NCAM-/- mice when compared to NCAM+/+ mice. We also obtained evidence for a hypofunction of 5-HT1A autoreceptors as indicated by increased 8-0H-DPAT-induced hypothermia. These findings suggest a disturbance of both humoral and neural stress systems in NCAM-/- mice. Accordingly, we not only confirmed previously observed hyperarousal of NCAM-/- mice in various anxiety tests, but also observed an increased response to novelty exposure in these animals. Spatial learning deficits of the NCAM-/- mice in a Morris Water maze persisted, even when mice were pretrained to prevent effects of novelty or stress. We suggest that NCAM-mediated processes are involved in both novelty/stress-related emotional behavior and in cognitive function during spatial learning.

Mitochondrial Aspects of Synaptic Dysfunction in Alzheimer’s Disease

PubMed Central

Cai, Qian; Tammineni, Prasad

2016-01-01

Alzheimer’s disease (AD) is characterized by brain deposition of amyloid plaques and tau neurofibrillary tangles along with steady cognitive decline. Synaptic damage, an early pathological event, correlates strongly with cognitive deficits and memory loss. Mitochondria are essential organelles for synaptic function. Neurons utilize specialized mechanisms to drive mitochondrial trafficking to synapses in which mitochondria buffer Ca2+ and serve as local energy sources by supplying ATP to sustain neurotransmitter release. Mitochondrial abnormalities are one of the earliest and prominent features in AD patient brains. Amyloid-β (Aβ) and tau both trigger mitochondrial alterations. Accumulating evidence suggests that mitochondrial perturbation acts as a key factor that is involved in synaptic failure and degeneration in AD. The importance of mitochondria in supporting synaptic function has made them a promising target of new therapeutic strategy for AD. Here, we review the molecular mechanisms regulating mitochondrial function at synapses, highlight recent findings on the disturbance of mitochondrial dynamics and transport in AD, and discuss how these alterations impact synaptic vesicle release and thus contribute to synaptic pathology associated with AD. PMID:27767992

Linking Resting-State Networks in the Prefrontal Cortex to Executive Function: A Functional Near Infrared Spectroscopy Study.

PubMed

Zhao, Jia; Liu, Jiangang; Jiang, Xin; Zhou, Guifei; Chen, Guowei; Ding, Xiao P; Fu, Genyue; Lee, Kang

2016-01-01

Executive function (EF) plays vital roles in our everyday adaptation to the ever-changing environment. However, limited existing studies have linked EF to the resting-state brain activity. The functional connectivity in the resting state between the sub-regions of the brain can reveal the intrinsic neural mechanisms involved in cognitive processing of EF without disturbance from external stimuli. The present study investigated the relations between the behavioral executive function (EF) scores and the resting-state functional network topological properties in the Prefrontal Cortex (PFC). We constructed complex brain functional networks in the PFC from 90 healthy young adults using functional near infrared spectroscopy (fNIRS). We calculated the correlations between the typical network topological properties (regional topological properties and global topological properties) and the scores of both the Total EF and components of EF measured by computer-based Cambridge Neuropsychological Test Automated Battery (CANTAB). We found that the Total EF scores were positively correlated with regional properties in the right dorsal superior frontal gyrus (SFG), whereas the opposite pattern was found in the right triangular inferior frontal gyrus (IFG). Different EF components were related to different regional properties in various PFC areas, such as planning in the right middle frontal gyrus (MFG), working memory mainly in the right MFG and triangular IFG, short-term memory in the left dorsal SFG, and task switch in the right MFG. In contrast, there were no significant findings for global topological properties. Our findings suggested that the PFC plays an important role in individuals' behavioral performance in the executive function tasks. Further, the resting-state functional network can reveal the intrinsic neural mechanisms involved in behavioral EF abilities.

Functional connectivity changes in adults with developmental stuttering: a preliminary study using quantitative electro-encephalography

PubMed Central

Joos, Kathleen; De Ridder, Dirk; Boey, Ronny A.; Vanneste, Sven

2014-01-01

Introduction: Stuttering is defined as speech characterized by verbal dysfluencies, but should not be seen as an isolated speech disorder, but as a generalized sensorimotor timing deficit due to impaired communication between speech related brain areas. Therefore we focused on resting state brain activity and functional connectivity. Method: We included 11 patients with developmental stuttering and 11 age matched controls. To objectify stuttering severity and the impact on quality of life (QoL), we used the Dutch validated Test for Stuttering Severity-Readers (TSS-R) and the Overall Assessment of the Speaker’s Experience of Stuttering (OASES), respectively. Furthermore, we used standardized low resolution brain electromagnetic tomography (sLORETA) analyses to look at resting state activity and functional connectivity differences and their correlations with the TSS-R and OASES. Results: No significant results could be obtained when looking at neural activity, however significant alterations in resting state functional connectivity could be demonstrated between persons who stutter (PWS) and fluently speaking controls, predominantly interhemispheric, i.e., a decreased functional connectivity for high frequency oscillations (beta and gamma) between motor speech areas (BA44 and 45) and the contralateral premotor (BA6) and motor (BA4) areas. Moreover, a positive correlation was found between functional connectivity at low frequency oscillations (theta and alpha) and stuttering severity, while a mixed increased and decreased functional connectivity at low and high frequency oscillations correlated with QoL. Discussion: PWS are characterized by decreased high frequency interhemispheric functional connectivity between motor speech, premotor and motor areas in the resting state, while higher functional connectivity in the low frequency bands indicates more severe speech disturbances, suggesting that increased interhemispheric and right sided functional connectivity is maladaptive. PMID:25352797

Increased Subjective Distaste and Altered Insula Activity to Umami Tastant in Patients with Bulimia Nervosa

PubMed Central

Setsu, Rikukage; Hirano, Yoshiyuki; Tokunaga, Miki; Takahashi, Toru; Numata, Noriko; Matsumoto, Koji; Masuda, Yoshitada; Matsuzawa, Daisuke; Iyo, Masaomi; Shimizu, Eiji; Nakazato, Michiko

2017-01-01

The aim of this study was to examine differences in brain neural activation in response to monosodium glutamate (MSG), the representative component of umami, between patients with bulimia nervosa (BN) and healthy women (HW) controls. We analyzed brain activity after ingestion of an MSG solution using functional magnetic resonance imaging (fMRI) in a group of women with BN (n = 18) and a group of HW participants (n = 18). Both groups also provided a subjective assessment of the MSG solution via a numerical rating scale. The BN group subjectively rated the MSG solution lower in pleasantness and liking than the control group, although no difference in subjective intensity was noted. The fMRI results demonstrated greater activation of the right insula in the BN group versus the control group. Compared with the HW controls, the BN patients demonstrated both altered taste perception-related brain activity and more negative hedonic scores in response to MSG stimuli. Different hedonic evaluation, expressed as the relative low pleasing taste of umami tastant and associated with altered insula function, may explain disturbed eating behaviors, including the imbalance in food choices, in BN patients. PMID:28993739

Increased Subjective Distaste and Altered Insula Activity to Umami Tastant in Patients with Bulimia Nervosa.

PubMed

Setsu, Rikukage; Hirano, Yoshiyuki; Tokunaga, Miki; Takahashi, Toru; Numata, Noriko; Matsumoto, Koji; Masuda, Yoshitada; Matsuzawa, Daisuke; Iyo, Masaomi; Shimizu, Eiji; Nakazato, Michiko

2017-01-01

The aim of this study was to examine differences in brain neural activation in response to monosodium glutamate (MSG), the representative component of umami, between patients with bulimia nervosa (BN) and healthy women (HW) controls. We analyzed brain activity after ingestion of an MSG solution using functional magnetic resonance imaging (fMRI) in a group of women with BN ( n  = 18) and a group of HW participants ( n  = 18). Both groups also provided a subjective assessment of the MSG solution via a numerical rating scale. The BN group subjectively rated the MSG solution lower in pleasantness and liking than the control group, although no difference in subjective intensity was noted. The fMRI results demonstrated greater activation of the right insula in the BN group versus the control group. Compared with the HW controls, the BN patients demonstrated both altered taste perception-related brain activity and more negative hedonic scores in response to MSG stimuli. Different hedonic evaluation, expressed as the relative low pleasing taste of umami tastant and associated with altered insula function, may explain disturbed eating behaviors, including the imbalance in food choices, in BN patients.

Loss of laterality in chronic cocaine users: an fMRI investigation of sensorimotor control.

PubMed

Hanlon, Colleen A; Wesley, Michael J; Roth, Alicia J; Miller, Mack D; Porrino, Linda J

2010-01-30

Movement disturbances are often overlooked consequences of chronic cocaine abuse. The purpose of this study was to systematically investigate sensorimotor performance in chronic cocaine users and characterize changes in brain activity among movement-related regions of interest (ROIs) in these users. Functional magnetic resonance imaging data were collected from 14 chronic cocaine users and 15 age- and gender-matched controls. All participants performed a sequential finger-tapping task with their dominant, right hand interleaved with blocks of rest. For each participant, percent signal change from rest was calculated for seven movement-related ROIs in both the left and right hemisphere. Cocaine users had significantly longer reaction times and higher error rates than controls. Whereas the controls used a left-sided network of motor-related brain areas to perform the task, cocaine users activated a less lateralized pattern of brain activity. Users had significantly more activity in the ipsilateral (right) motor and premotor cortical areas, anterior cingulate cortex and the putamen than controls. These data demonstrate that, in addition to the cognitive and affective consequences of chronic cocaine abuse, there are also pronounced alterations in sensorimotor control in these individuals, which are associated with functional alterations throughout movement-related neural networks.

Sex/gender differences in the brain and cognition in schizophrenia.

PubMed

Mendrek, Adrianna; Mancini-Marïe, Adham

2016-08-01

The early conceptualizations of schizophrenia have noted some sex/gender differences in epidemiology and clinical expression of the disorder. Over the past few decades, the interest in differences between male and female patients has expanded to encompass brain morphology and neurocognitive function. Despite some variability and methodological shortcomings, a few patterns emerge from the available literature. Most studies of gross neuroanatomy show more enlarged ventricles and smaller frontal lobes in men than in women with schizophrenia; finding reflecting normal sexual dimorphism. In comparison, studies of brain asymmetry and specific corticolimbic structures, suggest a disturbance in normal sexual dimorphism. The neurocognitive findings are somewhat consistent with this picture. Studies of cognitive functions mediated by the lateral frontal network tend to show sex differences in patients which are in the same direction as those observed in the general population, whereas studies of processes mediated by the corticolimbic system more frequently reveal reversal of normal sexual dimorphisms. These trends are faint and future research would need to delineate neurocognitive differences between men and women with various subtypes of schizophrenia (e.g., early versus late onset), while taking into consideration hormonal status and gender of tested participants. Copyright © 2015 Elsevier Ltd. All rights reserved.

White matter and cognition: making the connection

PubMed Central

Fields, R. Douglas

2016-01-01

Whereas the cerebral cortex has long been regarded by neuroscientists as the major locus of cognitive function, the white matter of the brain is increasingly recognized as equally critical for cognition. White matter comprises half of the brain, has expanded more than gray matter in evolution, and forms an indispensable component of distributed neural networks that subserve neurobehavioral operations. White matter tracts mediate the essential connectivity by which human behavior is organized, working in concert with gray matter to enable the extraordinary repertoire of human cognitive capacities. In this review, we present evidence from behavioral neurology that white matter lesions regularly disturb cognition, consider the role of white matter in the physiology of distributed neural networks, develop the hypothesis that white matter dysfunction is relevant to neurodegenerative disorders, including Alzheimer's disease and the newly described entity chronic traumatic encephalopathy, and discuss emerging concepts regarding the prevention and treatment of cognitive dysfunction associated with white matter disorders. Investigation of the role of white matter in cognition has yielded many valuable insights and promises to expand understanding of normal brain structure and function, improve the treatment of many neurobehavioral disorders, and disclose new opportunities for research on many challenging problems facing medicine and society. PMID:27512019

Cortical GABAergic neurons are more severely impaired by alkalosis than acidosis

PubMed Central

2013-01-01

Background Acid–base imbalance in various metabolic disturbances leads to human brain dysfunction. Compared with acidosis, the patients suffered from alkalosis demonstrate more severe neurological signs that are difficultly corrected. We hypothesize a causative process that the nerve cells in the brain are more vulnerable to alkalosis than acidosis. Methods The vulnerability of GABAergic neurons to alkalosis versus acidosis was compared by analyzing their functional changes in response to the extracellular high pH and low pH. The neuronal and synaptic functions were recorded by whole-cell recordings in the cortical slices. Results The elevation or attenuation of extracellular pH impaired these GABAergic neurons in terms of their capability to produce spikes, their responsiveness to excitatory synaptic inputs and their outputs via inhibitory synapses. Importantly, the dysfunction of these active properties appeared severer in alkalosis than acidosis. Conclusions The severer impairment of cortical GABAergic neurons in alkalosis patients leads to more critical neural excitotoxicity, so that alkalosis-induced brain dysfunction is difficultly corrected, compared to acidosis. The vulnerability of cortical GABAergic neurons to high pH is likely a basis of severe clinical outcomes in alkalosis versus acidosis. PMID:24314112

Ethylene glycol ethers induce apoptosis and disturb glucose metabolism in the rat brain.

PubMed

Pomierny, Bartosz; Krzyżanowska, Weronika; Niedzielska, Ewa; Broniowska, Żaneta; Budziszewska, Bogusława

2016-02-01

Ethylene glycol ethers (EGEs) are compounds widely used in industry and household products, but their potential, adverse effect on brain is poorly understood, so far. The aim of the present study was to determine whether 4-week administration of 2-buthoxyethanol (BE), 2-phenoxyethanol (PHE), and 2-ethoxyethanol (EE) induces apoptotic process in the rat hippocampus and frontal cortex, and whether their adverse effect on the brain cells can result from disturbances in the glucose metabolism. Experiments were conducted on 40 rats, exposed to BE, PHE, EE, saline or sunflower oil for 4 weeks. Markers of apoptosis and glucose metabolism were determined in frontal cortex and hippocampus by western blot, ELISA, and fluorescent-based assays. BE and PHE, but not EE, increased expression of the active form of caspase-3 in the examined brain regions. BE and PHE increased caspase-9 level in the cortex and PHE also in the hippocampus. BE and PHE increased the level of pro-apoptotic proteins (Bax, Bak) and/or reduced the concentration of anti-apoptotic proteins (Bcl-2, Bcl-xL); whereas, the effect of BE was observed mainly in the cortex and that of PHE in the hippocampus. It has also been found that PHE increased brain glucose level, and both BE and PHE elevated pyruvate and lactate concentration. It can be concluded that chronic treatment with BE and PHE induced mitochondrial pathway of apoptosis, and disturbed glucose metabolism in the rat brain. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Adenosine receptors as markers of brain iron deficiency: Implications for Restless Legs Syndrome.

PubMed

Quiroz, César; Gulyani, Seema; Ruiqian, Wan; Bonaventura, Jordi; Cutler, Roy; Pearson, Virginia; Allen, Richard P; Earley, Christopher J; Mattson, Mark P; Ferré, Sergi

2016-12-01

Deficits of sensorimotor integration with periodic limb movements during sleep (PLMS) and hyperarousal and sleep disturbances in Restless Legs Syndrome (RLS) constitute two pathophysiologically distinct but interrelated clinical phenomena, which seem to depend mostly on alterations in dopaminergic and glutamatergic neurotransmission, respectively. Brain iron deficiency is considered as a main pathogenetic mechanism in RLS. Rodents with brain iron deficiency represent a valuable pathophysiological model of RLS, although they do not display motor disturbances. Nevertheless, they develop the main neurochemical dopaminergic changes found in RLS, such as decrease in striatal dopamine D 2 receptor density. On the other hand, brain iron deficient mice exhibit the characteristic pattern of hyperarousal in RLS, providing a tool to find the link between brain iron deficiency and sleep disturbances in RLS. The present study provides evidence for a role of the endogenous sleep-promoting factor adenosine. Three different experimental preparations, long-term (22 weeks) severe or moderate iron-deficient (ID) diets (3- or 7-ppm iron diet) in mice and short-term (3 weeks) severe ID diet (3-ppm iron diet) in rats, demonstrated a significant downregulation (Western blotting in mouse and radioligand binding saturation experiments in rat brain tissue) of adenosine A 1 receptors (A1R) in the cortex and striatum, concomitant to striatal D2R downregulation. On the other hand, the previously reported upregulation of adenosine A 2A receptors (A2AR) was only observed with severe ID in both mice and rats. The results suggest a key role for A1R downregulation in the PLMS and hyperarousal in RLS. Published by Elsevier Ltd.

Design for an aging brain.

PubMed

Thaler, David S

2002-01-01

Vaillancourt and Newell (Neurobiol. of Aging 2001) show that although many aging systems decrease in complexity as anticipated by Lipsitz and Goldberger (JAMA 1992), other aging systems increase in complexity. Vaillancourt and Newell explain the discrepancy by proposing that systems with a point attractor decrease in complexity with age, whereas those with an oscillating attractor increase in complexity with age. Vaillancourt and Newell are certainly correct that no one direction fits all results. Aging and death sometimes follow from a system being too simple, or, too complex. A perspective, based on the work of W. Ross Ashby (1956 and http://pespmc1.vub.ac.be/ASHBBOOK.html) is used in this commentary to consider why some systems become apparently more simple and others more complex as they age. In this Ashby-inspired view the measured complexity of a system's Responses to Disturbances is proportional to the ratio D/R, where D and R are sets containing the variety of possible disturbances and responses. The model expands on Ashby's by proposing that D consists of two components, Dp and Du. Dp consists of disturbances that are a function of the system's perception. Responses to Dp are often anticipatory and the response itself dominates the outcome. Du are disturbances that are unavoidable. Outcomes decrease or increase in measured entropy as a function of changes in (Dp + Du)/R. The variety of elements in both Dp and R decrease with age. When D/R decreases with age, the system shows less complexity. Conversely when D/R increases with Age, the results become more entropic.

Sucrose preload reduces snacking after mild mental stress in healthy participants as a function of 5-hydroxytryptamine transporter gene promoter polymorphism.

PubMed

Markus, C Rob; Jonkman, Lisa M; Capello, Aimee; Leinders, Sacha; Hüsch, Fabian

2015-01-01

Brain serotonin (5-hydroxytryptamine, 5-HT) dysfunction is considered to promote food intake and eating-related disturbances, especially under stress or negative mood. Vulnerability for 5-HT disturbances is considered to be genetically determined, including a short (S) allele polymorphism in the serotonin transporter gene (5-HTTLPR) that is associated with lower serotonin function. Since 5-HT function may be slightly increased by carbohydrate consumption, S-allele 5-HTTLPR carriers in particular may benefit from a sugar-preload due to their enhanced 5-HT vulnerability. The aim of the current study was to investigate whether a sugar-containing preload may reduce appetite and energy intake after exposure to stress to induce negative mood, depending on genetic 5-HT vulnerability. From a population of 771 healthy young male and female genotyped college students 31 S/S carriers (8 males, 23 females) and 26 long allele (L/L) carriers (9 males, 17 females) (mean ± S.D. 22 ± 1.6 years; body mass index, BMI, 18-33 kg/m(2)) were monitored for changes in appetite and snacking behavior after stress exposure. Results revealed an increased energy intake after mild mental stress (negative mood) mainly for high-fat sweet foods, which was significantly greater in S/S carriers, and only in these genotypes this intake was significantly reduced by a sucrose-containing preload. Although alternative explanations are possible, it is suggested that S/S participants may have enhanced brain (hypothalamic) 5-HT responsiveness to food that makes them more susceptible to the beneficial satiation effects of a sucrose-preload as well as to the negative effects of mild mental stress on weight gain.

Mentalization and the left inferior frontal gyrus and insula.

PubMed

McAdams, Carrie J; Harper, Jessica A; Van Enkevort, Erin

2018-05-01

To determine if an interpersonal attribution bias associated with self-perception, the externalizing bias, was related to neural activations during mentalization. A functional magnetic resonance imaging task involving verbal appraisals measured neural activations when thinking about oneself and others in 59 adults, including healthy women as well as women with and recovered from anorexia nervosa. Whole-brain regressions correlated brain function during mentalization with the externalizing bias measured using the Internal, Personal, and Situational Attributions Questionnaire. Women with anorexia nervosa had a lower externalizing bias, demonstrating a tendency to self-attribute more negative than positive social interactions, unlike the other groups. The externalizing bias was correlated with activation of the left inferior frontal gyrus and posterior insula, when comparing thinking about others evaluating oneself with direct self-evaluation. Externalizing biases may provide an office-based assay reflecting neurocognitive disturbances in social self-perception that are common during anorexia nervosa. Copyright © 2018 John Wiley & Sons, Ltd and Eating Disorders Association.

[Mobile phones radiate--risk to the health?].

PubMed

Jokela, Kari; Auvinen, Anssi; Hämäläinen, Heikki

2011-01-01

The mobile phones radiate electromagnetic energy which is partly absorbed into the tissues in the vicinity of the phone. The minor heating, in maximum up to 0.3 degrees C, may cause some alterations in the expression of genes and proteins similar to physiological response to other stimuli. Biophysical studies at the cellular and molecular level have not revealed any well established interaction mechanism, through which mobile phone radiation could induce toxic effects below the thermal effect level. Research results on various biological effects in vitro and in vivo are continuously published but there is no consistent evidence on well established harmful effects. The mobile phone radiation is not carcinogenic for experimental animals or genotoxic for cells. According to epidemiological studies and psychophysiological brain function studies the use of mobile phones does not seem to increase the risk of tumors in the head and brain or disturb the function of central nervous system. However, there is a need for more research on the long-term effects of mobile phone radiation particularly on children.

Report and Research Agenda of the American Geriatrics Society and National Institute on Aging Bedside-to-Bench Conference on Sleep, Circadian Rhythms, and Aging: New Avenues for Improving Brain Health, Physical Health, and Functioning

PubMed Central

Fung, Constance H.; Vitiello, Michael V.; Alessi, Cathy A.; Kuchel, George A.

2016-01-01

The American Geriatrics Society, with support from the National Institute on Aging and other funders, held its eighth Bedside-to-Bench research conference, entitled “Sleep, Circadian Rhythms, and Aging: New Avenues for Improving Brain Health, Physical Health and Functioning,” October 4 to 6, 2015, in Bethesda, Maryland. Part of a conference series addressing three common geriatric syndromes—delirium, sleep and circadian rhythm (SCR) disturbance, and voiding dysfunction—the series highlighted relationships and pertinent clinical and pathophysiological commonalities between these three geriatric syndromes. The conference provided a forum for discussing current sleep, circadian rhythm, and aging research; identifying gaps in knowledge; and developing a research agenda to inform future investigative efforts. The conference also promoted networking among developing researchers, leaders in the field of SCR and aging, and National Institutes of Health program personnel. PMID:27858974

Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety.

PubMed

Dolcos, Sanda; Hu, Yifan; Iordan, Alexandru D; Moore, Matthew; Dolcos, Florin

2016-02-01

Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain-personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Circadian misalignment, reward-related brain function, and adolescent alcohol involvement.

PubMed

Hasler, Brant P; Clark, Duncan B

2013-04-01

Developmental changes in sleep and circadian rhythms that occur during adolescence may contribute to reward-related brain dysfunction, and consequently increase the risk of alcohol use disorders (AUDs). This review (i) describes marked changes in circadian rhythms, reward-related behavior and brain function, and alcohol involvement that occur during adolescence, (ii) offers evidence that these parallel developmental changes are associated, and (iii) posits a conceptual model by which misalignment between sleep-wake timing and endogenous circadian timing may increase the risk of adolescent AUDs by altering reward-related brain function. The timing of sleep shifts later throughout adolescence, in part due to developmental changes in endogenous circadian rhythms, which tend to become more delayed. This tendency for delayed sleep and circadian rhythms is at odds with early school start times during secondary education, leading to misalignment between many adolescents' sleep-wake schedules and their internal circadian timing. Circadian misalignment is associated with increased alcohol use and other risk-taking behaviors, as well as sleep loss and sleep disturbance. Growing evidence indicates that circadian rhythms modulate the reward system, suggesting that circadian misalignment may impact adolescent alcohol involvement by altering reward-related brain function. Neurocognitive function is also subject to sleep and circadian influence, and thus circadian misalignment may also impair inhibitory control and other cognitive processes relevant to alcohol use. Specifically, circadian misalignment may further exacerbate the cortical-subcortical imbalance within the reward circuit, an imbalance thought to explain increased risk-taking and sensation-seeking during adolescence. Adolescent alcohol use is highly contextualized, however, and thus studies testing this model will also need to consider factors that may influence both circadian misalignment and alcohol use. This review highlights growing evidence supporting a path by which circadian misalignment may disrupt reward mechanisms, which may in turn accelerate the transition from alcohol use to AUDs in vulnerable adolescents. Copyright © 2013 by the Research Society on Alcoholism.

Pathophysiology of increased cerebrospinal fluid pressure associated to brain arteriovenous malformations: The hydraulic hypothesis.

PubMed

Rossitti, Sandro

2013-01-01

Brain arteriovenous malformations (AVMs) produce circulatory and functional disturbances in adjacent as well as in remote areas of the brain, but their physiological effect on the cerebrospinal fluid (CSF) pressure is not well known. The hypothesis of an intrinsic disease mechanism leading to increased CSF pressure in all patients with brain AVM is outlined, based on a theory of hemodynamic control of intracranial pressure that asserts that CSF pressure is a fraction of the systemic arterial pressure as predicted by a two-resistor series circuit hydraulic model. The resistors are the arteriolar resistance (that is regulated by vasomotor tonus), and the venous resistance (which is mechanically passive as a Starling resistor). This theory is discussed and compared with the knowledge accumulated by now on intravasal pressures and CSF pressure measured in patients with brain AVM. The theory provides a basis for understanding the occurrence of pseudotumor cerebri syndrome in patients with nonhemorrhagic brain AVMs, for the occurrence of local mass effect and brain edema bordering unruptured AVMs, and for the development of hydrocephalus in patients with unruptured AVMs. The theory also contributes to a better appreciation of the pathophysiology of dural arteriovenous fistulas, of vein of Galen aneurismal malformation, and of autoregulation-related disorders in AVM patients. The hydraulic hypothesis provides a comprehensive frame to understand brain AVM hemodynamics and its effect on the CSF dynamics.

Pathophysiology of increased cerebrospinal fluid pressure associated to brain arteriovenous malformations: The hydraulic hypothesis

PubMed Central

Rossitti, Sandro

2013-01-01

Background: Brain arteriovenous malformations (AVMs) produce circulatory and functional disturbances in adjacent as well as in remote areas of the brain, but their physiological effect on the cerebrospinal fluid (CSF) pressure is not well known. Methods: The hypothesis of an intrinsic disease mechanism leading to increased CSF pressure in all patients with brain AVM is outlined, based on a theory of hemodynamic control of intracranial pressure that asserts that CSF pressure is a fraction of the systemic arterial pressure as predicted by a two-resistor series circuit hydraulic model. The resistors are the arteriolar resistance (that is regulated by vasomotor tonus), and the venous resistance (which is mechanically passive as a Starling resistor). This theory is discussed and compared with the knowledge accumulated by now on intravasal pressures and CSF pressure measured in patients with brain AVM. Results: The theory provides a basis for understanding the occurrence of pseudotumor cerebri syndrome in patients with nonhemorrhagic brain AVMs, for the occurrence of local mass effect and brain edema bordering unruptured AVMs, and for the development of hydrocephalus in patients with unruptured AVMs. The theory also contributes to a better appreciation of the pathophysiology of dural arteriovenous fistulas, of vein of Galen aneurismal malformation, and of autoregulation-related disorders in AVM patients. Conclusions: The hydraulic hypothesis provides a comprehensive frame to understand brain AVM hemodynamics and its effect on the CSF dynamics. PMID:23607064

Functional network connectivity underlying food processing: disturbed salience and visual processing in overweight and obese adults.

PubMed

Kullmann, Stephanie; Pape, Anna-Antonia; Heni, Martin; Ketterer, Caroline; Schick, Fritz; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert; Veit, Ralf

2013-05-01

In order to adequately explore the neurobiological basis of eating behavior of humans and their changes with body weight, interactions between brain areas or networks need to be investigated. In the current functional magnetic resonance imaging study, we examined the modulating effects of stimulus category (food vs. nonfood), caloric content of food, and body weight on the time course and functional connectivity of 5 brain networks by means of independent component analysis in healthy lean and overweight/obese adults. These functional networks included motor sensory, default-mode, extrastriate visual, temporal visual association, and salience networks. We found an extensive modulation elicited by food stimuli in the 2 visual and salience networks, with a dissociable pattern in the time course and functional connectivity between lean and overweight/obese subjects. Specifically, only in lean subjects, the temporal visual association network was modulated by the stimulus category and the salience network by caloric content, whereas overweight and obese subjects showed a generalized augmented response in the salience network. Furthermore, overweight/obese subjects showed changes in functional connectivity in networks important for object recognition, motivational salience, and executive control. These alterations could potentially lead to top-down deficiencies driving the overconsumption of food in the obese population.

Repetitive transcranial magnetic stimulation improves consciousness disturbance in stroke patients: A quantitative electroencephalography spectral power analysis.

PubMed

Xie, Ying; Zhang, Tong

2012-11-05

Repetitive transcranial magnetic stimulation is a noninvasive treatment technique that can directly alter cortical excitability and improve cerebral functional activity in unconscious patients. To investigate the effects and the electrophysiological changes of repetitive transcranial magnetic stimulation cortical treatment, 10 stroke patients with non-severe brainstem lesions and with disturbance of consciousness were treated with repetitive transcranial magnetic stimulation. A quantitative electroencephalography spectral power analysis was also performed. The absolute power in the alpha band was increased immediately after the first repetitive transcranial magnetic stimulation treatment, and the energy was reduced in the delta band. The alpha band relative power values slightly decreased at 1 day post-treatment, then increased and reached a stable level at 2 weeks post-treatment. Glasgow Coma Score and JFK Coma Recovery Scale-Revised score were improved. Relative power value in the alpha band was positively related to Glasgow Coma Score and JFK Coma Recovery Scale-Revised score. These data suggest that repetitive transcranial magnetic stimulation is a noninvasive, safe, and effective treatment technology for improving brain functional activity and promoting awakening in unconscious stroke patients.

Brain natriuretic peptide and right heart dysfunction after heart transplantation.

PubMed

Talha, Samy; Charloux, Anne; Piquard, François; Geny, Bernard

2017-06-01

Heart transplantation (HT) should normalize cardiac endocrine function, but brain natriuretic peptide (BNP) levels remain elevated after HT, even in the absence of left ventricular hemodynamic disturbance or allograft rejection. Right ventricle (RV) abnormalities are common in HT recipients (HTx), as a result of engraftment process, tricuspid insufficiency, and/or repeated inflammation due to iterative endomyocardial biopsies. RV function follow-up is vital for patient management as RV dysfunction is a recognized cause of in-hospital death and is responsible for a worse prognosis. Interestingly, few and controversial data are available concerning the relationship between plasma BNP levels and RV functional impairment in HTx. This suggests that infra-clinical modifications, such as subtle immune system disorders or hypoxic conditions, might influence BNP expression. Nevertheless, due to other altered circulating molecular forms of BNP, a lack of specificity of BNP assays is described in heart failure patients. This phenomenon could exist in HT population and could explain elevated BNP plasmatic levels despite a normal RV function. In clinical practice, intra-individual change in BNP over time, rather than absolute BNP values, might be more helpful in detecting right cardiac dysfunction in HTx. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Visuospatial Attention Disturbance in Duchenne Muscular Dystrophy

ERIC Educational Resources Information Center

De Moura, Maria Clara Drummond Soares; do Valle, Luiz Eduardo Ribeiro; Resende, Maria Bernadete Dutra; Pinto, Katia Osternack

2010-01-01

Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

Too big or too narrow? Disturbance characteristics determine the functional resilience in virtual microbial ecosystems

NASA Astrophysics Data System (ADS)

König, Sara; Firle, Anouk-Letizia; Koehnke, Merlin; Banitz, Thomas; Frank, Karin

2017-04-01

In general ecology, there is an ongoing debate about the influence of fragmentation on extinction thresholds. Whether this influence is positive or negative depends on the considered type of fragmentation: whereas habitat fragmentation often has a negative influence on population extinction thresholds, spatially fragmented disturbances are observed to have mostly positive effects on the extinction probability. Besides preventing population extinction, in soil systems ecology we are interested in analyzing how ecosystem functions are maintained despite disturbance events. Here, we analyzed the influence of disturbance size and fragmentation on the functional resilience of a microbial soil ecosystem. As soil is a highly heterogeneous environment exposed to disturbances of different spatial configurations, the identification of critical disturbance characteristics for maintaining its functions is crucial. We used the numerical simulation model eColony considering bacterial growth, degradation and dispersal for analyzing the dynamic response of biodegradation examplary for an important microbial ecosystem service to disturbance events of different spatial configurations. We systematically varied the size and the degree of fragmentation of the affected area (disturbance pattern). We found that the influence of the disturbance size on functional recovery and biodegradation performance highly depends on the spatial fragmentation of the disturbance. Generally, biodegradation performance decreases with increasing clumpedness and increasing size of the affected area. After spatially correlated disturbance events, biodegradation performance decreases linear with increasing disturbance size. After spatially fragmented disturbance events, on the other hand, an increase in disturbance size has no influence on the biodegradation performance until a critical disturbance size is reached. Is the affected area bigger than this critical size, the functional performance decreases dramatically. Under recurrent disturbance events, this threshold is shifted to lower disturbance sizes. The more frequent disturbances are recurring, the lower is the critical disturbance size. Our simulation results indicate the importance of spatial characteristics of disturbance events for the functional resilience of microbial ecosystems. Critical values for disturbance size and fragmentation emerge from an interplay between both characteristics. In consequence, a precise definition of the specific disturbance regime is necessary for analysing functional resilience. With this study, we show that we need to consider the influence of fragmentation in terrestrial environments not only on population extincions but also on the resilience of ecosystem functions. Moreover, spatial disturbance characteristics - which are widely discussed on landscape scale - are an important factor on smaller scales, too.

Post-stroke balance rehabilitation under multi-level electrotherapy: a conceptual review

PubMed Central

Dutta, Anirban; Lahiri, Uttama; Das, Abhijit; Nitsche, Michael A.; Guiraud, David

2014-01-01

Stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow thereby preventing delivery of oxygen and nutrients. About half of the stroke survivors are left with some degree of disability. Innovative methodologies for restorative neurorehabilitation are urgently required to reduce long-term disability. The ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function, and connections is called neuroplasticity. Neuroplasticity is involved in post-stroke functional disturbances, but also in rehabilitation. It has been shown that active cortical participation in a closed-loop brain machine interface (BMI) can induce neuroplasticity in cortical networks where the brain acts as a controller, e.g., during a visuomotor task. Here, the motor task can be assisted with neuromuscular electrical stimulation (NMES) where the BMI will act as a real-time decoder. However, the cortical control and induction of neuroplasticity in a closed-loop BMI is also dependent on the state of brain, e.g., visuospatial attention during visuomotor task performance. In fact, spatial neglect is a hidden disability that is a common complication of stroke and is associated with prolonged hospital stays, accidents, falls, safety problems, and chronic functional disability. This hypothesis and theory article presents a multi-level electrotherapy paradigm toward motor rehabilitation in virtual reality that postulates that while the brain acts as a controller in a closed-loop BMI to drive NMES, the state of brain can be can be altered toward improvement of visuomotor task performance with non-invasive brain stimulation (NIBS). This leads to a multi-level electrotherapy paradigm where a virtual reality-based adaptive response technology is proposed for post-stroke balance rehabilitation. In this article, we present a conceptual review of the related experimental findings. PMID:25565937

Hypoxia-ischemia brain damage disrupts brain cholesterol homeostasis in neonatal rats.

PubMed

Yu, Z; Li, S; Lv, S H; Piao, H; Zhang, Y H; Zhang, Y M; Ma, H; Zhang, J; Sun, C K; Li, A P

2009-08-01

The first 3 weeks of life is the peak time of oligodendrocytes development and also the critical period of cholesterol increasing dramatically in central nervous system in rats. Neonatal hypoxia-ischemia (HI) brain damage happening in this period may disturb the brain cholesterol balance as well as white matter development. To test this hypothesis, postnatal day 7 (P7) Sprague-Dawley rats were subjected to HI insult. Cholesterol concentrations from brain and plasma were measured. White matter integrity was evaluated by densitometric analysis of myelin basic protein (MBP) immunostaining and electron microscopy. Brain TNF-alpha and IL-6 levels were also measured. HI-induced brain cholesterol, but not the plasma cholesterol, levels decreased significantly during the first three days after HI compared with naïve and sham operated rats (p<0.05). Obvious hypomyelination was indicated by marked reductions in MBP immunostaining on both P10 and P14 (p<0.01) and less and thinner myelinated axons were detected on P21 by electron microscopy observation. High expressions of brain TNF-alpha and IL-6 12 h after HI (p<0.05) were also observed. The present work provides evidence that HI insult destroyed brain cholesterol homeostasis, which might be important in the molecular pathology of hypoxic-ischemic white matter injury. Proinflammatory cytokines insulting oligodendrocytes, may cause cholesterol unbalance. Furthermore, specific therapeutic interventions to maintain brain cholesterol balance may be effective for the recovery of white matter function. Georg Thieme Verlag KG Stuttgart New York.

Ammonia-induced mitochondrial dysfunction and energy metabolism disturbances in isolated brain and liver mitochondria, and the effect of taurine administration: relevance to hepatic encephalopathy treatment

PubMed Central

Niknahad, Hossein; Jamshidzadeh, Akram; Zarei, Mahdi; Ommati, Mohammad Mehdi

2017-01-01

Introduction Ammonia-induced oxidative stress, mitochondrial dysfunction, and energy crisis are known as some the major mechanisms of brain injury in hepatic encephalopathy (HE). Hyperammonemia also affects the liver and hepatocytes. Therefore, targeting mitochondria seems to be a therapeutic point of intervention in the treatment of HE. Taurine is an abundant amino acid in the human body. Several biological functions including the mitochondrial protective properties are attributed to this amino acid. The aim of this study is to evaluate the effect of taurine administration on ammonia-induced mitochondrial dysfunction. Material and methods Isolated mice liver and brain mitochondria were exposed to different concentrations of ammonia (1, 5, 10, and 20 mM) and taurine (1, 5, and 10 mM), and several mitochondrial indices were assessed. Results It was found that ammonia inhibited mitochondrial dehydrogenases activity caused collapse of mitochondrial membrane potential (MMP), induced mitochondrial swelling (MPP), and increased reactive oxygen species (ROS) in isolated liver and brain mitochondria. Furthermore, a significant amount of lipid peroxidation (LPO), along with glutathione (GSH) and ATP depletion, was detected in ammonia exposed mitochondria. Taurine administration (5 and 10 mM) mitigated ammonia-induced mitochondrial dysfunction. Conclusions The current investigation demonstrates that taurine is instrumental in preserving brain and liver mitochondrial function in a hyperammonemic environment. The data suggest taurine as a potential protective agent with a therapeutic capability against hepatic encephalopathy and hyperammonemia. PMID:29062904

Involvement of the endocannabinoid system in reward processing in the human brain.

PubMed

van Hell, Hendrika H; Jager, Gerry; Bossong, Matthijs G; Brouwer, Annelies; Jansma, J Martijn; Zuurman, Lineke; van Gerven, Joop; Kahn, René S; Ramsey, Nick F

2012-02-01

Disturbed reward processing in humans has been associated with a number of disorders, such as depression, addiction, and attention-deficit hyperactivity disorder. The endocannabinoid (eCB) system has been implicated in reward processing in animals, but in humans, the relation between eCB functioning and reward is less clear. The current study uses functional magnetic resonance imaging (fMRI) to investigate the role of the eCB system in reward processing in humans by examining the effect of the eCB agonist Δ(9)-tetrahydrocannabinol (THC) on reward-related brain activity. Eleven healthy males participated in a randomized placebo-controlled pharmacological fMRI study with administration of THC to challenge the eCB system. We compared anticipatory and feedback-related brain activity after placebo and THC, using a monetary incentive delay task. In this task, subjects are notified before each trial whether a correct response is rewarded ("reward trial") or not ("neutral trial"). Subjects showed faster reaction times during reward trials compared to neutral trials, and this effect was not altered by THC. THC induced a widespread attenuation of the brain response to feedback in reward trials but not in neutral trials. Anticipatory brain activity was not affected. These results suggest a role for the eCB system in the appreciation of rewards. The involvement of the eCB system in feedback processing may be relevant for disorders in which appreciation of natural rewards may be affected such as addiction.

Manipulation of colony environment modulates honey bee aggression and brain gene expression.

PubMed

Rittschof, C C; Robinson, G E

2013-11-01

The social environment plays an essential role in shaping behavior for most animals. Social effects on behavior are often linked to changes in brain gene expression. In the honey bee (Apis mellifera L.), social modulation of individual aggression allows colonies to adjust the intensity with which they defend their hive in response to predation threat. Previous research has showed social effects on both aggression and aggression-related brain gene expression in honey bees, caused by alarm pheromone and unknown factors related to colony genotype. For example, some bees from less aggressive genetic stock reared in colonies with genetic predispositions toward increased aggression show both increased aggression and more aggressive-like brain gene expression profiles. We tested the hypothesis that exposure to a colony environment influenced by high levels of predation threat results in increased aggression and aggressive-like gene expression patterns in individual bees. We assessed gene expression using four marker genes. Experimentally induced predation threats modified behavior, but the effect was opposite of our predictions: disturbed colonies showed decreased aggression. Disturbed colonies also decreased foraging activity, suggesting that they did not habituate to threats; other explanations for this finding are discussed. Bees in disturbed colonies also showed changes in brain gene expression, some of which paralleled behavioral findings. These results show that bee aggression and associated molecular processes are subject to complex social influences. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

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.

Certain features of the cochleovestibular syndrome in the residual stage of traumatic brain disease

NASA Technical Reports Server (NTRS)

Garshin, M. I.; Volyanskiy, V. Y.

1980-01-01

Caloric and rotation tests were applied to the study of the vestibular analyser in 84 patients in the residual state of traumatic disease of the brain. Vestibular disturbances of different degree revealed in 79 patients were as a rule accomplished by cochlear derangement. In the majority of patients the vestibular syndrome was supratentorial with the involvement of the diencephal-hypothalmic, subcortical, and cortical levels of the brain. Vestibular dysfunction correlated with such factors as severity of the sustained craniocerebral traum, duration of the posttraumatic period, and, particularly, with the character of the residual neurological syndrome. In accordance with the latter, it is recommended that vestibular disturbances be treated in the residual period of closed craniocerebral injuries with due regard for the principal pathophysiological mechanisms of the underlying neurological syndrome.

Dimensions of personality disturbance after focal brain damage: investigation with the Iowa Scales of Personality Change.

PubMed

Barrash, Joseph; Asp, Erik; Markon, Kristian; Manzel, Kenneth; Anderson, Steven W; Tranel, Daniel

2011-10-01

This study employed a multistep, rational-empirical approach to identify dimensions of personality disturbance in brain-damaged individuals: (a) Five dimensions were hypothesized based on empirical literature and conceptual grounds; (b) principal components analysis was performed on the Iowa Scales of Personality Change (ISPC) to determine the pattern of covariance among 30 personality characteristics; (c) when discrepancies existed between principal components analysis results and conceptually based dimensions, empirical findings and clinical considerations were weighed to determine assignment of ISPC scales to dimensions; (d) the fit of data to the refined dimensions was assessed by examination of intercorrelations; (e) differential predictions concerning the relationship of dimensions to ventromedial prefrontal cortex (vmPFC) damage were tested. This process resulted in the specification of five dimensions: Disturbed Social Behavior, Executive/Decision-Making Deficits, Diminished Motivation/Hypo-Emotionality, Irascibility, and Distress. In accord with predictions, the 28 participants with vmPFC lesions, compared to 96 participants with focal lesions elsewhere in the brain, had significantly more Disturbed Social Behavior and Executive/Decision-Making Deficits and tended to have more Diminished Motivation/Hypo-Emotionality. Irascibility was not significantly higher among the vmPFC group, and the groups had very similar levels of Distress. The findings indicate that conceptually distinctive dimensions with differential relationships to vmPFC can be derived from the Iowa Scales of Personality Change.

PET imaging in the assessment of normal and impaired cognitive function.

PubMed

Silverman, Daniel H S; Alavi, Abass

2005-01-01

PET has been used to directly quantify several processes relevant to the status of cerebral health and function, including cerebral blood flow, cerebral blood volume, cerebral rate of oxygen metabolism, and cerebral glucose use. Clinically, the most commonly performed PET studies of the brain are performed with fluorine-18-fluorodeoxyglucose as the imaged radiopharmaceutical. Such scans have demonstrated diagnostic and prognostic use in evaluating patients who have cognitive impairment, and in distinguishing among primary neurodegenerative dementias and other causes of cognitive decline. In certain pathologic circumstances, the normal coupling between blood flow and metabolic needs may be disturbed, and changes in oxygen extraction fraction can have significant prognostic value.

Osmoregulation Requires Brain Expression of the Renal Na-K-2Cl Cotransporter NKCC2

PubMed Central

Konopacka, Agnieszka; Qiu, Jing; Yao, Song T.; Greenwood, Michael P.; Greenwood, Mingkwan; Lancaster, Thomas; Inoue, Wataru; de Souza Mecawi, Andre; Vechiato, Fernanda M.V.; de Lima, Juliana B.M.; Coletti, Ricardo; Hoe, See Ziau; Martin, Andrew; Lee, Justina; Joseph, Marina; Hindmarch, Charles; Paton, Julian; Antunes-Rodrigues, Jose; Bains, Jaideep

2015-01-01

The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution—rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats. PMID:25834041

Decreased GRK3 but not GRK2 expression in frontal cortex from bipolar disorder patients

PubMed Central

Rao, Jagadeesh S; Rapoport, Stanley I; Kim, Hyung-Wook

2009-01-01

Overactivation of G-protein mediated functions and altered G-protein regulation have been reported in bipolar disorder (BD) brain. Further, drugs effective in treating BD are reported to upregulate expression of G-protein receptor kinase (GRK) 3 in rat frontal cortex. We therefore hypothesized that some G-protein subunits and GRK levels would be reduced in the brains of BD patients. We determined protein and mRNA levels of G-protein β and γ subunits, GRK2, and GRK3 in postmortem frontal cortex from 10 BD patients and 10 age-matched controls by using immunoblots and real-time RT-PCR. There were the statistically significant decreases in protein and mRNA levels of G-protein subunits β and γ and of GRK3 in the BD brains but not a significant difference in the GRK2 level. Decreased expression of G-protein subunits and of GRK3 may alter neurotransmission, leading to disturbed cognition and behavior in BD. PMID:19400979

Optimism and the brain: trait optimism mediates the protective role of the orbitofrontal cortex gray matter volume against anxiety

PubMed Central

Hu, Yifan; Iordan, Alexandru D.; Moore, Matthew; Dolcos, Florin

2016-01-01

Converging evidence identifies trait optimism and the orbitofrontal cortex (OFC) as personality and brain factors influencing anxiety, but the nature of their relationships remains unclear. Here, the mechanisms underlying the protective role of trait optimism and of increased OFC volume against symptoms of anxiety were investigated in 61 healthy subjects, who completed measures of trait optimism and anxiety, and underwent structural scanning using magnetic resonance imaging. First, the OFC gray matter volume (GMV) was associated with increased optimism, which in turn was associated with reduced anxiety. Second, trait optimism mediated the relation between the left OFC volume and anxiety, thus demonstrating that increased GMV in this brain region protects against symptoms of anxiety through increased optimism. These results provide novel evidence about the brain–personality mechanisms protecting against anxiety symptoms in healthy functioning, and identify potential targets for preventive and therapeutic interventions aimed at reducing susceptibility and increasing resilience against emotional disturbances. PMID:26371336

Protective role of taurine in developing offspring affected by maternal alcohol consumption

PubMed Central

Ananchaipatana-Auitragoon, Pilant; Ananchaipatana-Auitragoon, Yutthana; Siripornpanich, Vorasith; Kotchabhakdi, Naiphinich

2015-01-01

Maternal alcohol consumption is known to affect offspring growth and development, including growth deficits, physical anomalies, impaired brain functions and behavioral disturbances. Taurine, a sulfur-containing amino acid, is essential during development, and continually found to be protective against neurotoxicity and various tissue damages including those from alcohol exposure. However, it is still unknown whether taurine can exert its protection during development of central nervous system and whether it can reverse alcohol damages on developed brain later in life. This study aims to investigate protective roles of taurine against maternal alcohol consumption on growth and development of offspring. The experimental protocol was conducted using ICR-outbred pregnant mice given 10 % alcohol, with or without maternal taurine supplementation during gestation and lactation. Pregnancy outcomes, offspring mortality and successive bodyweight until adult were monitored. Adult offspring is supplemented taurine to verify its ability to reverse damages on learning and memory through a water maze task performance. Our results demonstrate that offspring of maternal alcohol exposure, together with maternal taurine supplementation show conserved learning and memory, while that of offspring treated taurine later in life are disturbed. Taurine provides neuroprotective effects and preserves learning and memory processes when given together with maternal alcohol consumption, but not shown such effects when given exclusively in offspring. PMID:26648819

Predictors of cognitive and physical fatigue in post-acute mild-moderate traumatic brain injury.

PubMed

Schiehser, Dawn M; Delano-Wood, Lisa; Jak, Amy J; Hanson, Karen L; Sorg, Scott F; Orff, Henry; Clark, Alexandra L

2017-10-01

Post-traumatic fatigue (PTF) is a common, disabling, and often chronic symptom following traumatic brain injury (TBI). Yet, the impact of chronic cognitive and physical fatigue and their associations with psychiatric, sleep, cognitive, and psychosocial sequelae in mild-moderate TBI remain poorly understood. Sixty Veterans with a history of mild-moderate TBI and 40 Veteran controls (VC) were administered the Modified Fatigue Impact Scale, a validated measure of TBI-related cognitive and physical fatigue as well as measures of neuropsychiatric, psychosocial, sleep, and objective cognitive functioning. Compared to VC, TBI Veterans endorsed significantly greater levels of cognitive and physical fatigue. In TBI, psychiatric symptoms, sleep disturbance, and post-traumatic amnesia (PTA) were associated with both cognitive and physical fatigue, while loss of consciousness (LOC) and poor attention/processing speed were related to elevations in cognitive fatigue only. In regression analyses, anxiety, sleep disturbance, and LOC significantly predicted cognitive fatigue, while only post-traumatic stress symptoms and PTA contributed to physical fatigue. Cognitive and physical fatigue are problematic symptoms following mild-moderate TBI that are differentially associated with specific injury and psychiatric sequelae. Findings provide potential symptom targets for interventions aimed at ameliorating fatigue, and further underscore the importance of assessing and treating fatigue as a multi-dimensional symptom following TBI.

Connexin channels provide a target to manipulate brain endothelial calcium dynamics and blood–brain barrier permeability

PubMed Central

De Bock, Marijke; Culot, Maxime; Wang, Nan; Bol, Mélissa; Decrock, Elke; De Vuyst, Elke; da Costa, Anaelle; Dauwe, Ine; Vinken, Mathieu; Simon, Alexander M; Rogiers, Vera; De Ley, Gaspard; Evans, William Howard; Bultynck, Geert; Dupont, Geneviève; Cecchelli, Romeo; Leybaert, Luc

2011-01-01

The cytoplasmic Ca2+ concentration ([Ca2+]i) is an important factor determining the functional state of blood–brain barrier (BBB) endothelial cells but little is known on the effect of dynamic [Ca2+]i changes on BBB function. We applied different agonists that trigger [Ca2+]i oscillations and determined the involvement of connexin channels and subsequent effects on endothelial permeability in immortalized and primary brain endothelial cells. The inflammatory peptide bradykinin (BK) triggered [Ca2+]i oscillations and increased endothelial permeability. The latter was prevented by buffering [Ca2+]i with BAPTA, indicating that [Ca2+]i oscillations are crucial in the permeability changes. Bradykinin-triggered [Ca2+]i oscillations were inhibited by interfering with connexin channels, making use of carbenoxolone, Gap27, a peptide blocker of connexin channels, and Cx37/43 knockdown. Gap27 inhibition of the oscillations was rapid (within minutes) and work with connexin hemichannel-permeable dyes indicated hemichannel opening and purinergic signaling in response to stimulation with BK. Moreover, Gap27 inhibited the BK-triggered endothelial permeability increase in in vitro and in vivo experiments. By contrast, [Ca2+]i oscillations provoked by exposure to adenosine 5′ triphosphate (ATP) were not affected by carbenoxolone or Gap27 and ATP did not disturb endothelial permeability. We conclude that interfering with endothelial connexin hemichannels is a novel approach to limiting BBB-permeability alterations. PMID:21654699

A Cerebellar Framework for Predictive Coding and Homeostatic Regulation in Depressive Disorder.

PubMed

Schutter, Dennis J L G

2016-02-01

Depressive disorder is associated with abnormalities in the processing of reward and punishment signals and disturbances in homeostatic regulation. These abnormalities are proposed to impair error minimization routines for reducing uncertainty. Several lines of research point towards a role of the cerebellum in reward- and punishment-related predictive coding and homeostatic regulatory function in depressive disorder. Available functional and anatomical evidence suggests that in addition to the cortico-limbic networks, the cerebellum is part of the dysfunctional brain circuit in depressive disorder as well. It is proposed that impaired cerebellar function contributes to abnormalities in predictive coding and homeostatic dysregulation in depressive disorder. Further research on the role of the cerebellum in depressive disorder may further extend our knowledge on the functional and neural mechanisms of depressive disorder and development of novel antidepressant treatments strategies targeting the cerebellum.

Acute treatment with doxorubicin induced neurochemical impairment of the function of dopamine system in rat brain structures.

PubMed

Antkiewicz-Michaluk, Lucyna; Krzemieniecki, Krzysztof; Romanska, Irena; Michaluk, Jerzy; Krygowska-Wajs, Anna

2016-06-01

The clinical studies have shown that chemotherapy may impair cognitive functions especially in the patients treated for breast cancer. It should be mention that only few studies have made use of animals to investigate the effects of chemotherapy on the brain function. Doxorubicin (Adriamycin) is an anthracycline antibiotic commonly used for chemotherapy of breast cancer. This study examined the effect of doxorubicin (1.5 and 3.0mg/kg ip) after acute administration on the levels of dopamine, noradrenaline, serotonin and their metabolites in the rat brain structures connected with cognition and psychiatric disorders. The data indicate that doxorubicin produced a significant and specific for the dopamine system inhibition of its activity in the investigated structures connected with the fall of dopamine concentration (decrease from 25 to 30% in the frontal cortex; from 30 to 60% in the hippocampus and about 20% of the control in the striatum, p<0.05) and its extraneuronal metabolite, 3-MT (from 35% in the frontal cortex to 60% in the hippocampus of the control level, p<0.01). However, doxorubicin did not affect others monoaminergic transmitters in the brain: noradrenaline and serotonin. Summing up, these data indicate that a single injection of doxorubicin produced a clear and significant inhibition of dopamine system activity in all investigated structures with the strongest effect in the hippocampus what may lead to the disturbances of the cognitive functions at the patients treated for cancer. Moreover, such treatment did not significantly affect others monoaminergic transmitters such as noradrenaline and serotonin. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Imbalance in subregional connectivity of the right temporoparietal junction in major depression.

PubMed

Poeppl, Timm B; Müller, Veronika I; Hoffstaedter, Felix; Bzdok, Danilo; Laird, Angela R; Fox, Peter T; Langguth, Berthold; Rupprecht, Rainer; Sorg, Christian; Riedl, Valentin; Goya-Maldonado, Roberto; Gruber, Oliver; Eickhoff, Simon B

2016-08-01

Major depressive disorder (MDD) involves impairment in cognitive and interpersonal functioning. The right temporoparietal junction (RTPJ) is a key brain region subserving cognitive-attentional and social processes. Yet, findings on the involvement of the RTPJ in the pathophysiology of MDD have so far been controversial. Recent connectivity-based parcellation data revealed a topofunctional dualism within the RTPJ, linking its anterior and posterior part (aRTPJ/pRTPJ) to antagonistic brain networks for attentional and social processing, respectively. Comparing functional resting-state connectivity of the aRTPJ and pRTPJ in 72 MDD patients and 76 well-matched healthy controls, we found a seed (aRTPJ/pRTPJ) × diagnosis (MDD/controls) interaction in functional connectivity for eight regions. Employing meta-data from a large-scale neuroimaging database, functional characterization of these regions exhibiting differentially altered connectivity with the aRTPJ/pRTPJ revealed associations with cognitive (dorsolateral prefrontal cortex, parahippocampus) and behavioral (posterior medial frontal cortex) control, visuospatial processing (dorsal visual cortex), reward (subgenual anterior cingulate cortex, medial orbitofrontal cortex, posterior cingulate cortex), as well as memory retrieval and social cognition (precuneus). These findings suggest that an imbalance in connectivity of subregions, rather than disturbed connectivity of the RTPJ as a whole, characterizes the connectional disruption of the RTPJ in MDD. This imbalance may account for key symptoms of MDD in cognitive, emotional, and social domains. Hum Brain Mapp 37:2931-2942, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Abnormal Resting-State Functional Connectivity of the Anterior Cingulate Cortex in Unilateral Chronic Tinnitus Patients

PubMed Central

Chen, Yu-Chen; Liu, Shenghua; Lv, Han; Bo, Fan; Feng, Yuan; Chen, Huiyou; Xu, Jin-Jing; Yin, Xindao; Wang, Shukui; Gu, Jian-Ping

2018-01-01

Purpose: The anterior cingulate cortex (ACC) has been suggested to be involved in chronic subjective tinnitus. Tinnitus may arise from aberrant functional coupling between the ACC and cerebral cortex. To explore this hypothesis, we used resting-state functional magnetic resonance imaging (fMRI) to illuminate the functional connectivity (FC) network of the ACC subregions in chronic tinnitus patients. Methods: Resting-state fMRI scans were obtained from 31 chronic right-sided tinnitus patients and 40 healthy controls (age, sex, and education well-matched) in this study. Rostral ACC and dorsal ACC were selected as seed regions to investigate the intrinsic FC with the whole brain. The resulting FC patterns were correlated with clinical tinnitus characteristics including the tinnitus duration and tinnitus distress. Results: Compared with healthy controls, chronic tinnitus patients showed disrupted FC patterns of ACC within several brain networks, including the auditory cortex, prefrontal cortex, visual cortex, and default mode network (DMN). The Tinnitus Handicap Questionnaires (THQ) scores showed positive correlations with increased FC between the rostral ACC and left precuneus (r = 0.507, p = 0.008) as well as the dorsal ACC and right inferior parietal lobe (r = 0.447, p = 0.022). Conclusions: Chronic tinnitus patients have abnormal FC networks originating from ACC to other selected brain regions that are associated with specific tinnitus characteristics. Resting-state ACC-cortical FC disturbances may play an important role in neuropathological features underlying chronic tinnitus. PMID:29410609

The Importance of Neurogenic Inflammation in Blast-Induced Neurotrauma

DTIC Science & Technology

2013-01-01

mild/moderate BINT are imaged by magnetic resonance imaging ( MRI ) to visualize potential macrophage infiltration; blood-brain barrier (BBB) disturbance...TERMS blast, traumatic brain injury, brain, inflammation, magnetic resonance imaging , mice 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...monitoring the success of therapeutic interventions. In this annual report we have utilized current live imaging methods (i.e. magnetic resonance

Chapter 36: history of aphasia: from brain to language.

PubMed

Eling, Paul; Whitaker, Harry

2010-01-01

An historical overview is presented that focuses on the changes both in approach and topics with respect to language disturbances due to brain lesions. Early cases of language disorders were described without any theorizing about language or its relation to the brain. Also, three forms of speech disorder were distinguished: traulotes, psellotes and ischophonia, which are only marginally related to aphasia. In the 18th century some authors, in particular Gesner and Crichton, attempted to explain language disorders in terms of mental processes. The great debate on both the anatomical (Broca, Wernicke) and functional (Wernicke, Lichtheim) aspects of aphasia dominated late 19th century discussion of localization of function, leading to the development of what we now call the cognitive neurosciences. In this period, language processing was described in terms of a simple functional model of word recognition and production; linguistic principles played no role. At the beginning of the 20th century the discussion on language disorders waned due to a decrease of interest in the issue of localization; aphasia became primarily a clinical issue of how best to classify patients. In the second half of the 20th century, the field of aphasia developed rapidly due to studies performed at the Boston Aphasia Unit and, more importantly, to a change of orientation to linguistic notions of language structure, as introduced by Chomsky.

Reduced fiber integrity and cognitive control in adolescents with internet gaming disorder.

PubMed

Xing, Lihong; Yuan, Kai; Bi, Yanzhi; Yin, Junsen; Cai, Chenxi; Feng, Dan; Li, Yangding; Song, Min; Wang, Hongmei; Yu, Dahua; Xue, Ting; Jin, Chenwang; Qin, Wei; Tian, Jie

2014-10-24

The association between the impaired cognitive control and brain regional abnormalities in Internet gaming disorder (IGD) adolescents had been validated in numerous studies. However, few studies focused on the role of the salience network (SN), which regulates dynamic communication among brain core neurocognitive networks to modulate cognitive control. Seventeen IGD adolescents and 17 healthy controls participated in the study. By combining resting-state functional connectivity and diffusion tensor imaging (DTI) tractography methods, we examined the changes of functional and structural connections within SN in IGD adolescents. The color-word Stroop task was employed to assess the impaired cognitive control in IGD adolescents. Correlation analysis was carried out to investigate the relationship between the neuroimaging indices and behavior performance in IGD adolescents. The impaired cognitive control in IGD was validated by more errors during the incongruent condition in color-word Stroop task. The right SN tract showed the decreased fractional anisotropy (FA) in IGD adolescents, though no significant differences of functional connectivity were detected. Moreover, the FA values of the right SN tract were negatively correlated with the errors during the incongruent condition in IGD adolescents. Our results revealed the disturbed structural connectivity within SN in IGD adolescents, which may be related with impaired cognitive control. It is hoped that the brain-behavior relationship from network perspective may enhance the understanding of IGD. Copyright © 2014 Elsevier B.V. All rights reserved.

The Significance of Brain Transcranial Sonography in Burning Mouth Syndrome: a Pilot Study.

PubMed

Zavoreo, Iris; Vučićević, Vanja; Boras; Zadravec, Dijana; Bašić, Vanja; Kes; Ciliga, Dubravka; Gabrić, Dragana

2017-03-01

Burning mouth syndrome (BMS) is a chronic disorder which is affecting mostly postmenopausal women and is characterized by burning symptoms in the oral cavity on the clinically healthy oral mucosa. Also, the results of previous studies suggested a possible role of peripheral and/or central neurological disturbances in these patients. The aim of this study was to analyze patients with burning mouth syndrome using transcranial sonography. By use of transcranial sonography of the brain parenchyma, substantia nigra , midbrain raphe and brain nucleus were evaluated in 20 patients with BMS (64.7±12.3 years) and 20 controls with chronic pain in the lumbosacral region (61.5±15). Statistical analysis was performed by use of Student t test with significance set at p<0.05. The results of this study have shown hypoechogenicity of the substantia nigra and midbrain raphe as well as hyperechogenicity of the brain nucleus in BMS patients (p<0,05) as compared to controls. Altered transcranial sonography findings of the brain parenchyma , midbrain raphe and brain nucl eus in patients with burning mouth syndrome might reflect central disturbances within this syndrome. Burning Mouth Syndrome; Transcranial Sonography; substantia nigra; Midbrain Raphe Nuclei; Red Nucleus.

DNA Repair Modulates The Vulnerability of The Developing Brain to Alkylating Agents

PubMed Central

Kisby, G.E.; Olivas, A.; Park, T.; Churchwell, M.; Doerge, D.; Samson, L. D.; Gerson, S.L.; Turker, M.S.

2009-01-01

Neurons of the developing brain are especially vulnerable to environmental agents that damage DNA (i.e., genotoxicants), but the mechanism is poorly understood. The focus of the present study is to demonstrate that DNA damage plays a key role in disrupting neurodevelopment. To examine this hypothesis, we compared the cytotoxic and DNA damaging properties of the methylating agents methylazoxymethanol (MAM) and dimethyl sulfate (DMS) and the mono- and bifunctional alkylating agents chloroethylamine (CEA) and nitrogen mustard (HN2), in granule cell neurons derived from the cerebellum of neonatal wild type mice and three transgenic DNA repair strains. Wild type cerebellar neurons were significantly more sensitive to the alkylating agents DMS and HN2 than neuronal cultures treated with MAM or the half-mustard CEA. Parallel studies with neuronal cultures from mice deficient in alkylguanine DNA glycosylase (Aag-/-) or O6-methylguanine methyltransferase (Mgmt-/-), revealed significant differences in the sensitivity of neurons to all four genotoxicants. Mgmt-/- neurons were more sensitive to MAM and HN2 than the other genotoxicants and wild type neurons treated with either alkylating agent. In contrast, Aag-/- neurons were for the most part significantly less sensitive than wild type or Mgmt-/- neurons to MAM and HN2. Aag-/- neurons were also significantly less sensitive than wild type neurons treated with either DMS or CEA. Granule cell development and motor function were also more severely disturbed by MAM and HN2 in Mgmt-/- mice than in comparably treated wild type mice. In contrast, cerebellar development and motor function were well preserved in MAM treated Aag-/- or MGMT overexpressing (MgmtTg+) mice, even as compared with wild type mice suggesting that AAG protein increases MAM toxicity, whereas MGMT protein decreases toxicity. Surprisingly, neuronal development and motor function were severely disturbed in MgmtTg+ mice treated with HN2. Collectively, these in vitro and in vivo studies demonstrate that the type of DNA lesion and the efficiency of DNA repair are two important factors that determine the vulnerability of the developing brain to long-term injury by a genotoxicant. PMID:19162564

Psychosomatic Disorders and Mental Retardation in Children. The Langley Porter Child Psychiatry Series, Volume 3.

ERIC Educational Resources Information Center

Szurek, S.A.; Berlin, I.N.

The reciprocal relationship between the child's emotional state and physiological disturbances is explored, and the effect of emotional disturbance on varieties of mental retardation or on obvious brain damage resulting from genetic metabolic disorders is assessed. Psychosomatic disorders of childhood are discussed in six papers on genetic…

Role of Microglia Disturbances and Immune-Related Marker Abnormalities in Cortical Circuitry Dysfunction in Schizophrenia

PubMed Central

Volk, David W.

2017-01-01

Studies of genetics, serum cytokines, and autoimmune illnesses suggest that immune-related abnormalities are involved in the disease process of schizophrenia. Furthermore, direct evidence of cortical immune activation, including markedly elevated levels of many immune-related markers, have been reported in the prefrontal cortex in multiple cohorts of schizophrenia subjects. Within the prefrontal cortex in schizophrenia, deficits in the basilar dendritic spines of layer 3 pyramidal neurons and disturbances in inhibitory inputs to pyramidal neurons have also been commonly reported. Interestingly, microglia, the resident immune-related cells of the brain, also regulate excitatory and inhibitory input to pyramidal neurons. Consequently, in this review, we describe the cytological and molecular evidence of immune activation that has been reported in the brains of individuals with schizophrenia and the potential links between these immune-related disturbances with previously reported disturbances in pyramidal and inhibitory neurons in the disorder. Finally, we discuss the role that activated microglia may play in connecting these observations and as potential therapeutic treatment targets in schizophrenia. PMID:28007586

Repetitive traumatic brain injury (or concussion) increases severity of sleep disturbance among deployed military personnel.

PubMed

Bryan, Craig J

2013-06-01

Considerable research indicates that sleep disturbances and insomnia are more common and severe among individuals following a traumatic brain injury (TBI). It remains unclear, however, how the experience of multiple TBIs affect sleep disturbances and insomnia. The current study investigated the incidence and severity of insomnia and sleep complaints among active-duty military personnel who have sustained multiple TBIs. Upon intake at a military TBI clinic located in Iraq, 150 male military patients completed standardized self-report measures and clinical interviews. Patients were categorized into three groups according to history of TBI: zero TBIs (n = 18), single TBI (n = 54), multiple TBIs (n = 78). Rates of clinical insomnia significantly increased across TBI groups (P < 0.001):- 5.6% for no TBIs, 20.4% for single TBI, and 50.0% for multiple TBIs. Insomnia severity significantly increased across TBI groups even when controlling for depression, posttraumatic stress disorder, and concussion symptom severity (B = 1.134, standard error = 0.577, P = 0.049). Multiple TBIs are associated with increased risk for and severity of sleep disturbance among male military personnel.

The impacts of acute carbon monoxide poisoning on the brain: Longitudinal clinical and 99mTc ethyl cysteinate brain SPECT characterization of patients with persistent and delayed neurological sequelae.

PubMed

Tsai, Chung-Fen; Yip, Ping-Keung; Chen, Shao-Yuan; Lin, Jen-Cheng; Yeh, Zai-Ting; Kung, Lan-Yu; Wang, Cheng-Yi; Fan, Yu-Ming

2014-04-01

Acute carbon monoxide (CO) poisoning poses a significant threat to the central nervous system. It can cause brain injury and diverse neurological deficits including persistent neurological sequelae (PNS) and delayed neurological sequelae (DNS). The study aimed to investigate the long-term impacts of acute CO poisoning on brain perfusion and neurological function, and to explore potential differences between PNS and DNS patients. We evaluated brain perfusion using (99m)Tc ethyl cysteinate (ECD) brain single photon emission computed tomography (SPECT) and assessed clinical neurological symptoms and signs one month following acute poisoning. For DNS patients, ECD SPECT and clinical evaluation were performed when their delayed symptoms appeared. All patients had follow-up SPECT imaging, along with clinical assessments six months following poisoning. 12 PNS and 12 DNS patients were recruited between 2007 and 2010. Clinically, the main characteristic presentations were cognitive decline, emotional instability, and gait disturbance. SPECT imaging demonstrated consistent frontal hypoperfusion of varying severities in all patients, which decreased in severity at follow-up imaging. DNS patients usually had more severe symptoms and perfusion defects, along with worse clinical outcomes than the PNS group. These results suggest that acute CO poisoning might lead to long term brain injuries and neurological sequelae, particularly in DNS patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Preclinical Models of Traumatic Brain Injury: Emerging Role of Glutamate in the Pathophysiology of Depression.

PubMed

O'Neil, Darik A; Nicholas, Melissa A; Lajud, Naima; Kline, Anthony E; Bondi, Corina O

2018-01-01

More than 10 million people worldwide incur a traumatic brain injury (TBI) each year, with two million cases occurring in the United States. TBI survivors exhibit long-lasting cognitive and affective sequelae that are associated with reduced quality of life and work productivity, as well as mental and emotional disturbances. While TBI-related disabilities often manifest physically and conspicuously, TBI has been linked with a "silent epidemic" of psychological disorders, including major depressive disorder (MDD). The prevalence of MDD post-insult is approximately 50% within the 1st year. Furthermore, given they are often under-reported when mild, TBIs could be a significant overall cause of MDD in the United States. The emergence of MDD post-TBI may be rooted in widespread disturbances in the modulatory role of glutamate, such that glutamatergic signaling becomes excessive and deleterious to neuronal integrity, as reported in both clinical and preclinical studies. Following this acute glutamatergic storm, regulators of glutamatergic function undergo various manipulations, which include, but are not limited to, alterations in glutamatergic subunit composition, release, and reuptake. This review will characterize the glutamatergic functional and signaling changes that emerge and persist following experimental TBI, utilizing evidence from clinical, molecular, and rodent behavioral investigations. Special care will be taken to speculate on how these manipulations may correlate with the development of MDD following injury in the clinic, as well as pharmacotherapies to date. Indisputably, TBI is a significant healthcare issue that warrants discovery and subsequent refinement of therapeutic strategies to improve neurobehavioral recovery and mental health.

Pathophysiological Bases of Comorbidity: Traumatic Brain Injury and Post-Traumatic Stress Disorder.

PubMed

Kaplan, Gary B; Leite-Morris, Kimberly A; Wang, Lei; Rumbika, Kendra K; Heinrichs, Stephen C; Zeng, Xiang; Wu, Liquan; Arena, Danielle T; Teng, Yang D

2018-01-15

The high rates of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) diagnoses encountered in recent years by the United States Veterans Affairs Healthcare System have increased public awareness and research investigation into these conditions. In this review, we analyze the neural mechanisms underlying the TBI/PTSD comorbidity. TBI and PTSD present with common neuropsychiatric symptoms including anxiety, irritability, insomnia, personality changes, and memory problems, and this overlap complicates diagnostic differentiation. Interestingly, both TBI and PTSD can be produced by overlapping pathophysiological changes that disrupt neural connections termed the "connectome." The neural disruptions shared by PTSD and TBI and the comorbid condition include asymmetrical white matter tract abnormalities and gray matter changes in the basolateral amygdala, hippocampus, and prefrontal cortex. These neural circuitry dysfunctions result in behavioral changes that include executive function and memory impairments, fear retention, fear extinction deficiencies, and other disturbances. Pathophysiological etiologies can be identified using experimental models of TBI, such as fluid percussion or blast injuries, and for PTSD, using models of fear conditioning, retention, and extinction. In both TBI and PTSD, there are discernible signs of neuroinflammation, excitotoxicity, and oxidative damage. These disturbances produce neuronal death and degeneration, axonal injury, and dendritic spine dysregulation and changes in neuronal morphology. In laboratory studies, various forms of pharmacological or psychological treatments are capable of reversing these detrimental processes and promoting axonal repair, dendritic remodeling, and neurocircuitry reorganization, resulting in behavioral and cognitive functional enhancements. Based on these mechanisms, novel neurorestorative therapeutics using anti-inflammatory, antioxidant, and anticonvulsant agents may promote better outcomes for comorbid TBI and PTSD.

Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats.

PubMed

Partearroyo, Teresa; Pérez-Miguelsanz, Juliana; Peña-Melián, Ángel; Maestro-de-Las-Casas, Carmen; Úbeda, Natalia; Varela-Moreiras, Gregorio

2016-06-01

The brain is particularly sensitive to folate metabolic disturbances, because methyl groups are critical for brain functions. This study aimed to investigate the effects of different dietary levels of folic acid (FA) on postnatal cerebellar morphology, including the architecture and organisation of the various layers. A total of forty male OFA rats (a Sprague-Dawley strain), 5 weeks old, were classified into the following four dietary groups: FA deficient (0 mg/kg FA); FA supplemented (8 mg/kg FA); FA supra-supplemented (40 mg/kg FA); and control (2 mg/kg FA) (all n 10 per group). Rats were fed ad libitum for 30 d. The cerebellum was quickly removed and processed for histological and immunohistochemical analysis. Slides were immunostained for glial fibrillary acidic protein (to label Bergmann glia), calbindin (to label Purkinje cells) and NeuN (to label post-mitotic neurons). Microscopic analysis revealed two types of defect: partial disappearance of fissures and/or neuronal ectopia, primarily in supra-supplemented animals (incidence of 80 %, P≤0·01), but also in deficient and supplemented groups (incidence of 40 %, P≤0·05), compared with control animals. The primary fissure was predominantly affected, sometimes accompanied by defects in the secondary fissure. Our findings show that growing rats fed an FA-modified diet, including both deficient and supplemented diets, have an increased risk of disturbances in cerebellar corticogenesis. Defects caused by these diets may have functional consequences in later life. The present study is the first to demonstrate that cerebellar morphological defects can arise from deficient, as well as high, FA levels in the diet.

Functional neuroimaging in epileptic encephalopathies.

PubMed

Siniatchkin, Michael; Capovilla, Giuseppe

2013-11-01

Epileptic encephalopathies (EEs) represent a group of severe epileptic disorders associated with cognitive and behavioral disturbances. The mechanisms of cognitive disability in EEs remain unclear. This review summarized neuroimaging studies that have tried to describe specific fingerprints of brain activation in EE. Although the epileptic activity can be generated individually in different brain regions, it seems likely that the activity propagates in a syndrome-specific way. In some EEs, the epileptiform discharges were associated with an interruption of activity in the default mode network. In another EE, other mechanisms seem to underlie cognitive disability associated with epileptic activity, for example, abnormal connectivity pattern or interfering activity in the thalamocortical network. Further neuroimaging studies are needed to investigate the short-term and long-term impact of epileptic activity on cognition and development. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Cortical excitability and neurology: insights into the pathophysiology

PubMed Central

Badawy, Radwa A.B.; Loetscher, Tobias; Macdonell, Richard A.L.; Brodtmann, Amy

2012-01-01

Summary Transcranial magnetic stimulation (TMS) is a technique developed to non-invasively investigate the integrity of human motor corticospinal tracts. Over the last three decades, the use of stimulation paradigms including single-pulse TMS, paired-pulse TMS, repetitive TMS, and integration with EEG and functional imaging have been developed to facilitate measurement of cortical excitability. Through the use of these protocols, TMS has evolved into an excellent tool for measuring cortical excitability. TMS has high sensitivity in detecting subtle changes in cortical excitability, and therefore it is also a good measure of disturbances associated with brain disorders. In this review, we appraise the current literature on cortical excitability studies using TMS in neurological disorders. We begin with a brief overview of current TMS measures and then show how these have added to our understanding of the underlying mechanisms of brain disorders. PMID:23402674

Vegetarian diet and excessive tea consumption: a dangerous association?

PubMed

Fiacco, Fabrizio; Barbato, Luca; Pecoraro, Maria Giovanna; Maggio, Paola

2017-02-01

Rare metabolic diseases may sometimes arise acutely and endanger human life if not immediately recognized and treated. Marchiafava Bignami disease is an uncommon neurologic disorder described in alcohol abusers and characterized by an acute severe damage of brain white matter. Even more rarely, it has been reported in non-alcohol addicted patients, but never in vegetarian people. This is a case report of a young vegetarian woman, accustomed to drink high amounts of tea, who, three weeks after her first natural childbirth, developed serious motor and cognitive disturbances. A timely brain magnetic resonance (MR) allowed us to identify Marchiafava Bignami disease and she healed few hours after the administration of parenteral steroids and vitamins. We advise to suspect Marchiafava Bignami Disease in all patients presenting with non-obvious acute generalized motor and cognitive disturbances, also if non alcoholics, and to collect the nutritional habits in all patients with suspected symptoms. In these cases a timely brain MRI is warranted, since brain imaging is typical and patients may recover after a prompt treatment.

Sequential social experiences interact to modulate aggression but not brain gene expression in the honey bee (Apis mellifera).

PubMed

Rittschof, Clare C

2017-01-01

In highly structured societies, individuals behave flexibly and cooperatively in order to achieve a particular group-level outcome. However, even in social species, environmental inputs can have long lasting effects on individual behavior, and variable experiences can even result in consistent individual differences and constrained behavioral flexibility. Despite the fact that such constraints on behavior could have implications for behavioral optimization at the social group level, few studies have explored how social experiences accumulate over time, and the mechanistic basis of these effects. In the current study, I evaluate how sequential social experiences affect individual and group level aggressive phenotypes, and individual brain gene expression, in the highly social honey bee ( Apis mellifera ). To do this, I combine a whole colony chronic predator disturbance treatment with a lab-based manipulation of social group composition. Compared to the undisturbed control, chronically disturbed individuals show lower aggression levels overall, but also enhanced behavioral flexibility in the second, lab-based social context. Disturbed bees display aggression levels that decline with increasing numbers of more aggressive, undisturbed group members. However, group level aggressive phenotypes are similar regardless of the behavioral tendencies of the individuals that make up the group, suggesting a combination of underlying behavioral tendency and negative social feedback influences the aggressive behaviors displayed, particularly in the case of disturbed individuals. An analysis of brain gene expression showed that aggression related biomarker genes reflect an individual's disturbance history, but not subsequent social group experience or behavioral outcomes. In highly social animals with collective behavioral phenotypes, social context may mask underlying variation in individual behavioral tendencies. Moreover, gene expression patterns may reflect behavioral tendency, while behavioral outcomes are further regulated by social cues perceived in real-time.

Neuronal Type-Specific Gene Expression Profiling and Laser-Capture Microdissection

PubMed Central

Pietersen, Charmaine Y.; Lim, Maribel P.; Macey, Laurel; Woo, Tsung-Ung W.; Sonntag, Kai C.

2014-01-01

The human brain is an exceptionally heterogeneous structure. In order to gain insight into the neurobiological basis of neural circuit disturbances in various neurologic or psychiatric diseases, it is often important to define the molecular cascades that are associated with these disturbances in a neuronal type-specific manner. This can be achieved by the use of laser microdissection, in combination with molecular techniques such as gene expression profiling. To identify neurons in human postmortem brain tissue, one can use the inherent properties of the neuron, such as pigmentation and morphology or its structural composition through immunohistochemistry (IHC). Here, we describe the isolation of homogeneous neuronal cells and high-quality RNA from human postmortem brain material using a combination of rapid IHC, Nissl staining, or simple morphology with Laser-Capture Microdissection (LCM) or Laser Microdissection (LMD). PMID:21761317

Neuronal type-specific gene expression profiling and laser-capture microdissection.

PubMed

Pietersen, Charmaine Y; Lim, Maribel P; Macey, Laurel; Woo, Tsung-Ung W; Sonntag, Kai C

2011-01-01

The human brain is an exceptionally heterogeneous structure. In order to gain insight into the neurobiological basis of neural circuit disturbances in various neurologic or psychiatric diseases, it is often important to define the molecular cascades that are associated with these disturbances in a neuronal type-specific manner. This can be achieved by the use of laser microdissection, in combination with molecular techniques such as gene expression profiling. To identify neurons in human postmortem brain tissue, one can use the inherent properties of the neuron, such as pigmentation and morphology or its structural composition through immunohistochemistry (IHC). Here, we describe the isolation of homogeneous neuronal cells and high-quality RNA from human postmortem brain material using a combination of rapid IHC, Nissl staining, or simple morphology with Laser-Capture Microdissection (LCM) or Laser Microdissection (LMD).

Brain corticostriatal systems and the major clinical symptom dimensions of obsessive-compulsive disorder.

PubMed

Harrison, Ben J; Pujol, Jesus; Cardoner, Narcis; Deus, Joan; Alonso, Pino; López-Solà, Marina; Contreras-Rodríguez, Oren; Real, Eva; Segalàs, Cinto; Blanco-Hinojo, Laura; Menchon, José M; Soriano-Mas, Carles

2013-02-15

Functional neuroimaging studies have provided consistent support for the idea that obsessive-compulsive disorder (OCD) is associated with disturbances of brain corticostriatal systems. However, in general, these studies have not sought to account for the disorder's prominent clinical heterogeneity. To address these concerns, we investigated the influence of major OCD symptom dimensions on brain corticostriatal functional systems in a large sample of OCD patients (n = 74) and control participants (n = 74) examined with resting-state functional magnetic resonance imaging. We employed a valid method for mapping ventral and dorsal striatal functional connectivity, which supported both standard group comparisons and linear regression analyses with patients' scores on the Dimensional Yale-Brown Obsessive-Compulsive Scale. Consistent with past findings, patients demonstrated a common connectivity alteration involving the ventral striatum and orbitofrontal cortex that predicted overall illness severity levels. This common alteration was independent of the effect of particular symptom dimensions. Instead, we observed distinct anatomical relationships between the severity of symptom dimensions and striatal functional connectivity. Aggression symptoms modulated connectivity between the ventral striatum, amygdala, and ventromedial frontal cortex, while sexual/religious symptoms had a specific influence on ventral striatal-insular connectivity. Hoarding modulated the strength of ventral and dorsal striatal connectivity with distributed frontal regions. Taken together, these results suggest that pathophysiological changes among orbitofrontal-striatal regions may be common to all forms of OCD. They suggest that a further examination of certain dimensional relationships will also be relevant for advancing current neurobiological models of the disorder. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Nausea as a sentinel symptom for cytotoxic chemotherapy effects on the gut-brain axis among women receiving treatment for recurrent ovarian cancer: an exploratory analysis.

PubMed

Donovan, Heidi S; Hagan, Teresa L; Campbell, Grace B; Boisen, Michelle M; Rosenblum, Leah M; Edwards, Robert P; Bovbjerg, Dana H; Horn, Charles C

2016-06-01

Nausea is a common and potentially serious effect of cytotoxic chemotherapy for recurrent ovarian cancer and may function as a sentinel symptom reflecting adverse effects on the gut-brain axis (GBA) more generally, but research is scant. As a first exploratory test of this GBA hypothesis, we compared women reporting nausea to women not reporting nausea with regard to the severity of other commonly reported symptoms in this patient population. A secondary analysis of data systematically collected from women in active chemotherapy treatment for recurrent ovarian cancer (n = 158) was conducted. The Symptom Representation Questionnaire (SRQ) provided severity ratings for 22 common symptoms related to cancer and chemotherapy. Independent sample t tests and regression analyses were used to compare women with and without nausea with regard to their experience of other symptoms. Nausea was reported by 89 (56.2 %) women. Symptoms that were significantly associated with nausea in bivariate and regression analyses included abdominal bloating, bowel disturbances, dizziness, depression, drowsiness, fatigue, headache, lack of appetite, memory problems, mood swings, shortness of breath, pain, sleep disturbance, urinary problems, vomiting, and weight loss. Symptoms that were not associated with nausea included hair loss, numbness and tingling, sexuality concerns, and weight gain. Nausea experienced during chemotherapy for recurrent ovarian cancer may be an indicator of broader effects on the gut-brain axis. A better understanding of the mechanisms underlying these effects could lead to the development of novel supportive therapies to increase the tolerability and effectiveness of cancer treatment.

Schizophrenia and the neurodevelopmental continuum:evidence from genomics

PubMed Central

Owen, Michael J.; O'Donovan, Michael C.

2017-01-01

The idea that disturbances occurring early in brain development contribute to the pathogenesis of schizophrenia, often referred to as the neurodevelopmental hypothesis, has become widely accepted. Despite this, the disorder is viewed as being distinct nosologically, and by implication pathophysiologically and clinically, from syndromes such as autism spectrum disorders, attention‐deficit/hyperactivity disorder (ADHD) and intellectual disability, which typically present in childhood and are grouped together as “neurodevelopmental disorders”. An alternative view is that neurodevelopmental disorders, including schizophrenia, rather than being etiologically discrete entities, are better conceptualized as lying on an etiological and neurodevelopmental continuum, with the major clinical syndromes reflecting the severity, timing and predominant pattern of abnormal brain development and resulting functional abnormalities. It has also been suggested that, within the neurodevelopmental continuum, severe mental illnesses occupy a gradient of decreasing neurodevelopmental impairment as follows: intellectual disability, autism spectrum disorders, ADHD, schizophrenia and bipolar disorder. Recent genomic studies have identified large numbers of specific risk DNA changes and offer a direct and robust test of the predictions of the neurodevelopmental continuum model and gradient hypothesis. These findings are reviewed in detail. They not only support the view that schizophrenia is a disorder whose origins lie in disturbances of brain development, but also that it shares genetic risk and pathogenic mechanisms with the early onset neurodevelopmental disorders (intellectual disability, autism spectrum disorders and ADHD). They also support the idea that these disorders lie on a gradient of severity, implying that they differ to some extent quantitatively as well as qualitatively. These findings have important implications for nosology, clinical practice and research. PMID:28941101

Schizophrenia and the neurodevelopmental continuum:evidence from genomics.

PubMed

Owen, Michael J; O'Donovan, Michael C

2017-10-01

The idea that disturbances occurring early in brain development contribute to the pathogenesis of schizophrenia, often referred to as the neurodevelopmental hypothesis, has become widely accepted. Despite this, the disorder is viewed as being distinct nosologically, and by implication pathophysiologically and clinically, from syndromes such as autism spectrum disorders, attention-deficit/hyperactivity disorder (ADHD) and intellectual disability, which typically present in childhood and are grouped together as "neurodevelopmental disorders". An alternative view is that neurodevelopmental disorders, including schizophrenia, rather than being etiologically discrete entities, are better conceptualized as lying on an etiological and neurodevelopmental continuum, with the major clinical syndromes reflecting the severity, timing and predominant pattern of abnormal brain development and resulting functional abnormalities. It has also been suggested that, within the neurodevelopmental continuum, severe mental illnesses occupy a gradient of decreasing neurodevelopmental impairment as follows: intellectual disability, autism spectrum disorders, ADHD, schizophrenia and bipolar disorder. Recent genomic studies have identified large numbers of specific risk DNA changes and offer a direct and robust test of the predictions of the neurodevelopmental continuum model and gradient hypothesis. These findings are reviewed in detail. They not only support the view that schizophrenia is a disorder whose origins lie in disturbances of brain development, but also that it shares genetic risk and pathogenic mechanisms with the early onset neurodevelopmental disorders (intellectual disability, autism spectrum disorders and ADHD). They also support the idea that these disorders lie on a gradient of severity, implying that they differ to some extent quantitatively as well as qualitatively. These findings have important implications for nosology, clinical practice and research. © 2017 World Psychiatric Association.

[A case of glioblastoma multiforme which indicated the early stage on brain MRI].

PubMed

Ono, K; Tohma, Y; Yoshida, M; Takamori, M

2000-04-01

A 57-year-old male was urgently carried to our hospital because of sudden loss of consciousness, lasting about 10 minutes. He had resumed consciousness before he arrived at our hospital. Neurologically, he had mild muscle weakness of the right arm. Deep tendon reflexes in the right upper extremity were reduced. In high level functions, speech disturbance, dysgraphia (disturbed ability to write Hiragana), and constructive apraxia were noted. A brain MRI upon admission showed a poorly demarcated, high signal intensity area in the cortical and subcortical layers of the left temporal and parietal lobes. This was visible on T 2 weighted images(T 2 WI), although no abnormalities were visible on T 1 weighted images(T 1 WI). No contrast enhancement was effected by Gd-DTPA. The patient was therefore suspected of having a tumor or degenerative disease and was monitored closely. About 4 months later after onset, his symptoms became aggravated, and brain MRI disclosed a marked low signal intensity area on T 1 WI and a heterogeneous high signal intensity area on T 2 WI. The abnormal signal intensity area was surrounded by extensive edema and mass effect. Ring-shaped, irregular, contrast enhanced areas were also visible. Cerebral angiography revealed a poorly demarcated tumor stain in the area supplied by the middle cerebral artery. The tumor was removed surgically and was histopathologically rated as glioblastoma multiforme(GBM). Because this case represents a valuable example of early stage of GBM, it will be discussed in this paper, along with differential diagnoses.

Is blue light, cryptochrome in the eye, and magnetite in the brain involved in the development of frontotemporal dementia and other diseases?

PubMed

Størmer, Fredrik C

2015-04-01

When cryptochrome in the retina is exposed to blue light, it undergo series of complicated chemical reactions. One of these intermediates has magnetic properties. It could be a link between the magnetic stage of cryptochrome in the retina and magnetite in the brain. A disturbance in this system could be involved in the development of frontotemporal dementia and other mental disturbances like Alzheimer's disease. There could also be a link between circadian rhythms and memory dysfunction connected to schizophrenia, type 2 diabetes, and blue light. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice

PubMed Central

Umemura, Mariko; Ogura, Tae; Matsuzaki, Ayako; Nakano, Haruo; Takao, Keizo; Miyakawa, Tsuyoshi; Takahashi, Yuji

2017-01-01

Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/-) mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders. PMID:28744205

Disturbed vesicular trafficking of membrane proteins in prion disease.

PubMed

Uchiyama, Keiji; Miyata, Hironori; Sakaguchi, Suehiro

2013-01-01

The pathogenic mechanism of prion diseases remains unknown. We recently reported that prion infection disturbs post-Golgi trafficking of certain types of membrane proteins to the cell surface, resulting in reduced surface expression of membrane proteins and abrogating the signal from the proteins. The surface expression of the membrane proteins was reduced in the brains of mice inoculated with prions, well before abnormal symptoms became evident. Prions or pathogenic prion proteins were mainly detected in endosomal compartments, being particularly abundant in recycling endosomes. Some newly synthesized membrane proteins are delivered to the surface from the Golgi apparatus through recycling endosomes, and some endocytosed membrane proteins are delivered back to the surface through recycling endosomes. These results suggest that prions might cause neuronal dysfunctions and cell loss by disturbing post-Golgi trafficking of membrane proteins via accumulation in recycling endosomes. Interestingly, it was recently shown that delivery of a calcium channel protein to the cell surface was impaired and its function was abrogated in a mouse model of hereditary prion disease. Taken together, these results suggest that impaired delivery of membrane proteins to the cell surface is a common pathogenic event in acquired and hereditary prion diseases.

CHEMICALS THAT DISRUPT THE THYROID AXIS: COLLABORATION BETWEEN ORD AND STAR GRANT RECIPIENTS.

EPA Science Inventory

For effective regulation, the EPA must determine the potential adverse consequences of mild disturbances of the thyroid axis on brain development. Severe hypothyroidism has long been known to lead to profound alterations in brain development and mental retardation. However, the s...

[Alcohol brain disease: systematization of metalcohol psychoses].

PubMed

Sivolap, Iu P

2006-01-01

Based on the own clinical observations, the author analyzes pathogenetic hypotheses and contemporary typology of metalcohol psychoses, proposes a concept of alcohol brain disease, including typical and atypical forms. It is suggested that typical forms rest on specific neurometabolic disturbances while the constitutional predisposition plays a main role in the forming of atypical variants. The principles of effective treatment of alcohol brain disease are considered.

Influence of metformin on mitochondrial subproteome in the brain of apoE knockout mice.

PubMed

Suski, Maciej; Olszanecki, Rafał; Chmura, Łukasz; Stachowicz, Aneta; Madej, Józef; Okoń, Krzysztof; Adamek, Dariusz; Korbut, Ryszard

2016-02-05

Neurodegenerative diseases are the set of progressive, age-related brain disorders, characterized by an excessive accumulation of mutant proteins in the certain regions of the brain. Such changes, collectively identified as causal factors of neurodegeneration, all impact mitochondria, imminently leading to their dysfunction. These observations predestine mitochondria as an attractive drug target for counteracting degenerative brain damage. The aim of this study was to use a differential proteomic approach to comprehensively assess the changes in mitochondrial protein expression in the brain of apoE-knockout mice (apoE(-/-)) and to investigate the influence of prolonged treatment with metformin - an indirect activator of AMP-activated protein kinase (AMPK) on the brain mitoproteome in apoE(-/-) mice. The quantitative assessment of the brain mitoproteome in apoE(-/-) revealed the changes in 10 proteins expression as compared to healthy C57BL/6J mice and 25 proteins expression in metformin-treated apoE(-/-) mice. Identified proteins mainly included apoptosis regulators, metabolic enzymes and structural proteins. In summary, our study provided proteomic characteristics suggesting the decrease of antioxidant defense and structural disturbances in the brain mitochondria of apoE(-/-) mice as compared to healthy controls. In this setting, the use of metformin changed the expression of several proteins primarily involved in metabolic processes, the regulation of apoptosis and the structural maintenance of mitochondria, what could potentially restore their native functionalities. Copyright © 2015 Elsevier B.V. All rights reserved.

Cerebellar Alterations and Gait Defects as Therapeutic Outcome Measures for Enzyme Replacement Therapy in α-Mannosidosis

PubMed Central

Damme, Markus; Stroobants, Stijn; Walkley, Steven U.; Lüllmann-Rauch, Renate; D`Hooge, Rudi; Fogh, Jens; Saftig, Paul; Lübke, Torben; Blanz, Judith

2011-01-01

α-Mannosidosis is a rare lysosomal storage disease with accumulation of undegraded mannosyl-linked oligosaccharides in cells throughout the body, most notably in the CNS. This leads to a broad spectrum of neurological manifestations, including progressive intellectual impairment, disturbed motor functions and cerebellar atrophy. To develop therapeutic outcome measures for enzyme replacement therapy (ERT) that could be used for human patients, a gene knockout model of α-mannosidosis in mice was analyzed for CNS pathology and motor deficits. In the cerebellar molecular layer, α-mannosidosis mice display clusters of activated Bergman glia, infiltration of phagocytic macrophages and accumulation of free cholesterol and gangliosides (GM1), notably in regions lacking Purkinje cells. α-mannosidosis brain lysates also displayed increased expression of Lamp1 and hyperglycosylation of the cholesterol binding protein NPC2. Detailed assessment of motor function revealed age-dependent gait defects in the mice that resemble the disturbed motor function in human patients. Short-term ERT partially reversed the observed cerebellar pathology with fewer activated macrophages and astrocytes but unchanged levels of hyperglycosylated NPC2, gangliosides and cholesterol. The present study demonstrates cerebellar alterations in α-mannosidosis mice that relate to the motor deficits and pathological changes seen in human patients and can be used as therapeutic outcome measures. PMID:21157375

[Neuropsychiatric background of severe drawing disturbances].

PubMed

Molnár, Gábor

2008-01-01

Drawing ability is a primary human skill, which first appeared in the paleolithic art. In spite of this fact, neuropsychology of drawing has been a neglected subject of brain research. In the Crisis Intervention Department at the Budapest Social Center (Hungary), five patients with local brain lesions were identified, who had severe drawing disturbances. This was defined when the form representation in the House-Tree-Person drawing test was was not maintained and was associated with altered figure-perception. Patients were underwent detailed neurological, mental and neuropsychological assessment. Computer tomography of the head was performed at different hospitals in Budapest. House-Tree-Person drawing test was used, which was complemented with copy and visual memory tasks (with Rey-picture), as well as with spontaneous drawing, if it was necessary. Severe drawing disturbances were found in patients with severe right frontal, right temporo-parietal, diffuse right fronto-parieto-temporal, left occipito-temporal lesions and with bilateral basal ganglia lesions with enlarged ventriculi. Impairment of copying figures was sometimes seen without associated impairment of drawing on verbal instructions. Visual memory, visual images in long-term memory, visual analysis, the ability of adequat placement of parts into the whole representation, visuomotor transfer and perhaps the motor drawing programs could be altered separately. Severe drawing disturbance might occur with perfectly maintained writing capabilities. The data indicated that drawing ability requires the intact activity of nearly the whole brain, but it also includes several subfunctions, which could be altered relatively separately.

Relative to typical antipsychotic drugs, aripiprazole is a safer alternative for alleviating behavioral disturbances after experimental brain trauma

PubMed Central

Phelps, Thomas I.; Bondi, Corina O.; Mattiola, Vincent V.; Kline, Anthony E.

2016-01-01

Background Antipsychotic drugs (APDs) are used to manage traumatic brain injury (TBI)-induced behavioral disturbances, such as agitation and aggression. However, APDs exhibiting D2 receptor antagonism impede cognitive recovery after experimental TBI. Hence, empirical evaluation of APDs with different mechanistic actions is warranted. Aripiprazole (ARIP) is a D2 and 5-HT1A receptor agonist; pharmacotherapies with these properties enhance cognition after TBI. Objective To test the hypothesis that ARIP would increase behavioral performance and decrease histopathology after TBI. Methods Adult male rats were subjected to either a controlled cortical impact (CCI) or sham injury and then randomly assigned to ARIP (0.1 or 1.0 mg/kg) or VEH (1.0 mL/kg, saline vehicle) groups. Treatments began 24 hr after surgery and were administered once daily for 19 days. Motor (beam-balance/beam-walk) and cognitive (Morris water maze) performance was assessed on post-operative days 1-5 and 14-19, respectively, followed by quantification of hippocampal CA1/3 neuron survival and cortical lesion volume. Results Beam-balance was significantly improved in the CCI + ARIP (1.0 mg/kg) group vs. CCI + ARIP (0.1 mg/kg) and CCI + VEH [p<0.05]. Spatial learning and memory retention were significantly improved in the CCI + ARIP (0.1 mg/kg) group vs. the CCI + ARIP (1.0 mg/kg) and CCI + VEH groups [p<0.05]. Both doses of ARIP reduced lesion size and CA3 cell loss vs. VEH [p<0.05]. Importantly, neither dose of ARIP impeded functional recovery as previously reported with other APDs. Conclusion These findings support the hypothesis and endorse ARIP as a safer APD for alleviating behavioral disturbances after TBI. PMID:27225976

Neuroanatomy of conversion disorder: towards a network approach.

PubMed

Conejero, Ismael; Thouvenot, Eric; Abbar, Mocrane; Mouchabac, Stéphane; Courtet, Philippe; Olié, Emilie

2018-06-27

The pathophysiology of conversion disorder is not well understood, although studies using functional brain imaging in patients with motor and sensory symptoms are progressively increasing. We conducted a systematic review of the literature with the aim of summarising the available data on the neuroanatomical features of this disorder. We also propose a general model of the neurobiological disturbance in motor conversion disorder. We systematically searched articles in Medline using the Medical Subject Headings terms '(conversion disorder or hysterical motor disorder) and (neuropsychology or cognition) or (functional magnetic resonance imaging or positron emission tomography or neuroimaging) or (genetics or polymorphisms or epigenetics) or (biomarkers or biology)', following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two authors independently reviewed the retrieved records and abstracts, assessed the exhaustiveness of data abstraction, and confirmed the quality rating. Analysis of the available literature data shows that multiple specialised brain networks (self-agency, action monitoring, salience system, and memory suppression) influence action selection and modulate supplementary motor area activation. Some findings suggest that conceptualisation of movement and motor intention is preserved in patients with limb weakness. More studies are needed to fully understand the brain alterations in conversion disorders and pave the way for the development of effective therapeutic strategies.

Amigo adhesion protein regulates development of neural circuits in zebrafish brain.

PubMed

Zhao, Xiang; Kuja-Panula, Juha; Sundvik, Maria; Chen, Yu-Chia; Aho, Vilma; Peltola, Marjaana A; Porkka-Heiskanen, Tarja; Panula, Pertti; Rauvala, Heikki

2014-07-18

The Amigo protein family consists of three transmembrane proteins characterized by six leucine-rich repeat domains and one immunoglobulin-like domain in their extracellular moieties. Previous in vitro studies have suggested a role as homophilic adhesion molecules in brain neurons, but the in vivo functions remain unknown. Here we have cloned all three zebrafish amigos and show that amigo1 is the predominant family member expressed during nervous system development in zebrafish. Knockdown of amigo1 expression using morpholino oligonucleotides impairs the formation of fasciculated tracts in early fiber scaffolds of brain. A similar defect in fiber tract development is caused by mRNA-mediated expression of the Amigo1 ectodomain that inhibits adhesion mediated by the full-length protein. Analysis of differentiated neural circuits reveals defects in the catecholaminergic system. At the behavioral level, the disturbed formation of neural circuitry is reflected in enhanced locomotor activity and in the inability of the larvae to perform normal escape responses. We suggest that Amigo1 is essential for the development of neural circuits of zebrafish, where its mechanism involves homophilic interactions within the developing fiber tracts and regulation of the Kv2.1 potassium channel to form functional neural circuitry that controls locomotion. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Altered Resting State Effective Connectivity of Anterior Insula in Depression.

PubMed

Kandilarova, Sevdalina; Stoyanov, Drozdstoy; Kostianev, Stefan; Specht, Karsten

2018-01-01

Depression has been associated with changes in both functional and effective connectivity of large scale brain networks, including the default mode network, executive network, and salience network. However, studies of effective connectivity by means of spectral dynamic causal modeling (spDCM) are still rare and the interaction between the different resting state networks has not been investigated in detail. Thus, we aimed at exploring differences in effective connectivity among eight right hemisphere brain areas-anterior insula, inferior frontal gyrus, middle frontal gyrus (MFG), frontal eye field, anterior cingulate cortex, superior parietal lobe, amygdala, and hippocampus, between a group of healthy controls ( N  = 20) and medicated depressed patients ( N  = 20). We found that patients not only had significantly reduced strength of the connection from the anterior insula to the MFG (i.e., dorsolateral prefrontal cortex) but also a significant connection between the amygdala and the anterior insula. Moreover, depression severity correlated with connectivity of the hippocampal node. In conclusion, the results from this resting state spDCM study support and enrich previous data on the role of the right anterior insula in the pathophysiology of depression. Furthermore, our findings add to the growing evidence of an association between depression severity and disturbances of the hippocampal function in terms of impaired connectivity with other brain regions.

Altered Resting State Effective Connectivity of Anterior Insula in Depression

PubMed Central

Kandilarova, Sevdalina; Stoyanov, Drozdstoy; Kostianev, Stefan; Specht, Karsten

2018-01-01

Depression has been associated with changes in both functional and effective connectivity of large scale brain networks, including the default mode network, executive network, and salience network. However, studies of effective connectivity by means of spectral dynamic causal modeling (spDCM) are still rare and the interaction between the different resting state networks has not been investigated in detail. Thus, we aimed at exploring differences in effective connectivity among eight right hemisphere brain areas—anterior insula, inferior frontal gyrus, middle frontal gyrus (MFG), frontal eye field, anterior cingulate cortex, superior parietal lobe, amygdala, and hippocampus, between a group of healthy controls (N = 20) and medicated depressed patients (N = 20). We found that patients not only had significantly reduced strength of the connection from the anterior insula to the MFG (i.e., dorsolateral prefrontal cortex) but also a significant connection between the amygdala and the anterior insula. Moreover, depression severity correlated with connectivity of the hippocampal node. In conclusion, the results from this resting state spDCM study support and enrich previous data on the role of the right anterior insula in the pathophysiology of depression. Furthermore, our findings add to the growing evidence of an association between depression severity and disturbances of the hippocampal function in terms of impaired connectivity with other brain regions. PMID:29599728

Fluoro-Jade and TUNEL staining as useful tools to identify ischemic brain damage following moderate extradural compression of sensorimotor cortex.

PubMed

Kundrotiene, Jurgita; Wägner, Anna; Liljequist, Sture

2004-01-01

Cerebral ischemia was produced by moderate compression for 30 min of a specific brain area in the sensorimotor cortex of Sprague-Dawley rats. On day 1, that is 24 h after the transient sensorimotor compression, ischemia-exposed animals displayed a marked focal neurological deficit documented as impaired beam walking performance. This functional disturbance was mainly due to contralateral fore- and hind-limb paresis. As assessed by daily beam walking tests it was shown that there was a spontaneous recovery of motor functions over a period of five to seven days after the ischemic event. Using histopathological analysis (Nissl staining) we have previously reported that the present experimental paradigm does not produce pannecrosis (tissue cavitation) despite the highly reproducible focal neurological deficit. We now show how staining with fluorescent markers for neuronal death, that is Fluoro-Jade and TUNEL, respectively, identifies regional patterns of selective neuronal death. These observations add further support to the working hypothesis that the brain damage caused by cortical compression-induced ischemia consists of scattered, degenerating neurons in specific brain regions. Postsurgical administration of the AMPA receptor specific antagonist, LY326325 (30 mg/kg; i.p., 70 min after compression), not only improved beam walking performance on day 1 to 3, respectively but also significantly reduced the number of Fluoro-Jade stained neurons on day 5. These results suggest that enhanced AMPA/glutamate receptor activity is at least partially responsible for the ischemia-produced brain damage detected by the fluorescent marker Fluoro-Jade.

The effect of aging on brain barriers and the consequences for Alzheimer's disease development.

PubMed

Gorlé, Nina; Van Cauwenberghe, Caroline; Libert, Claude; Vandenbroucke, Roosmarijn E

2016-08-01

Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease.

Effect of meditation on psychological distress and brain functioning: A randomized controlled study.

PubMed

Travis, Fred; Valosek, Laurent; Konrad, Arthur; Link, Janice; Salerno, John; Scheller, Ray; Nidich, Sanford

2018-06-21

Psychological stability and brain integration are important factors related to physical and mental health and organization effectiveness. This study tested whether a mind-body technique, the Transcendental Meditation (TM) program could increase EEG brain integration and positive affect, and decrease psychological distress in government employees. Ninety-six central office administrators and staff at the San Francisco Unified School District were randomly assigned to either immediate start of the TM program or to a wait-list control group. At baseline and four-month posttest, participants completed an online version of the Profile of Mood States questionnaire (POMS). In addition, a subset of this population (N = 79) had their EEG recorded at baseline and at four-month posttest to calculate Brain Integration Scale (BIS) scores. At posttest, TM participants significantly decreased on the POMS Total Mood Disturbance and anxiety, anger, depression, fatigue, and confusion subscales, and significantly increased in the POMS vigor subscale. TM participants in the EEG-subgroup also significantly increased in BIS scores. Compliance with meditation practice was high (93%). Findings indicate the feasibility and effectiveness of implementing the TM program to improve brain integration and positive affect and reduce psychological distress in government administrators and staff. Copyright © 2018. Published by Elsevier Inc.

Cognitive, Affective, and Conative Theory of Mind (ToM) in Children with Traumatic Brain Injury

PubMed Central

Dennis, Maureen; Simic, Nevena; Bigler, Erin D.; Abildskov, Tracy; Agostino, Alba; Taylor, H. Gerry; Rubin, Kenneth; Vannatta, Kathryn; Gerhardt, Cynthia A.; Stancin, Terry; Yeates, Keith Owen

2012-01-01

We studied three forms of dyadic communication involving theory of mind (ToM) in 82 children with traumatic brain injury (TBI) and 61 children with orthopedic injury (OI): Cognitive (concerned with false belief), Affective (concerned with expressing socially deceptive facial expressions), and Conative (concerned with influencing another’s thoughts or feelings). We analyzed the pattern of brain lesions in the TBI group and conducted voxel-based morphometry for all participants in five large-scale functional brain networks, and related lesion and volumetric data to ToM outcomes. Children with TBI exhibited difficulty with Cognitive, Affective, and Conative ToM. The perturbation threshold for Cognitive ToM is higher than that for Affective and Conative ToM, in that Severe TBI disturbs Cognitive ToM but even Mild-Moderate TBI disrupt Affective and Conative ToM. Childhood TBI was associated with damage to all five large-scale brain networks. Lesions in the Mirror Neuron Empathy network predicted lower Conative ToM involving ironic criticism and empathic praise. Conative ToM was significantly and positively related to the package of Default Mode, Central Executive, and Mirror Neuron Empathy networks and, more specifically, to two hubs of the Default Mode network, the posterior cingulate/retrosplenial cortex and the hippocampal formation, including entorhinal cortex and parahippocampal cortex. PMID:23291312

Conditioned reflex activity of rats at later periods after the end of flight aboard the Kosmos-605 biosatellite

NASA Technical Reports Server (NTRS)

Livshits, N. N.; Meyzerov, Y. S.; Apanasenko, Z. I.; Kuznetsova, M. A.

1978-01-01

The aftereffects of spaceflight on the higher nervous activity of rats were studied. A five lane maze with a feeding terminal was used to check such factors as transfer of experience, the habit and speed of reaching the goal in the maze, long term memory, and the dynamics of errors. During the 3rd-7th postflight week, functional disturbances in the rat HNA were manifested in the deterioration of the capacity for the transfer of experience and for locating the feeding compartment in the maze, thus indicating a general decrease of work capacity. The increased number of errors and failures pointed to exhaustion of higher nervous processes and to the weakened functional activity of the brain.

Relationship Between Mood Disturbance and Sleep Quality in Oncology Outpatients at the Initiation of Radiation Therapy

PubMed Central

Van Onselen, Christina; Dunn, Laura B.; Lee, Kathryn; Dodd, Marylin; Koetters, Theresa; West, Claudia; Paul, Steven M.; Aouizerat, Bradley E.; Wara, William; Swift, Patrick; Miaskowski, Christine

2010-01-01

Purpose of the research The purpose of this study was to describe the occurrence of significant mood disturbance and evaluate for differences in sleep quality among four mood groups (i.e., neither anxiety nor depression, only anxiety, only depression, anxiety and depression) prior to the initiation of radiation therapy (RT). Methods and sample Patients (n=179) with breast, prostate, lung, and brain cancer were evaluated prior to the initiation of RT using the Pittsburgh Sleep Quality Index (PSQI), the Center for Epidemiological Studies Depression Scale, and the Spielberger State Anxiety Inventory. Differences in sleep disturbance among the four mood groups were evaluated using analyses of variance. Key results While 38% of the patients reported some type of mood disturbance, 57% of the patients reported sleep disturbance. Patients with clinically significant levels of anxiety and depression reported the highest levels of sleep disturbance. Conclusions Overall, oncology patients with mood disturbances reported more sleep disturbance than those without mood disturbance. Findings suggest that oncology patients need to be assessed for mood and sleep disturbances. PMID:20080444

[Activity of the sympatho-adrenal system in patients with hysterical psychopathy and psychasthenia].

PubMed

Trunova, M M

1978-01-01

The paper is concerned with studies of the sympathoadrenal system activity by the indices of urine excretion of catecholamine and dofa in patients with hysterical and psychasthenic psychopathy. The disorders inherent in each of the groups are demonstrated. The patients with hysterical psychopathy show an exhaustion of all links in the catecholamine metabolism, while the patients with psychasthenical psychopathy an exhaustion of the noradrenaline link. In attempting to explain the mechanisms of disturbed activity in the sympathoadrenal system in both groups the role of the functional state of nonspecific activizing brain systems was taken into consideration.

Neuroimaging Research: from Null-Hypothesis Falsification to Out-Of-Sample Generalization

ERIC Educational Resources Information Center

Bzdok, Danilo; Varoquaux, Gaël; Thirion, Bertrand

2017-01-01

Brain-imaging technology has boosted the quantification of neurobiological phenomena underlying human mental operations and their disturbances. Since its inception, drawing inference on neurophysiological effects hinged on classical statistical methods, especially, the general linear model. The tens of thousands of variables per brain scan were…

Sensory Sensitivities and Discriminations and their Roles in Aviation

DTIC Science & Technology

1991-10-31

asymmetry. Neurology, in press. 5. Zihl JD, Von Cramon D & Mai N (1983) Selective disturbance of movement vision after bilateral brain damage. Brain...1970) Electrophysiological correlate of binocular depth perception in man. Nature 255, 92-4. 1971 16. Regan D & Sperling HG (1971) A method of evoking

Dromosagnosia, or why some people lose their sense of direction while driving.

PubMed

Tseng, Wei-Shih; Tzeng, Nian-Sheng

2013-11-01

We coined a new word, "dromosagnosia", from the Greek words, dromos ("way, road")+agnosia, to describe the loss of direction while driving, an orientation disorder similar to but different from pure topographic disorientation. Historically, human beings have moved more quickly, from using domesticated animals to high speed vehicles, and this may be beyond the brain's ability to react. Without the benefit of an automatic navigation system, automobiles are associated with more problems of dromosagnosia than are fast-moving aircraft or ships. Previous studies have noted that some areas of the brain are associated with spatial orientation, spatial memory, and even emotion, and abnormalities there could exacerbate the loss of sense of direction. We hypothesize that some people are especially disadvantaged from these brain differences and emotional disturbances when driving their cars. Functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) studies combined with a virtual reality driving simulation might be used to find the areas of the brain related to dromosagnosia. Future applications: some people with dromosagnosia might benefit from special remedial training and a driving safety support system to avoid potential problems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Glutamate and Glutamine: A Review of In Vivo MRS in the Human Brain

PubMed Central

Ramadan, Saadallah; Lin, Alexander; Stanwell, Peter

2013-01-01

Our understanding of the roles that the amino acids glutamate (Glu) and glutamine (Gln) play in the mammalian central nervous system has increased rapidly in recent times. Many conditions are known to exhibit a disturbance in Glu-Gln equilibrium and the exact relationship between these changed conditions and these amino acids are not fully understood. This has led to increased interest in Glu/Gln quantitation in the human brain in an array of conditions (e.g. mental illness, tumor, neuro-degeneration) as well as in normal brain function. Accordingly, this review has been undertaken to describe the increasing number of in vivo techniques available to study Glu and Gln separately, or pooled as ‘Glx’. The present range of magnetic resonance spectroscopy (MRS) methods used to assess Glu and Gln, vary in approach, complexity and outcome, thus the focus of this review is on a description of MRS acquisition approaches, and an indication of relative utility of each technique rather than brain pathologies associated to Glu and/or Gln perturbation. Consequently, this review focuses particularly on (1) one-dimensional (1D) 1H MRS, (2) two-dimensional (2D) 1H MRS, and (3) 1D 13C MRS techniques. PMID:24123328

Functional and structural abnormalities associated with empathy in patients with schizophrenia: An fMRI and VBM study

PubMed Central

Singh, Sadhana; Modi, Shilpi; Goyal, Satnam; Kaur, Prabhjot; Singh, Namita; Bhatia, Triptish; Deshpande, Smita N; Khushu, Subash

2016-01-01

Empathy deficit is a core feature of schizophrenia which may lead to social dysfunction. The present study was carried out to investigate functional and structural abnormalities associated with empathy in patients with schizophrenia using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). A sample of 14 schizophrenia patients and 14 healthy control subjects matched for age, sex and education were examined with structural high-resolution T1-weighted MRI; fMRI images were obtained during empathy task in the same session. The analysis was carried out using SPM8 software. On behavioural assessment, schizophrenic patients (83.00±29.04) showed less scores for sadness compared to healthy controls (128.70±22.26) (p<0.001). fMRI results also showed reduced clusters of activation in the bilateral fusiform gyrus, left lingual gyrus, left middle and inferior occipital gyrus in schizophrenic subjects as compared to controls during empathy task. In the same brain areas, VBM results also showed reduced grey and white matter volumes. The present study provides an evidence for an association between structural alterations and disturbed functional brain activation during empathy task in persons affected with schizophrenia. These findings suggest a biological basis for social cognition deficits in schizophrenics. PMID:25963262

Functional and structural abnormalities associated with empathy in patients with schizophrenia: An fMRI and VBM study.

PubMed

Singh, Sadhana; Modi, Shilpi; Goyal, Satnam; Kaur, Prabhjot; Singh, Namita; Bhatia, Triptish; Deshpande, Smita N; Khushu, Subash

2015-06-01

Empathy deficit is a core feature of schizophrenia which may lead to social dysfunction. The present study was carried out to investigate functional and structural abnormalities associated with empathy in patients with schizophrenia using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). A sample of 14 schizophrenia patients and 14 healthy control subjects matched for age, sex and education were examined with structural highresolution T1-weighted MRI; fMRI images were obtained during empathy task in the same session. The analysis was carried out using SPM8 software. On behavioural assessment, schizophrenic patients (83.00+-29.04) showed less scores for sadness compared to healthy controls (128.70+-22.26) (p less than 0.001). fMRI results also showed reduced clusters of activation in the bilateral fusiform gyrus, left lingual gyrus, left middle and inferior occipital gyrus in schizophrenic subjects as compared to controls during empathy task. In the same brain areas, VBM results also showed reduced grey and white matter volumes. The present study provides an evidence for an association between structural alterations and disturbed functional brain activation during empathy task in persons affected with schizophrenia. These findings suggest a biological basis for social cognition deficits in schizophrenics.

Resting-State Functional Connectivity in Patients with Long-Term Remission of Cushing's Disease.

PubMed

van der Werff, Steven J A; Pannekoek, J Nienke; Andela, Cornelie D; Meijer, Onno C; van Buchem, Mark A; Rombouts, Serge A R B; van der Mast, Roos C; Biermasz, Nienke R; Pereira, Alberto M; van der Wee, Nic J A

2015-07-01

Glucocorticoid disturbance can be a cause of psychiatric symptoms. Cushing's disease represents a unique model for examining the effects of prolonged exposure to high levels of endogenous cortisol on the human brain as well as for examining the relation between these effects and psychiatric symptomatology. This study aimed to investigate resting-state functional connectivity (RSFC) of the limbic network, the default mode network (DMN), and the executive control network in patients with long-term remission of Cushing's disease. RSFC of these three networks of interest was compared between patients in remission of Cushing's disease (n=24; 4 male, mean age=44.96 years) and matched healthy controls (n=24; 4 male, mean age=46.5 years), using probabilistic independent component analysis to extract the networks and a dual regression method to compare both groups. Psychological and cognitive functioning was assessed with validated questionnaires and interviews. In comparison with controls, patients with remission of Cushing's disease showed an increased RSFC between the limbic network and the subgenual subregion of the anterior cingulate cortex (ACC) as well as an increased RSFC of the DMN in the left lateral occipital cortex. However, these findings were not associated with psychiatric symptoms in the patient group. Our data indicate that previous exposure to hypercortisolism is related to persisting changes in brain function.

Long-term functional outcome of patients with cerebellar pilocytic astrocytoma surgically treated in childhood.

PubMed

Ait Khelifa-Gallois, N; Laroussinie, F; Puget, S; Sainte-Rose, C; Dellatolas, G

2015-01-01

Abstract Purpose: A number of studies report neurological and cognitive deficits and behavioural disorders in children after surgical treatment for a benign cerebellar tumour. The present study explores functional outcome in adolescents and adults treated for a low-grade cerebellar astrocytoma in childhood. Participants were 18 adolescents and 46 adults treated for low-grade astrocytoma in childhood. Academic achievement, professional status and neurological, cognitive and behavioural disturbances were collected using self-completed and parental questionnaires for adolescents and phone interview for adults. For the adolescent group, a control group filled in the same questionnaires. Mean time lapse from surgery was 7.8 years for adolescents and 12.9 years for adults. Five adults (11%) had major sequelae related to post-operative complications, post-operative mutism and/or brain stem involvement. All the other participants presented close-to-normal academic achievement and normal autonomy, despite a high rate of reported cognitive difficulties and difficulties related to mild neurological sequelae (fine motor skills, balance). The long-term functional outcome of low-grade cerebellar astrocytoma is generally favourable, in the absence of post-operative complications and brain stem involvement. No major impact of neurological deficits, cognitive problems and emotional disorders on academic achievement and independent functioning was observed.

GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia.

PubMed

Gonzalez-Burgos, Guillermo; Fish, Kenneth N; Lewis, David A

2011-01-01

Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.

PubMed

Nakagawa, Yutaka; Chiba, Kenji

2016-09-01

Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

The Significance of Brain Transcranial Sonography in Burning Mouth Syndrome: a Pilot Study

PubMed Central

Zavoreo, Iris; Vučićević, Vanja; Zadravec, Dijana; Bašić, Vanja; Kes; Ciliga, Dubravka; Gabrić, Dragana

2017-01-01

Objective Burning mouth syndrome (BMS) is a chronic disorder which is affecting mostly postmenopausal women and is characterized by burning symptoms in the oral cavity on the clinically healthy oral mucosa. Also, the results of previous studies suggested a possible role of peripheral and/or central neurological disturbances in these patients. The aim of this study was to analyze patients with burning mouth syndrome using transcranial sonography. Methods By use of transcranial sonography of the brain parenchyma, substantia nigra, midbrain raphe and brain nucleus were evaluated in 20 patients with BMS (64.7±12.3 years) and 20 controls with chronic pain in the lumbosacral region (61.5±15). Statistical analysis was performed by use of Student t test with significance set at p<0.05. Results The results of this study have shown hypoechogenicity of the substantia nigra and midbrain raphe as well as hyperechogenicity of the brain nucleus in BMS patients (p<0,05) as compared to controls. Conclusions Altered transcranial sonography findings of the brain parenchyma, midbrain raphe and brain nucleus in patients with burning mouth syndrome might reflect central disturbances within this syndrome. Key words Burning Mouth Syndrome; Transcranial Sonography; substantia nigra; Midbrain Raphe Nuclei; Red Nucleus PMID:28740270

Egocentric spatial learning in schizophrenia investigated with functional magnetic resonance imaging☆

PubMed Central

Siemerkus, Jakob; Irle, Eva; Schmidt-Samoa, Carsten; Dechent, Peter; Weniger, Godehard

2012-01-01

Psychotic symptoms in schizophrenia are related to disturbed self-recognition and to disturbed experience of agency. Possibly, these impairments contribute to first-person large-scale egocentric learning deficits. Sixteen inpatients with schizophrenia and 16 matched healthy comparison subjects underwent functional magnetic resonance imaging (fMRI) while finding their way in a virtual maze. The virtual maze presented a first-person view, lacked any topographical landmarks and afforded egocentric navigation strategies. The participants with schizophrenia showed impaired performance in the virtual maze when compared with controls, and showed a similar but weaker pattern of activity changes during egocentric learning when compared with controls. Especially the activity of task-relevant brain regions (precuneus and posterior cingulate and retrosplenial cortex) differed from that of controls across all trials of the task. Activity increase within the right-sided precuneus was related to worse virtual maze performance and to stronger positive symptoms in participants with schizophrenia. We suggest that psychotic symptoms in schizophrenia are related to aberrant neural activity within the precuneus. Possibly, first-person large-scale egocentric navigation and learning designs may be a feasible tool for the assessment and treatment of cognitive deficits related to self-recognition in patients with schizophrenia. PMID:24179748

Gray matter changes in right superior temporal gyrus in criminal psychopaths. Evidence from voxel-based morphometry.

PubMed

Müller, Jürgen L; Gänssbauer, Susanne; Sommer, Monika; Döhnel, Katrin; Weber, Tatjana; Schmidt-Wilcke, Tobias; Hajak, Göran

2008-08-30

"Psychopathy" according to the PCL-R describes a specific subgroup of antisocial personality disorder with a high risk for criminal relapses. Lesion and imaging studies point towards frontal or temporal brain regions connected with disturbed social behavior, antisocial personality disorder (APD) and psychopathy. Morphologically, some studies described a reduced prefrontal brain volume, whereas others reported on temporal lobe atrophy. To further investigate whether participants with psychopathy according to the Psychopathy Checklist-Revised Version (PCL-R) show abnormalities in brain structure, we used voxel-based morphometry (VBM) to investigate region-specific changes in gray matter in 17 forensic male inpatients with high PCL-R scores (PCL-R>28) and 17 male control subjects with low PCL-R scores (PCL<10). We found significant gray matter reductions in frontal and temporal brain regions in psychopaths compared with controls. In particular, we found a highly significant volume loss in the right superior temporal gyrus. This is the first study to show that psychopathy is associated with a decrease in gray matter in both frontal and temporal brain regions, in particular in the right superior temporal gyrus, supporting the hypothesis that a disturbed frontotemporal network is critically involved in the pathogenesis of psychopathy.

Neuroplastic Changes Induced by Cognitive Rehabilitation in Traumatic Brain Injury: A Review.

PubMed

Galetto, Valentina; Sacco, Katiuscia

2017-09-01

Cognitive deficits are among the most disabling consequences of traumatic brain injury (TBI), leading to long-term outcomes and interfering with the individual's recovery. One of the most effective ways to reduce the impact of cognitive disturbance in everyday life is cognitive rehabilitation, which is based on the principles of brain neuroplasticity and restoration. Although there are many studies in the literature focusing on the effectiveness of cognitive interventions in reducing cognitive deficits following TBI, only a few of them focus on neural modifications induced by cognitive treatment. The use of neuroimaging or neurophysiological measures to evaluate brain changes induced by cognitive rehabilitation may have relevant clinical implications, since they could add individualized elements to cognitive assessment. Nevertheless, there are no review studies in the literature investigating neuroplastic changes induced by cognitive training in TBI individuals. Due to lack of data, the goal of this article is to review what is currently known on the cerebral modifications following rehabilitation programs in chronic TBI. Studies investigating both the functional and structural neural modifications induced by cognitive training in TBI subjects were identified from the results of database searches. Forty-five published articles were initially selected. Of these, 34 were excluded because they did not meet the inclusion criteria. Eleven studies were found that focused solely on the functional and neurophysiological changes induced by cognitive rehabilitation. Outcomes showed that cerebral activation may be significantly modified by cognitive rehabilitation, in spite of the severity of the injury.

Neurotoxic lupus autoantibodies alter brain function through two distinct mechanisms

PubMed Central

Faust, Thomas W.; Chang, Eric H.; Kowal, Czeslawa; Berlin, RoseAnn; Gazaryan, Irina G.; Bertini, Eva; Zhang, Jie; Sanchez-Guerrero, Jorge; Fragoso-Loyo, Hilda E.; Volpe, Bruce T.; Diamond, Betty; Huerta, Patricio T.

2010-01-01

Damaging interactions between antibodies and brain antigenic targets may be responsible for an expanding range of neurological disorders. In the case of systemic lupus erythematosus (SLE), patients generate autoantibodies (AAbs) that frequently bind dsDNA. Although some symptoms of SLE may arise from direct reactivity to dsDNA, much of the AAb-mediated damage originates from cross-reactivity with other antigens. We have studied lupus AAbs that bind dsDNA and cross-react with the NR2A and NR2B subunits of the NMDA receptor (NMDAR). In adult mouse models, when the blood–brain barrier is compromised, these NMDAR-reactive AAbs access the brain and elicit neuronal death with ensuing cognitive dysfunction and emotional disturbance. The cellular mechanisms that underlie these deleterious effects remain incompletely understood. Here, we show that, at low concentration, the NMDAR-reactive AAbs are positive modulators of receptor function that increase the size of NMDAR-mediated excitatory postsynaptic potentials, whereas at high concentration, the AAbs promote excitotoxicity through enhanced mitochondrial permeability transition. Other synaptic receptors are completely unaffected by the AAbs. NMDAR activation is required for producing both the synaptic and the mitochondrial effects. Our study thus reveals the mechanisms by which NMDAR-reactive AAbs trigger graded cellular alterations, which are likely to be responsible for the transient and permanent neuropsychiatric symptoms observed in patients with SLE. Our study also provides a model in which local AAb concentration determines the exact nature of the cellular response. PMID:20921396

Post-operative cognitive dysfunction after knee arthroplasty: a diagnostic dilemma

PubMed Central

Yap, Kiryu K.; Joyner, Peter

2014-01-01

Post-operative cognitive dysfunction (POCD) is common in the elderly, and significantly impacts their recovery. We present an unusual diagnostic challenge where a 65-year-old male presented 4-week post-total knee arthroplasty with acute cognitive dysfunction lasting 19 days. Curiously, there were no findings uncovering a specific cause, but during investigation underlying predisposing factors such as depression, mild memory deficits and generalized brain volume loss were identified. The impression after psychogeriatric review was that of an organic brain syndrome with overlay of depression, with a complex presentation as POCD. After escalation of behavioural disturbance, he was commenced on anti-psychotic/depressant, with immediate response. We emphasize the importance of pre-operative evaluation of cognitive function and risk factors in all geriatric patients undergoing elective surgery, and the need for further characterization of POCD, as well as experimental research elucidating the underlying mechanisms to better identify and treat this important post-surgical phenomenon. PMID:25988029

Management of stroke as described by Ibn Sina (Avicenna) in the Canon of Medicine.

PubMed

Zargaran, Arman; Zarshenas, Mohammad M; Karimi, Aliasghar; Yarmohammadi, Hassan; Borhani-Haghighi, Afshin

2013-11-15

Stroke or cerebrovascular accident (CVA) is caused by a disturbance of the blood supply to the brain and an accruing loss of brain function. The first recorded observations were in 2455 BC and it has been studied intensely by ancient physicians throughout history. In the early medieval period, Ibn Sina (980-1025 AD) called stroke sekteh and described it extensively. Some of Ibn Sina's definitions and his etiology of stroke are based on humoral theories and cannot be compared with medical current concepts, but most of his descriptions concur with current definitions. This review examines the definition and etiology, clinical manifestations, prognosis, differential diagnosis, and interventions for stroke based on Ibn Sina's epic work, Canon of Medicine. The pharmacological effects of medicinal herbs suggested by Ibn Sina for stroke are examined in light of current knowledge. © 2013.

Crosstalk between metabolic and neuropsychiatric disorders

PubMed Central

Cha, Danielle S.

2012-01-01

Evidence supporting the concurrence of metabolic disturbances (e.g. insulin resistance, diabetes and obesity) and neuropsychiatric disorders has been demonstrated in both human and animal studies, suggesting the possibility that they have shared pathophysiological mechanisms. During the past decade, our understanding for the role of insulin in both normal and abnormal central nervous system (CNS) processes has become increasingly refined. Evidence indicates that insulin is a pleiotropic peptide, critical to neurotrophism, neuroplasticity, and neuromodulation. Moreover, the role of insulin underscores its importance in the development of several neuropsychiatric disorders, including, but not limited to, mechanisms involved in the pathogenesis and progression towards diabetes, obesity, and neurodegenerative disorders, such as Alzheimer's disease. This review focuses on the insulin-mediated effects on normal and abnormal brain function and discusses why targeting insulin-related pathways in the brain may emerge as a new approach for refining treatment of neurological and psychiatric disorders. PMID:22802875

Crosstalk between metabolic and neuropsychiatric disorders.

PubMed

Kaidanovich-Beilin, Oksana; Cha, Danielle S; McIntyre, Roger S

2012-01-01

Evidence supporting the concurrence of metabolic disturbances (e.g. insulin resistance, diabetes and obesity) and neuropsychiatric disorders has been demonstrated in both human and animal studies, suggesting the possibility that they have shared pathophysiological mechanisms. During the past decade, our understanding for the role of insulin in both normal and abnormal central nervous system (CNS) processes has become increasingly refined. Evidence indicates that insulin is a pleiotropic peptide, critical to neurotrophism, neuroplasticity, and neuromodulation. Moreover, the role of insulin underscores its importance in the development of several neuropsychiatric disorders, including, but not limited to, mechanisms involved in the pathogenesis and progression towards diabetes, obesity, and neurodegenerative disorders, such as Alzheimer's disease. This review focuses on the insulin-mediated effects on normal and abnormal brain function and discusses why targeting insulin-related pathways in the brain may emerge as a new approach for refining treatment of neurological and psychiatric disorders.

The role of recurrent disturbances for ecosystem multifunctionality.

PubMed

Villnäs, Anna; Norkko, Joanna; Hietanen, Susanna; Josefson, Alf B; Lukkari, Kaarina; Norkko, Alf

2013-10-01

Ecosystem functioning is threatened by an increasing number of anthropogenic stressors, creating a legacy of disturbance that undermines ecosystem resilience. However, few empirical studies have assessed to what extent an ecosystem can tolerate repeated disturbances and sustain its multiple functions. By inducing increasingly recurring hypoxic disturbances to a sedimentary ecosystem, we show that the majority of individual ecosystem functions experience gradual degradation patterns in response to repetitive pulse disturbances. The degradation in overall ecosystem functioning was, however, evident at an earlier stage than for single ecosystem functions and was induced after a short pulse of hypoxia (i.e., three days), which likely reduced ecosystem resistance to further hypoxic perturbations. The increasing number of repeated pulse disturbances gradually moved the system closer to a press response. In addition to the disturbance regime, the changes in benthic trait composition as well as habitat heterogeneity were important for explaining the variability in overall ecosystem functioning. Our results suggest that disturbance-induced responses across multiple ecosystem functions can serve as a warning signal for losses of the adaptive capacity of an ecosystem, and might at an early stage provide information to managers and policy makers when remediation efforts should be initiated.

Behavioral, Brain Imaging and Genomic Measures to Predict Functional Outcomes Post-Bed Rest and Space Flight

NASA Technical Reports Server (NTRS)

Mulavara, A. P.; Peters, B.; De Dios, Y. E.; Gadd, N. E.; Caldwell, E. E.; Batson, C. D.; Goel, R.; Oddsson, L.; Kreutzberg, G.; Zanello, S.;

Disturbance by an endemic rodent in an arid shrubland is a habitat filter: effects on plant invasion and taxonomical, functional and phylogenetic community structure

PubMed Central

Escobedo, Víctor M.; Rios, Rodrigo S.; Salgado-Luarte, Cristian; Stotz, Gisela C.

2017-01-01

Abstract Background and Aims Disturbance often drives plant invasion and may modify community assembly. However, little is known about how these modifications of community patterns occur in terms of taxonomic, functional and phylogenetic structure. This study evaluated in an arid shrubland the influence of disturbance by an endemic rodent on community functional divergence and phylogenetic structure as well as on plant invasion. It was expected that disturbance would operate as a habitat filter favouring exotic species with short life cycles. Methods Sixteen plots were sampled along a disturbance gradient caused by the endemic fossorial rodent Spalacopus cyanus, measuring community parameters and estimating functional divergence for life history traits (functional dispersion index) and the relative contribution to functional divergence of exotic and native species. The phylogenetic signal (Pagel’s lambda) and phylogenetic community structure (mean phylogenetic distance and mean nearest taxon phylogenetic distance) were also estimated. The use of a continuous approach to the disturbance gradient allowed the identification of non-linear relationships between disturbance and community parameters. Key Results The relationship between disturbance and both species richness and abundance was positive for exotic species and negative for native species. Disturbance modified community composition, and exotic species were associated with more disturbed sites. Disturbance increased trait convergence, which resulted in phylogenetic clustering because traits showed a significant phylogenetic signal. The relative contribution of exotic species to functional divergence increased, while that of natives decreased, with disturbance. Exotic and native species were not phylogenetically distinct. Conclusions Disturbance by rodents in this arid shrubland constitutes a habitat filter over phylogeny-dependent life history traits, leading to phylogenetic clustering, and drives invasion by favouring species with short life cycles. Results can be explained by high phenotypic and phylogenetic resemblance between exotic and native species. The use of continuous gradients when studying the effects of disturbance on community assembly is advocated. PMID:28087661

Presynaptic Mechanisms of l-DOPA-Induced Dyskinesia: The Findings, the Debate, and the Therapeutic Implications.

PubMed

Cenci, M Angela

2014-01-01

The dopamine (DA) precursor l-DOPA has been the most effective treatment for Parkinson's disease (PD) for over 40 years. However, the response to this treatment changes with disease progression, and most patients develop dyskinesias (abnormal involuntary movements) and motor fluctuations within a few years of l-DOPA therapy. There is wide consensus that these motor complications depend on both pre- and post-synaptic disturbances of nigrostriatal DA transmission. Several presynaptic mechanisms converge to generate large DA swings in the brain concomitant with the peaks-and-troughs of plasma l-DOPA levels, while post-synaptic changes engender abnormal functional responses in dopaminoceptive neurons. While this general picture is well-accepted, the relative contribution of different factors remains a matter of debate. A particularly animated debate has been growing around putative players on the presynaptic side of the cascade. To what extent do presynaptic disturbances in DA transmission depend on deficiency/dysfunction of the DA transporter, aberrant release of DA from serotonin neurons, or gliovascular mechanisms? And does noradrenaline (which is synthetized from DA) play a role? This review article will summarize key findings, controversies, and pending questions regarding the presynaptic mechanisms of l-DOPA-induced dyskinesia. Intriguingly, the debate around these mechanisms has spurred research into previously unexplored facets of brain plasticity that have far-reaching implications to the treatment of neuropsychiatric disease.

Reversal of normal cerebral sexual dimorphism in schizophrenia: evidence and speculations.

PubMed

Mendrek, Adrianna

2007-01-01

Sex differences in epidemiology, clinical course and symptomatology of schizophrenia have been widely documented, but still relatively little is known about the brain sexual dimorphism in this psychiatric disorder. While some neuroanatomical and neuropsychological studies have reported existence of differences between male and female patients in a direction of normal sexual dimorphism, others did not find any effect. A few recent reports point to a peculiar disturbance of normal sexual dimorphism in brain regions implicated in the processing of emotions, including amygdala, orbitofrontal cortex and anterior cingulate. Prompted by these findings we compared cerebral activations between the sexes during performance of two emotion processing tasks and found overall much more extensive and intense cerebral activations in men than in women with schizophrenia. Moreover, the pattern of obtained sex differences in cerebral activation in patients differed significantly from what has been observed in the general population. Based on these preliminary structural and functional neuroimaging data, as well as some clinical reports, it is hypothesized in the present paper that schizophrenia is characterized by a reversed (or at least seriously disturbed) cerebral sexual dimorphism. It is further argued that this phenomenon stems from masculinization and/or un-feminization of females and feminizations and/or un-masculinization of males by sex steroid hormones, such as estrogen and testosterone, during both organizational and activational stages of neurodevelopment.

Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury.

PubMed

Reifschneider, Kent; Auble, Bethany A; Rose, Susan R

2015-07-31

Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children's quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6-12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life.

Update of Endocrine Dysfunction following Pediatric Traumatic Brain Injury

PubMed Central

Reifschneider, Kent; Auble, Bethany A.; Rose, Susan R.

2015-01-01

Traumatic brain injuries (TBI) are common occurrences in childhood, often resulting in long term, life altering consequences. Research into endocrine sequelae following injury has gained attention; however, there are few studies in children. This paper reviews the pathophysiology and current literature documenting risk for endocrine dysfunction in children suffering from TBI. Primary injury following TBI often results in disruption of the hypothalamic-pituitary-adrenal axis and antidiuretic hormone production and release, with implications for both acute management and survival. Secondary injuries, occurring hours to weeks after TBI, result in both temporary and permanent alterations in pituitary function. At five years after moderate to severe TBI, nearly 30% of children suffer from hypopituitarism. Growth hormone deficiency and disturbances in puberty are the most common; however, any part of the hypothalamic-pituitary axis can be affected. In addition, endocrine abnormalities can improve or worsen with time, having a significant impact on children’s quality of life both acutely and chronically. Since primary and secondary injuries from TBI commonly result in transient or permanent hypopituitarism, we conclude that survivors should undergo serial screening for possible endocrine disturbances. High indices of suspicion for life threatening endocrine deficiencies should be maintained during acute care. Additionally, survivors of TBI should undergo endocrine surveillance by 6–12 months after injury, and then yearly, to ensure early detection of deficiencies in hormonal production that can substantially influence growth, puberty and quality of life. PMID:26287247

Sex and Stress Hormone Influences on the Expression and Activity of Brain-Derived Neurotrophic Factor

PubMed Central

Carbone, David L.; Handa, Robert J.

2012-01-01

The neurotrophin, brain-derived neurotrophic factor (BDNF), is recognized as a key component in the regulation of central nervous system ontogeny, homeostasis and adult neuroplasticity. The importance of BDNF in central nervous system development and function is well documented by numerous reports from animal studies linking abnormal BDNF signaling to metabolic disturbances and anxiety or depressive-like behavior. Despite the diverse roles for BDNF in nearly all aspects of central nervous system physiology, the regulation of BDNF expression, as well as our understanding of the signaling mechanisms associated with this neurotrophin, remains incomplete. However, links between sex hormones such as estradiol and testosterone, as well as endogenous and synthetic glucocorticoids, have emerged as important mediators of BDNF expression and function. Examples of such regulation include brain region-specific induction of Bdnf mRNA in response to estradiol. Additional studies have also documented regulation of the expression of the high-affinity BDNF receptor TrkB by estradiol, thus implicating sex steroids not only in the regulation of BDNF expression, but on mechanisms of signaling associated with it. In addition to gonadal steroids, further evidence also suggests functional interaction between BDNF and glucocorticoids, such as in the regulation of corticotrophin-releasing hormone and other important neuropeptides. In this review, we provide an overview of the roles played by selected sex or stress hormones in the regulation of BDNF expression and signaling in the central nervous system PMID:23211562

Physical exercise protects against Alzheimer's disease in 3xTg-AD mice.

PubMed

García-Mesa, Yoelvis; López-Ramos, Juan Carlos; Giménez-Llort, Lydia; Revilla, Susana; Guerra, Rafael; Gruart, Agnès; Laferla, Frank M; Cristòfol, Rosa; Delgado-García, José M; Sanfeliu, Coral

2011-01-01

Physical exercise is considered to exert a positive neurophysiological effect that helps to maintain normal brain activity in the elderly. Expectations that it could help to fight Alzheimer's disease (AD) were recently raised. This study analyzed the effects of different patterns of physical exercise on the 3xTg-AD mouse. Male and female 3xTg-AD mice at an early pathological stage (4-month-old) have had free access to a running wheel for 1 month, whereas mice at a moderate pathological stage(7-month-old) have had access either during 1 or 6 months. The non-transgenic mouse strain was used as a control. Parallel animal groups were housed in conventional conditions. Cognitive loss and behavioral and psychological symptoms of dementia (BPSD)-like behaviors were present in the 3xTg-AD mice along with alteration in synaptic function and ong-term potentiation impairment in vivo. Brain tissue showed AD-pathology and oxidative-related changes. Disturbances were more severe at the older age tested. Oxidative stress was higher in males but other changes were similar or higher in females. Exercise treatment ameliorated cognitive deterioration and BPSD-like behaviors such as anxiety and the startle response. Synaptic changes were partially protected by exercise. Oxidative stress was reduced. The best neuroprotection was generally obtained after 6 months of exercise in 7-month-old 3xTg-AD mice. Improved sensorimotor function and brain tissue antioxidant defence were induced in both 3xTg-AD and NonTg mice. Therefore, the benefits of aerobic physical exercise on synapse, redox homeostasis, and general brain function demonstrated in the 3xTg-AD mouse further support the value of this healthy life-style against neurodegeneration.

Identifying functional groups for response to disturbance in an abandoned pasture

NASA Astrophysics Data System (ADS)

Lavorel, Sandra; Touzard, Blaise; Lebreton, Jean-Dominique; Clément, Bernard

1998-06-01

In an abandoned pasture in Brittany, we compared artificial small-scale disturbances to natural disturbances by wild boar and undisturbed vegetation. We developed a multivariate statistical approach which analyses how species biological attributes explain the response of community composition to disturbances. This technique, which reconciles the inductive and deductive approaches for functional classifications, identifies groups of species with similar responses to disturbance and characterizes their biological profiles. After 5 months of recolonization, artificial disturbances had a greater species richness than undisturbed vegetation as a result of recruitment of new species without the exclusion of pre-existing matrix species. Species morphology, described by canopy structure, canopy height and lateral spread, explained a large part (16 %) of community response to disturbance. Regeneration strategies, described by life history, seed mass, dispersal agent, dormancy and the existence of vegetative multiplication, explained a smaller part of community response to disturbance (8 %). Artificial disturbances were characterized by therophyte and compact rosettes with moderately dormant seeds, including a number of Asteraceae and other early successional species. Natural disturbances were colonized by leafy guerrilla species without seed dormancy. Few species were tightly related to undisturbed vegetation and were essentially grasses with a phalanx rosette morphology. The functional classification obtained is consistent with the classification of the community into fugitives, regenerators and persistors. These groups are structured according to Grubb's model for temperate grasslands, with regenerators and persistors in the matrix and fugitives taking advantage of gaps open by small-scale disturbances. The conjunction of functional diversity and species diversity within functional groups is the key to resilience to disturbance, an important ecosystem function.

Interventions for Students with Traumatic Brain Injury: Managing Behavioral Disturbances.

ERIC Educational Resources Information Center

Kehle, Thomas J.; And Others

1996-01-01

This article discusses behavioral sequelae common in children and adolescents following a traumatic brain injury (TBI) and the design of intervention strategies. Emphasis is on the unique needs of these students and the cognitive sequelae of TBI (such as impaired attention, reasoning, learning, and memory) that can cause further behavioral…

The Cognitive Basis for Sentence Planning Difficulties in Discourse after Traumatic Brain Injury

ERIC Educational Resources Information Center

Peach, Richard K.

2013-01-01

Purpose: Analyses of language production of individuals with traumatic brain injury (TBI) place increasing emphasis on microlinguistic (i.e., within-sentence) patterns. It is unknown whether the observed problems involve implementation of well-formed sentence frames or represent a fundamental linguistic disturbance in computing sentence structure.…

Alteration in mitochondrial function and glutamate metabolism affected by 2-chloroethanol in primary cultured astrocytes.

PubMed

Sun, Qi; Liao, Yingjun; Wang, Tong; Wang, Gaoyang; Zhao, Fenghong; Jin, Yaping

2016-12-01

The aim of this study was to explore the mechanisms that contribute to 1,2-dichloroethane (1,2-DCE) induced brain edema by focusing on alteration of mitochondrial function and glutamate metabolism in primary cultured astrocytes induced by 2-chloroethanol (2-CE), a metabolite of 1,2-DCE in vivo. The cells were exposed to different levels of 2-CE in the media for 24h. Mitochondrial function was evaluated by its membrane potential and intracellular contents of ATP, lactic acid and reactive oxygen species (ROS). Glutamate metabolism was indicated by expression of glutamine synthase (GS), glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) at both protein and gene levels. Compared to the control group, exposure to 2-CE could cause a dose dependent damage in astrocytes, indicated by decreased cell viability and morphological changes, and supported by decreased levels of nonprotein sulfhydryl (NPSH) and inhibited activities of Na + /K + -ATPase and Ca 2+ -ATPase in the cells. The present study also revealed both mitochondrial function and glutamate metabolism in astrocytes were significantly disturbed by 2-CE. Of which, mitochondrial function was much vulnerable to the effects of 2-CE. In conclusion, our findings suggested that mitochondrial dysfunction and glutamate metabolism disorder could contribute to 2-CE-induced cytotoxicity in astrocytes, which might be related to 1,2-DCE-induced brain edema. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pusher syndrome--a frequent but little-known disturbance of body orientation perception.

PubMed

Karnath, Hans-Otto

2007-04-01

Disturbances of body orientation perception after brain lesions may specifically relate to only one dimension of space. Stroke patients with "pusher syndrome" suffer from a severe misperception of their body's orientation in the coronal (roll) plane. They experience their body as oriented 'upright' when it is in fact markedly tilted to one side. The patients use the unaffected arm or leg to actively push away from the un-paralyzed side and resist any attempt to passively correct their tilted body posture. Although pusher patients are unable to correctly determine when their own body is oriented in an upright, vertical position, they seem to have no significant difficulty in determining the orientation of the surrounding visual world in relation to their own body. Pusher syndrome is a distinctive clinical disorder occurring characteristically after unilateral left or right brain lesions in the posterior thalamus and -less frequently- in the insula and postcentral gyrus. These structures thus seem to constitute crucial neural substrates controlling human (upright) body orientation in the coronal (roll) plane. A further disturbance of body orientation that predominantly affects a single dimension of space, namely the transverse (yaw) plane, is observed in stroke patients with spatial neglect. Apparently, our brain has evolved separate neural subsystems for perceiving and controlling body orientation in different dimensions of space.

High-frequency cortical subdural stimulation enhanced plasticity in surgery of a tumor in Broca's area.

PubMed

Barcia, Juan A; Sanz, Ana; Balugo, Paloma; Alonso-Lera, Pedro; Brin, Juan Raúl; Yus, Miguel; Gonzalez-Hidalgo, Mercedes; Acedo, Victoria M; Oliviero, Antonio

2012-03-28

Functional areas located near or within brain gliomas prevent the complete resection of these tumors. It has recently been described that slow tumor invasion promotes neural reorganization, and even topographic plasticity, allowing a staged resection of those tumors. Thus, our aim was to promote plasticity by mimicking the tumor's capability to displace brain function. This proceeded through the production of a 'virtual lesion' in eloquent areas within a tumor using continuous high-frequency cortical electrical stimulation (cHFCS). An anaplastic astrocytoma located in Broca's area progressed in a patient whose lateralization of language to the side of the lesion was demonstrated with functional MRI. After partial tumor resection using awake cortical monitoring, we implanted a subdural grid over the eloquent cortex located within residual tumor. We then applied cHFCS for 25 days, using a frequency of 130 Hz and a pulse width of 1 ms. Stimulus intensity was set to the threshold wherein mild speech disturbance was evident without any other neurological effects. This treatment successfully achieved the displacement of speech functions, and a more radical resection of the tumor was possible in a second surgery. Critically, a reorganization of motor language areas was demonstrated both with functional MRI and cortical stimulation. Furthermore, motor language areas were also identified in the right hemisphere, where previously they were absent. The patient's speech fluency improved both after stimulation and resection. We therefore demonstrate the first evidence of induced topographic plasticity using cHFCS in eloquent areas within a tumor, which allowed for increased tumor removal. Our results open the possibility to induce plasticity before the resection of brain tumors near eloquent areas, in order to increase the extent of resection.

Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy

PubMed Central

Booth, Clair A.; Witton, Jonathan; Nowacki, Jakub; Tsaneva-Atanasova, Krasimira; Jones, Matthew W.; Randall, Andrew D.

2016-01-01

The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. SIGNIFICANCE STATEMENT Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention. PMID:26758828

Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy.

PubMed

Booth, Clair A; Witton, Jonathan; Nowacki, Jakub; Tsaneva-Atanasova, Krasimira; Jones, Matthew W; Randall, Andrew D; Brown, Jonathan T

2016-01-13

The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention. Copyright © 2016 Booth, Witton et al.

A case of gait disturbance caused by low-dose gabapentin

PubMed Central

Kanao-Kanda, Megumi; Kanda, Hirotsugu; Takahata, Osamu; Kunisawa, Takayuki

2016-01-01

Gabapentin, an anticonvulsant agent, is now often used for the treatment of neuropathic pain all over the world. It is unclear whether the combined use of gabapentin, sodium valproate, and flunitrazepam results in enhancement of the side effect, a gait disturbance. A 60-year-old man was taking oral sodium valproate for symptomatic epilepsy after a brain contusion and flunitrazepam to relieve insomnia. Oral gabapentin therapy was started for suspected neuropathic pain. Although the initial dose of oral gabapentin (200 mg) relieved the pain, the lower extremities became weak, resulting in a gait disturbance. The therapy was restarted with a halved dose, and this resolved the gait disturbance and relieved the pain. PMID:27354808

Update of sleep alterations in depression

PubMed Central

Medina, Andrés Barrera; Lechuga, DeboraYoaly Arana; Escandón, Oscar Sánchez; Moctezuma, Javier Velázquez

2014-01-01

Sleep disturbances in depression are up to 70%. Patients frequently have difficulty in falling asleep, frequent awakenings during the night and non-restorative sleep. Sleep abnormalities in depression are mainly characterized by increased rapid eye movement (REM) sleep and reduced slow wave sleep. Among the mechanisms of sleep disturbances in depression are hyperactivation of the hypothalamic-pituitary-adrenal axis, CLOCK gene polymorphism and primary sleep disorders. The habenula is a structure regulating the activities of monoaminergic neurons in the brain. The hyperactivation of the habenula has also been implicated, together with sleep disturbances, in depression. The presence of depression in primary sleep disorders is common. Sleep disturbances treatment include pharmacotherapy or Cognitive Behavioral Therapy. PMID:26483922

[Sex differentiation of central nervous system--brain of man and woman].

PubMed

Arai, Yasumasa

2004-02-01

Sex differentiation of human brain is mostly dependent on the prenatal exposure to androgen(testosterone). Congenital aromatase deficiency does not disturb male brain development in men. This is quite different from experimental evidence from rodents whose brains need intraneuronal aromatization from androgen to estrogen to induce sex differentiation. There is evidence for male-female differences in brain structures. Some of them(INHA-3) appear to be related with sexual orientation. The other(BNST) might participate in forming gender-identity. In addition, sexually dimorphic features are recognized in some cognitive activities. The possible involvement of genetic factors in human brain sex differentiation is also discussed.

[Consequences of disturbed sex-hormone action in the central nervous system: behavioral, anatomical and functional changes].

PubMed

Kula, Krzysztof; Słowikowska-Hilczer, Jolanta

2003-01-01

Experimental studies revealed that transient action of sex steroids during perinatal period is crucial for the development of male sexual behavior and sexually dimorphic brain anatomy. Meanwhile, the lack of gonadal steroids in female foetus and estrogen effects at puberty determine female behavior together with female type of anatomical brain structures and of endocrine functions. In men psychic sex consists of gender identity (self-estimation), gender role (objective estimation of sex behavior). In addition, a sexual psycho-orientation (hetero-, bi- or homosexual) has been distinguished. Although it is believed that gender depends on the socio-environmental influences such as rearing, learning and individual choice, the biological factors are considered to be most important. This concept arises from recent study on patients with gender dysphoria syndrome (transsexualism). In intersexualism, in genetic men with disturbances of sexual differentiation of external genitalia because of the lack of testoterone production or action in peripheral tissues (male pseudohermaphroditism) or in genetic women with ambiguous genitalia because of the presence and action of androgens (female pseudohermaphroditism), a discordance between the formal sex (assigned after the birth) and the psychic gender may appear. In these individuals the legal sex established according to somatic and/or genetic sex at birth may be incompatible with their actual gender identity and role. The knowledge about gender identity is necessary at the decision of eventual (!) surgical correction of sex organs in patients with ambiguous genitalia. This decision should depend not on the expected, but on the actual gender identity of the individual patient. Meantime, early bilateral gonadectomy in patients with gonadal dysgenesis and male pseudohermaphroditism is an indication for life because of the highest risk of germ cell carcinoma.

Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies

PubMed Central

Shimamoto, Chie; Ohnishi, Tetsuo; Maekawa, Motoko; Watanabe, Akiko; Ohba, Hisako; Arai, Ryoichi; Iwayama, Yoshimi; Hisano, Yasuko; Toyota, Tomoko; Toyoshima, Manabu; Suzuki, Katsuaki; Shirayama, Yukihiko; Nakamura, Kazuhiko; Mori, Norio; Owada, Yuji; Kobayashi, Tetsuyuki; Yoshikawa, Takeo

2014-01-01

Disturbances of lipid metabolism have been implicated in psychiatric illnesses. We previously reported an association between the gene for fatty acid binding protein 7 (FABP7) and schizophrenia. Furthermore, we identified and reported several rare non-synonymous polymorphisms of the brain-expressed genes FABP3, FABP5 and FABP7 from schizophrenia and autism spectrum disorder (ASD), diseases known to part share genetic architecture. Here, we conducted further studies to better understand the contribution these genes make to the pathogenesis of schizophrenia and ASD. In postmortem brains, we detected altered mRNA expression levels of FABP5 in schizophrenia, and of FABP7 in ASD and altered FABP5 in peripheral lymphocytes. Using a patient cohort, comprehensive mutation screening identified six missense and two frameshift variants from the three FABP genes. The two frameshift proteins, FABP3 E132fs and FABP7 N80fs, formed cellular aggregates and were unstable when expressed in cultured cells. The four missense mutants with predicted possible damaging outcomes showed no changes in intracellular localization. Examining ligand binding properties, FABP7 S86G and FABP7 V126L lost their preference for docosahexaenoic acid to linoleic acid. Finally, mice deficient in Fabp3, Fabp5 and Fabp7 were evaluated in a systematic behavioral test battery. The Fabp3 knockout (KO) mice showed decreased social memory and novelty seeking, and Fabp7 KO mice displayed hyperactive and anxiety-related phenotypes, while Fabp5 KO mice showed no apparent phenotypes. In conclusion, disturbances in brain-expressed FABPs could represent an underlying disease mechanism in a proportion of schizophrenia and ASD sufferers. PMID:25027319

The influence of the great inequality on the secular disturbing function of the planetary system.

NASA Technical Reports Server (NTRS)

Musen, P.

1971-01-01

This paper derives the contribution by the great inequality to the secular disturbing function of the principal planets. Andoyer's expansion of the planetary disturbing function and von Zeipel's method of eliminating the periodic terms is employed; thereby, the corrected secular disturbing function for the planetary system is derived. The conclusion is drawn that the canonicity of the equations for the secular variation of the heliocentric elements can be preserved if there be retained, in the secular disturbing function, terms only of the second and fourth order relative to the eccentricity and inclinations. The Krylov-Bogoliubov method is suggested for eliminating periodic terms, if it is desired to include the secular perturbations of the fifth and higher order in the heliocentric elements. The additional part of the secular disturbing function derived in this paper can be included in existing theories of the secular effects of principal planets.

Brain regions associated with anosognosia for memory disturbance in Alzheimer's disease: a magnetic resonance imaging study.

PubMed

Fujimoto, Hiroshi; Matsuoka, Teruyuki; Kato, Yuka; Shibata, Keisuke; Nakamura, Kaeko; Yamada, Kei; Narumoto, Jin

2017-01-01

Patients with Alzheimer's disease (AD) are frequently unaware of their cognitive symptoms and medical diagnosis. The term "anosognosia" is used to indicate a general lack of awareness of one's disease or disorder. The neural substrate underlying anosognosia in AD is unclear. Since anosognosia for memory disturbance might be an initial sign of AD, it is important to determine the neural correlates. This study was designed to investigate the characteristics and neural correlates of anosognosia for memory disturbance in patients with mild AD. The subjects were 49 patients with mild AD who participated in a retrospective cross-sectional study. None of the patients had been treated with cholinesterase inhibitors, memantine, or psychotropic drugs. All patients underwent magnetic resonance imaging (MRI). Anosognosia for memory disturbance was assessed based on the discrepancy between questionnaire scores of patients and their caregivers. Structural MRI data were analyzed to explore the association between anosognosia and brain atrophy, using a voxel-based approach. Statistical parametric mapping software was used to explore neural correlations. In image analysis, multiple regression analysis was performed to examine the relationship between anosognosia score and regional gray matter volume. Age, years of education, and total intracranial volume were entered as covariates. The anosognosia score for memory disturbance was significantly negatively correlated with gray matter volume in the left superior frontal gyrus. The left superior frontal gyrus was involved in anosognosia for memory disturbance, while the medial temporal lobe, which is usually damaged in mild AD, was not associated with anosognosia. The left superior frontal gyrus might be an important region for anosognosia in mild AD.

Decoding Pedophilia: Increased Anterior Insula Response to Infant Animal Pictures

PubMed Central

Ponseti, Jorge; Bruhn, Daniel; Nolting, Julia; Gerwinn, Hannah; Pohl, Alexander; Stirn, Aglaja; Granert, Oliver; Laufs, Helmut; Deuschl, Günther; Wolff, Stephan; Jansen, Olav; Siebner, Hartwig; Briken, Peer; Mohnke, Sebastian; Amelung, Till; Kneer, Jonas; Schiffer, Boris; Walter, Henrik; Kruger, Tillmann H. C.

2018-01-01

Previous research found increased brain responses of men with sexual interest in children (i.e., pedophiles) not only to pictures of naked children but also to pictures of child faces. This opens the possibly that pedophilia is linked (in addition to or instead of an aberrant sexual system) to an over-active nurturing system. To test this hypothesis we exposed pedophiles and healthy controls to pictures of infant and adult animals during functional magnetic resonance imaging of the brain. By using pictures of infant animals (instead of human infants), we aimed to elicit nurturing processing without triggering sexual processing. We hypothesized that elevated brain responses to nurturing stimuli will be found – in addition to other brain areas – in the anterior insula of pedophiles because this area was repeatedly found to be activated when adults see pictures of babies. Behavioral ratings confirmed that pictures of infant or adult animals were not perceived as sexually arousing neither by the pedophilic participants nor by the heathy controls. Statistical analysis was applied to the whole brain as well as to the anterior insula as region of interest. Only in pedophiles did infants relative to adult animals increase brain activity in the anterior insula, supplementary motor cortex, and dorsolateral prefrontal areas. Within-group analysis revealed an increased brain response to infant animals in the left anterior insular cortex of the pedophilic participants. Currently, pedophilia is considered the consequence of disturbed sexual or executive brain processing, but details are far from known. The present findings raise the question whether there is also an over-responsive nurturing system in pedophilia. PMID:29403367

LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-β.

PubMed

Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

2012-11-14

Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer's disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA.

Decoding Pedophilia: Increased Anterior Insula Response to Infant Animal Pictures.

PubMed

Ponseti, Jorge; Bruhn, Daniel; Nolting, Julia; Gerwinn, Hannah; Pohl, Alexander; Stirn, Aglaja; Granert, Oliver; Laufs, Helmut; Deuschl, Günther; Wolff, Stephan; Jansen, Olav; Siebner, Hartwig; Briken, Peer; Mohnke, Sebastian; Amelung, Till; Kneer, Jonas; Schiffer, Boris; Walter, Henrik; Kruger, Tillmann H C

2017-01-01

Previous research found increased brain responses of men with sexual interest in children (i.e., pedophiles) not only to pictures of naked children but also to pictures of child faces. This opens the possibly that pedophilia is linked (in addition to or instead of an aberrant sexual system) to an over-active nurturing system. To test this hypothesis we exposed pedophiles and healthy controls to pictures of infant and adult animals during functional magnetic resonance imaging of the brain. By using pictures of infant animals (instead of human infants), we aimed to elicit nurturing processing without triggering sexual processing. We hypothesized that elevated brain responses to nurturing stimuli will be found - in addition to other brain areas - in the anterior insula of pedophiles because this area was repeatedly found to be activated when adults see pictures of babies. Behavioral ratings confirmed that pictures of infant or adult animals were not perceived as sexually arousing neither by the pedophilic participants nor by the heathy controls. Statistical analysis was applied to the whole brain as well as to the anterior insula as region of interest. Only in pedophiles did infants relative to adult animals increase brain activity in the anterior insula, supplementary motor cortex, and dorsolateral prefrontal areas. Within-group analysis revealed an increased brain response to infant animals in the left anterior insular cortex of the pedophilic participants. Currently, pedophilia is considered the consequence of disturbed sexual or executive brain processing, but details are far from known. The present findings raise the question whether there is also an over-responsive nurturing system in pedophilia.

cis-4-Decenoic and decanoic acids impair mitochondrial energy, redox and Ca(2+) homeostasis and induce mitochondrial permeability transition pore opening in rat brain and liver: Possible implications for the pathogenesis of MCAD deficiency.

PubMed

Amaral, Alexandre Umpierrez; Cecatto, Cristiane; da Silva, Janaína Camacho; Wajner, Alessandro; Godoy, Kálita Dos Santos; Ribeiro, Rafael Teixeira; Wajner, Moacir

2016-09-01

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is biochemically characterized by tissue accumulation of octanoic (OA), decanoic (DA) and cis-4-decenoic (cDA) acids, as well as by their carnitine by-products. Untreated patients present episodic encephalopathic crises and biochemical liver alterations, whose pathophysiology is poorly known. We investigated the effects of OA, DA, cDA, octanoylcarnitine (OC) and decanoylcarnitine (DC) on critical mitochondrial functions in rat brain and liver. DA and cDA increased resting respiration and diminished ADP- and CCCP-stimulated respiration and complexes II-III and IV activities in both tissues. The data indicate that these compounds behave as uncouplers and metabolic inhibitors of oxidative phosphorylation. Noteworthy, metabolic inhibition was more evident in brain as compared to liver. DA and cDA also markedly decreased mitochondrial membrane potential, NAD(P)H content and Ca(2+) retention capacity in Ca(2+)-loaded brain and liver mitochondria. The reduction of Ca(2+) retention capacity was more pronounced in liver and totally prevented by cyclosporine A and ADP, as well as by ruthenium red, demonstrating the involvement of mitochondrial permeability transition (mPT) and Ca(2+). Furthermore, cDA induced lipid peroxidation in brain and liver mitochondria and increased hydrogen peroxide formation in brain, suggesting the participation of oxidative damage in cDA-induced alterations. Interestingly, OA, OC and DC did not alter the evaluated parameters, implying lower toxicity for these compounds. Our results suggest that DA and cDA, in contrast to OA and medium-chain acylcarnitines, disturb important mitochondrial functions in brain and liver by multiple mechanisms that are possibly involved in the neuropathology and liver alterations observed in MCAD deficiency. Copyright © 2016 Elsevier B.V. All rights reserved.

Riboflavin and migraine: the bridge over troubled mitochondria.

PubMed

Colombo, Bruno; Saraceno, Lorenzo; Comi, Giancarlo

2014-05-01

Brain energy metabolism has been found to be disturbed in migraine. A mitochondrial defect may reduce the threshold for migraine attacks both increasing neuronal excitability and leading migrainous brain to a hyper-responsiveness to triggering stimuli. Riboflavin, a major co-factor in oxidative metabolism, may overcome this impairment. RCT studies in adult confirmed that riboflavin is safe and probably effective in migraine prophylaxis, based on level B evidence. Improving brain energy metabolism may reduce the susceptibility to migraine when brain energy demand increases due to both physiological and biopsychological factors.

CNNM2 Mutations Cause Impaired Brain Development and Seizures in Patients with Hypomagnesemia

PubMed Central

Lameris, Anke L. L.; van Wijk, Erwin; Flik, Gert; Regele, Sabrina; Korenke, G. Christoph; Neophytou, Birgit; Rust, Stephan; Reintjes, Nadine; Konrad, Martin; Bindels, René J. M.; Hoenderop, Joost G. J.

2014-01-01

Intellectual disability and seizures are frequently associated with hypomagnesemia and have an important genetic component. However, to find the genetic origin of intellectual disability and seizures often remains challenging because of considerable genetic heterogeneity and clinical variability. In this study, we have identified new mutations in CNNM2 in five families suffering from mental retardation, seizures, and hypomagnesemia. For the first time, a recessive mode of inheritance of CNNM2 mutations was observed. Importantly, patients with recessive CNNM2 mutations suffer from brain malformations and severe intellectual disability. Additionally, three patients with moderate mental disability were shown to carry de novo heterozygous missense mutations in the CNNM2 gene. To elucidate the physiological role of CNNM2 and explain the pathomechanisms of disease, we studied CNNM2 function combining in vitro activity assays and the zebrafish knockdown model system. Using stable Mg2+ isotopes, we demonstrated that CNNM2 increases cellular Mg2+ uptake in HEK293 cells and that this process occurs through regulation of the Mg2+-permeable cation channel TRPM7. In contrast, cells expressing mutated CNNM2 proteins did not show increased Mg2+ uptake. Knockdown of cnnm2 isoforms in zebrafish resulted in disturbed brain development including neurodevelopmental impairments such as increased embryonic spontaneous contractions and weak touch-evoked escape behaviour, and reduced body Mg content, indicative of impaired renal Mg2+ absorption. These phenotypes were rescued by injection of mammalian wild-type Cnnm2 cRNA, whereas mammalian mutant Cnnm2 cRNA did not improve the zebrafish knockdown phenotypes. We therefore concluded that CNNM2 is fundamental for brain development, neurological functioning and Mg2+ homeostasis. By establishing the loss-of-function zebrafish model for CNNM2 genetic disease, we provide a unique system for testing therapeutic drugs targeting CNNM2 and for monitoring their effects on the brain and kidney phenotype. PMID:24699222

Language disturbance and functioning in first episode psychosis.

PubMed

Roche, Eric; Segurado, Ricardo; Renwick, Laoise; McClenaghan, Aisling; Sexton, Sarah; Frawley, Timothy; Chan, Carol K; Bonar, Maurice; Clarke, Mary

2016-01-30

Language disturbance has a central role in the presentation of psychotic disorders however its relationship with functioning requires further clarification, particularly in first episode psychosis (FEP). Both language disturbance and functioning can be evaluated with clinician-rated and performance-based measures. We aimed to investigate the concurrent association between clinician-rated and performance-based measures of language disturbance and functioning in FEP. We assessed 108 individuals presenting to an Early Intervention in Psychosis Service in Ireland. Formal thought disorder (FTD) dimensions and bizarre idiosyncratic thinking (BIT) were rated with structured assessment tools. Functioning was evaluated with a performance-based instrument, a clinician-rated measure and indicators of real-world functioning. The disorganisation dimension of FTD was significantly associated with clinician-rated measures of occupational and social functioning (Beta=-0.19, P<0.05 and Beta=-0.31, P<0.01, respectively). BIT was significantly associated with the performance-based measure of functioning (Beta=-0.22, P<0.05). Language disturbance was of less value in predicting real-world measures of functioning. Clinician-rated and performance-based assessments of language disturbance are complementary and each has differential associations with functioning. Communication disorders should be considered as a potential target for intervention in FEP, although further evaluation of the longitudinal relationship between language disturbance and functioning should be undertaken. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Neuronal DNA Methylation Profiling of Blast-Related Traumatic Brain Injury.

PubMed

Haghighi, Fatemeh; Ge, Yongchao; Chen, Sean; Xin, Yurong; Umali, Michelle U; De Gasperi, Rita; Gama Sosa, Miguel A; Ahlers, Stephen T; Elder, Gregory A

2015-08-15

Long-term molecular changes in the brain resulting from blast exposure may be mediated by epigenetic changes, such as deoxyribonucleic acid (DNA) methylation, that regulate gene expression. Aberrant regulation of gene expression is associated with behavioral abnormalities, where DNA methylation bridges environmental signals to sustained changes in gene expression. We assessed DNA methylation changes in the brains of rats exposed to three 74.5 kPa blast overpressure events, conditions that have been associated with long-term anxiogenic manifestations weeks or months following the initial exposures. Rat frontal cortex eight months post-exposure was used for cell sorting of whole brain tissue into neurons and glia. We interrogated DNA methylation profiles in these cells using Expanded Reduced Representation Bisulfite Sequencing. We obtained data for millions of cytosines, showing distinct methylation profiles for neurons and glia and an increase in global methylation in neuronal versus glial cells (p<10(-7)). We detected DNA methylation perturbations in blast overpressure-exposed animals, compared with sham blast controls, within 458 and 379 genes in neurons and glia, respectively. Differentially methylated neuronal genes showed enrichment in cell death and survival and nervous system development and function, including genes involved in transforming growth factor β and nitric oxide signaling. Functional validation via gene expression analysis of 30 differentially methylated neuronal and glial genes showed a 1.2 fold change in gene expression of the serotonin N-acetyltransferase gene (Aanat) in blast animals (p<0.05). These data provide the first genome-based evidence for changes in DNA methylation induced in response to multiple blast overpressure exposures. In particular, increased methylation and decreased gene expression were observed in the Aanat gene, which is involved in converting serotonin to the circadian hormone melatonin and is implicated in sleep disturbance and depression associated with traumatic brain injury.

Dopaminergic neuronal injury in the adult rat brain following neonatal exposure to lipopolysaccharide and the silent neurotoxicity

PubMed Central

Fan, Lir-Wan; Tien, Lu-Tai; Zheng, Baoying; Pang, Yi; Lin, Rick C. S.; Simpson, Kimberly L.; Ma, Tangeng; Rhodes, Philip G.; Cai, Zhengwei

2010-01-01

Our previous studies have shown that neonatal exposure to lipopolysaccharide (LPS) resulted in motor dysfunction and dopaminergic neuronal injury in the juvenile rat brain. To further examine whether neonatal LPS exposure has persisting effects in adult rats, motor behaviors were examined from postnatal day 7 (P7) to P70 and brain injury was determined in P70 rats following an intracerebral injection of LPS (1 mg/kg) in P5 Sprague-Dawley male rats. Although neonatal LPS exposure resulted in hyperactivity in locomotion and stereotyped tasks, and other disturbances of motor behaviors, the impaired motor functions were spontaneously recovered by P70. On the other hand, neonatal LPS-induced injury to the dopaminergic system such as the loss of dendrites and reduced tyrosine hydroxylase immunoreactivity in the substantia nigra persisted in P70 rats. Neonatal LPS exposure also resulted in sustained inflammatory responses in the P70 rat brain, as indicated by an increased number of activated microglia and elevation of interleukin-1β and interleukin-6 content in the rat brain. In addition, when challenged with methamphetamine (METH, 0.5 mg/kg) subcutaneously, rats with neonatal LPS exposure had significantly increased responses in METH-induced locomotion and stereotypy behaviors as compared to those without LPS exposure. These results indicate that although neonatal LPS-induced neurobehavioral impairment is spontaneously recoverable, the LPS exposure-induced persistent injury to the dopaminergic system and the chronic inflammation may represent the existence of silent neurotoxicity. Our data further suggest that the compromised dendritic mitochondrial function might contribute, at least partially, to the silent neurotoxicity. PMID:20875849

Drug discovery based on genetic and metabolic findings in schizophrenia.

PubMed

Dwyer, Donard S; Weeks, Kathrine; Aamodt, Eric J

2008-11-01

Recent progress in the genetics of schizophrenia provides the rationale for re-evaluating causative factors and therapeutic strategies for this disease. Here, we review the major candidate susceptibility genes and relate the aberrant function of these genes to defective regulation of energy metabolism in the schizophrenic brain. Disturbances in energy metabolism potentially lead to neurodevelopmental deficits, impaired function of the mature nervous system and failure to maintain neurites/dendrites and synaptic connections. Current antipsychotic drugs do not specifically address these underlying deficits; therefore, a new generation of more effective medications is urgently needed. Novel targets for future drug discovery are identified in this review. The coordinated application of structure-based drug design, systems biology and research on model organisms may greatly facilitate the search for next-generation antipsychotic drugs.

CELECOXIB ATTENUATES SYSTEMIC LIPOPOLYSACCHARIDE-INDUCED BRAIN INFLAMMATION AND WHITE MATTER INJURY IN THE NEONATAL RATS

PubMed Central

FAN, L.-W.; KAIZAKI, A.; TIEN, L.-T.; PANG, Y.; TANAKA, S.; NUMAZAWA, S.; BHATT, A. J.; CAI, Z.

2013-01-01

Lipopolysaccharide (LPS)-induced white matter injury in the neonatal rat brain is associated with inflammatory processes. Cyclooxygenase-2 (COX-2) can be induced by inflammatory stimuli, such as cytokines and pro-inflammatory molecules, suggesting that COX-2 may be considered as the target for anti-inflammation. The objective of the present study was to examine whether celecoxib, a selective COX-2 inhibitor, can reduce systemic LPS-induced brain inflammation and brain damage. Intraperitoneal (i.p.) injection of LPS (2 mg/kg) was performed in postnatal day 5 (P5) of Sprague-Dawley rat pups and celecoxib (20 mg/kg) or vehicle was administered i.p. 5 min after LPS injection. The body weight and wire hanging maneuver test were performed 24 hr after the LPS exposure, and brain injury was examined after these tests. Systemic LPS exposure resulted in an impairment of behavioral performance and acute brain injury, as indicated by apoptotic death of oligodendrocytes (OLs) and loss of OL immunoreactivity in the neonatal rat brain. Treatments with celecoxib significantly reduced systemic LPS-induced neurobehavioral disturbance and brain damage. Celecoxib administration significantly attenuated systemic LPS-induced increments in the number of activated microglia and astrocytes, concentrations of IL-1β and TNFα, and protein levels of phosphorylated-p38 MAPK in the neonatal rat brain. The protection of celecoxib was also associated with a reduction of systemic LPS-induced COX-2+ cells which were double labeled with GFAP+ (astrocyte) cells. The overall results suggest that celecoxib was capable of attenuating the brain injury and neurobehavioral disturbance induced by systemic LPS exposure, and the protective effects are associated with its anti-inflammatory properties. PMID:23485816

[Neuroanatomical, genetic and neurochemical aspects of infantile autism].

PubMed

Gerhant, Aneta; Olajossy, Marcin; Olajossy-Hilkesberger, Luiza

2013-01-01

Infantile autism is a neurodevelopmental disorder characterized by impairments in communication, reciprocal social interaction and restricted repetitive behaviors or interests. Although the cause of these disorders is not yet known, studies strongly suggest a genetic basis with a complex mode of inheritance. The etiopathogenetic processes of autism are extremely complex, which is reflected in the varying course and its symptomatology. Trajectories of brain development and volumes of its structures are aberrant in autistic patients. It is suggested that disturbances in sertotoninergic, gabaergic, glutaminergic, cholinergic and dopaminergic neurotransmission can be responsible for symptoms of autism as well as can disturb the development of the young brain. The objective of this article is to present the results of reasearch on neuroanatomical, neurochemical and genetic aspects of autism.

Brain limbic system-based intelligent controller application to lane change manoeuvre

NASA Astrophysics Data System (ADS)

Kim, Changwon; Langari, Reza

2011-12-01

This paper presents the application of a novel neuromorphic control strategy for lane change manoeuvres in the highway environment. The lateral dynamics of a vehicle with and without wind disturbance are derived and utilised to implement a control strategy based on the brain limbic system. To show the robustness of the proposed controller, several disturbance conditions including wind, uncertainty in the cornering stiffness, and changes in the vehicle mass are investigated. To demonstrate the performance of the suggested strategy, simulation results of the proposed method are compared with the human driver model-based control scheme, which has been discussed in the literature. The simulation results demonstrate the superiority of the proposed controller in energy efficiency, driving comfort, and robustness.

Disturbance by an endemic rodent in an arid shrubland is a habitat filter: effects on plant invasion and taxonomical, functional and phylogenetic community structure.

PubMed

Escobedo, Víctor M; Rios, Rodrigo S; Salgado-Luarte, Cristian; Stotz, Gisela C; Gianoli, Ernesto

2017-03-01

Disturbance often drives plant invasion and may modify community assembly. However, little is known about how these modifications of community patterns occur in terms of taxonomic, functional and phylogenetic structure. This study evaluated in an arid shrubland the influence of disturbance by an endemic rodent on community functional divergence and phylogenetic structure as well as on plant invasion. It was expected that disturbance would operate as a habitat filter favouring exotic species with short life cycles. Sixteen plots were sampled along a disturbance gradient caused by the endemic fossorial rodent Spalacopus cyanus , measuring community parameters and estimating functional divergence for life history traits (functional dispersion index) and the relative contribution to functional divergence of exotic and native species. The phylogenetic signal (Pagel's lambda) and phylogenetic community structure (mean phylogenetic distance and mean nearest taxon phylogenetic distance) were also estimated. The use of a continuous approach to the disturbance gradient allowed the identification of non-linear relationships between disturbance and community parameters. The relationship between disturbance and both species richness and abundance was positive for exotic species and negative for native species. Disturbance modified community composition, and exotic species were associated with more disturbed sites. Disturbance increased trait convergence, which resulted in phylogenetic clustering because traits showed a significant phylogenetic signal. The relative contribution of exotic species to functional divergence increased, while that of natives decreased, with disturbance. Exotic and native species were not phylogenetically distinct. Disturbance by rodents in this arid shrubland constitutes a habitat filter over phylogeny-dependent life history traits, leading to phylogenetic clustering, and drives invasion by favouring species with short life cycles. Results can be explained by high phenotypic and phylogenetic resemblance between exotic and native species. The use of continuous gradients when studying the effects of disturbance on community assembly is advocated. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Gut-brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease.

PubMed

Abautret-Daly, Áine; Dempsey, Elaine; Parra-Blanco, Adolfo; Medina, Carlos; Harkin, Andrew

2017-03-08

Introduction Inflammatory bowel disease (IBD) is a chronic relapsing and remitting disorder characterised by inflammation of the gastrointestinal tract. There is a growing consensus that IBD is associated with anxiety- and depression-related symptoms. Psychological symptoms appear to be more prevalent during active disease states with no difference in prevalence between Crohn's disease and ulcerative colitis. Behavioural disturbances including anxiety- and depression-like symptoms have also been observed in animal models of IBD. The likely mechanisms underlying the association are discussed with particular reference to communication between the gut and brain. The close bidirectional relationship known as the gut-brain axis includes neural, hormonal and immune communication links. Evidence is provided for a number of interacting factors including activation of the inflammatory response system in the brain, the hypothalamic-pituitary-adrenal axis, and brain areas implicated in altered behaviours, changes in blood brain barrier integrity, and an emerging role for gut microbiota and response to probiotics in IBD. Discussion The impact of psychological stress in models of IBD remains somewhat conflicted, however, it is weighted in favour of stress or early stressful life events as risk factors in the development of IBD, stress-induced exacerbation of inflammation and relapse. It is recommended that patients with IBD be screened for psychological disturbance and treated accordingly as intervention can improve quality of life and may reduce relapse rates.

Dysfunction of sensory oscillations in Autism Spectrum Disorder

PubMed Central

Simon, David M.; Wallace, Mark T.

2016-01-01

Autism Spectrum Disorder (ASD) is a highly prevalent developmental disability characterized by deficits in social communication and interaction, restricted interests, and repetitive behaviors. Recently, anomalous sensory and perceptual function has gained an increased level of recognition as an important feature of ASD. A specific impairment in the ability to integrate information across brain networks has been proposed to contribute to these disruptions. A crucial mechanism for these integrative processes is the rhythmic synchronization of neuronal excitability across neural populations; collectively known as oscillations. In ASD there is believed to be a deficit in the ability to efficiently couple functional neural networks using these oscillations. This review discusses evidence for disruptions in oscillatory synchronization in ASD, and how disturbance of this neural mechanism contributes to alterations in sensory and perceptual function. The review also frames oscillatory data from the perspective of prevailing neurobiologically-inspired theories of ASD. PMID:27451342

Adolescent brain maturation, the endogenous cannabinoid system and the neurobiology of cannabis-induced schizophrenia.

PubMed

Bossong, Matthijs G; Niesink, Raymond J M

2010-11-01

Cannabis use during adolescence increases the risk of developing psychotic disorders later in life. However, the neurobiological processes underlying this relationship are unknown. This review reports the results of a literature search comprising various neurobiological disciplines, ultimately converging into a model that might explain the neurobiology of cannabis-induced schizophrenia. The article briefly reviews current insights into brain development during adolescence. In particular, the role of the excitatory neurotransmitter glutamate in experience-dependent maturation of specific cortical circuitries is examined. The review also covers recent hypotheses regarding disturbances in strengthening and pruning of synaptic connections in the prefrontal cortex, and the link with latent psychotic disorders. In the present model, cannabis-induced schizophrenia is considered to be a distortion of normal late postnatal brain maturation. Distortion of glutamatergic transmission during critical periods may disturb prefrontal neurocircuitry in specific brain areas. Our model postulates that adolescent exposure to Δ9-tetrahydrocannabinol (THC), the primary psychoactive substance in cannabis, transiently disturbs physiological control of the endogenous cannabinoid system over glutamate and GABA release. As a result, THC may adversely affect adolescent experience-dependent maturation of neural circuitries within prefrontal cortical areas. Depending on dose, exact time window and duration of exposure, this may ultimately lead to the development of psychosis or schizophrenia. The proposed model provides testable hypotheses which can be addressed in future studies, including animal experiments, reanalysis of existing epidemiological data, and prospective epidemiological studies in which the role of the dose-time-effect relationship should be central. Copyright © 2010 Elsevier Ltd. All rights reserved.

Emerging Viral Infections in Sub-Saharan Africa and the Developing Nervous System: A Mini Review.

PubMed

Kakooza-Mwesige, Angelina; Mohammed, Abdul H; Kristensson, Krister; Juliano, Sharon L; Lutwama, Julius J

2018-01-01

The global public health concern is heightened over the increasing number of emerging viruses, i.e., newly discovered or previously known that have expanded into new geographical zones. These viruses challenge the health-care systems in sub-Saharan Africa (SSA) countries from which several of them have originated and been transmitted by insects worldwide. Some of these viruses are neuroinvasive, but have been relatively neglected by neuroscientists. They may provide experiments by nature to give a time window for exposure to a new virus within sizeable, previously non-infected human populations, which, for instance, enables studies on potential long-term or late-onset effects on the developing nervous system. Here, we briefly summarize studies on the developing brain by West Nile, Zika, and Chikungunya viruses, which are mosquito-borne and have spread worldwide out of SSA. They can all be neuroinvasive, but their effects vary from malformations caused by prenatal infections to cognitive disturbances following perinatal or later infections. We also highlight Ebola virus, which can leave surviving children with psychiatric disturbances and cause persistent infections in the non-human primate brain. Greater awareness within the neuroscience community is needed to emphasize the menace evoked by these emerging viruses to the developing brain. In particular, frontline neuroscience research should include neuropediatric follow-up studies in the field on long-term or late-onset cognitive and behavior disturbances or neuropsychiatric disorders. Studies on pathogenetic mechanisms for viral-induced perturbations of brain maturation should be extended to the vulnerable periods when neurocircuit formations are at peaks during infancy and early childhood.

Emerging Viral Infections in Sub-Saharan Africa and the Developing Nervous System: A Mini Review

PubMed Central

Kakooza-Mwesige, Angelina; Mohammed, Abdul H.; Kristensson, Krister; Juliano, Sharon L.; Lutwama, Julius J.

2018-01-01

The global public health concern is heightened over the increasing number of emerging viruses, i.e., newly discovered or previously known that have expanded into new geographical zones. These viruses challenge the health-care systems in sub-Saharan Africa (SSA) countries from which several of them have originated and been transmitted by insects worldwide. Some of these viruses are neuroinvasive, but have been relatively neglected by neuroscientists. They may provide experiments by nature to give a time window for exposure to a new virus within sizeable, previously non-infected human populations, which, for instance, enables studies on potential long-term or late-onset effects on the developing nervous system. Here, we briefly summarize studies on the developing brain by West Nile, Zika, and Chikungunya viruses, which are mosquito-borne and have spread worldwide out of SSA. They can all be neuroinvasive, but their effects vary from malformations caused by prenatal infections to cognitive disturbances following perinatal or later infections. We also highlight Ebola virus, which can leave surviving children with psychiatric disturbances and cause persistent infections in the non-human primate brain. Greater awareness within the neuroscience community is needed to emphasize the menace evoked by these emerging viruses to the developing brain. In particular, frontline neuroscience research should include neuropediatric follow-up studies in the field on long-term or late-onset cognitive and behavior disturbances or neuropsychiatric disorders. Studies on pathogenetic mechanisms for viral-induced perturbations of brain maturation should be extended to the vulnerable periods when neurocircuit formations are at peaks during infancy and early childhood. PMID:29527187

Prototype of an opto-capacitive probe for non-invasive sensing cerebrospinal fluid circulation

NASA Astrophysics Data System (ADS)

Myllylä, Teemu; Vihriälä, Erkki; Pedone, Matteo; Korhonen, Vesa; Surazynski, Lukasz; Wróbel, Maciej; Zienkiewicz, Aleksandra; Hakala, Jaakko; Sorvoja, Hannu; Lauri, Janne; Fabritius, Tapio; Jedrzejewska-Szczerska, Małgorzata; Kiviniemi, Vesa; Meglinski, Igor

2017-03-01

In brain studies, the function of the cerebrospinal fluid (CSF) awakes growing interest, particularly related to studies of the glymphatic system in the brain, which is connected with the complex system of lymphatic vessels responsible for cleaning the tissues. The CSF is a clear, colourless liquid including water (H2O) approximately with a concentration of 99 %. In addition, it contains electrolytes, amino acids, glucose, and other small molecules found in plasma. The CSF acts as a cushion behind the skull, providing basic mechanical as well as immunological protection to the brain. Disturbances of the CSF circulation have been linked to several brain related medical disorders, such as dementia. Our goal is to develop an in vivo method for the non-invasive measurement of cerebral blood flow and CSF circulation by exploiting optical and capacitive sensing techniques simultaneously. We introduce a prototype of a wearable probe that is aimed to be used for long-term brain monitoring purposes, especially focusing on studies of the glymphatic system. In this method, changes in cerebral blood flow, particularly oxy- and deoxyhaemoglobin, are measured simultaneously and analysed with the response gathered by the capacitive sensor in order to distinct the dynamics of the CSF circulation behind the skull. Presented prototype probe is tested by measuring liquid flows inside phantoms mimicking the CSF circulation.

Cognitive, affective, and conative theory of mind (ToM) in children with traumatic brain injury.

PubMed

Dennis, Maureen; Simic, Nevena; Bigler, Erin D; Abildskov, Tracy; Agostino, Alba; Taylor, H Gerry; Rubin, Kenneth; Vannatta, Kathryn; Gerhardt, Cynthia A; Stancin, Terry; Yeates, Keith Owen

2013-07-01

We studied three forms of dyadic communication involving theory of mind (ToM) in 82 children with traumatic brain injury (TBI) and 61 children with orthopedic injury (OI): Cognitive (concerned with false belief), Affective (concerned with expressing socially deceptive facial expressions), and Conative (concerned with influencing another's thoughts or feelings). We analyzed the pattern of brain lesions in the TBI group and conducted voxel-based morphometry for all participants in five large-scale functional brain networks, and related lesion and volumetric data to ToM outcomes. Children with TBI exhibited difficulty with Cognitive, Affective, and Conative ToM. The perturbation threshold for Cognitive ToM is higher than that for Affective and Conative ToM, in that Severe TBI disturbs Cognitive ToM but even Mild-Moderate TBI disrupt Affective and Conative ToM. Childhood TBI was associated with damage to all five large-scale brain networks. Lesions in the Mirror Neuron Empathy network predicted lower Conative ToM involving ironic criticism and empathic praise. Conative ToM was significantly and positively related to the package of Default Mode, Central Executive, and Mirror Neuron Empathy networks and, more specifically, to two hubs of the Default Mode Network, the posterior cingulate/retrosplenial cortex and the hippocampal formation, including entorhinal cortex and parahippocampal cortex. Copyright © 2012 Elsevier Ltd. All rights reserved.

"Missing links" in borderline personality disorder: loss of neural synchrony relates to lack of emotion regulation and impulse control.

PubMed

Williams, Leanne M; Sidis, Anna; Gordon, Evian; Meares, Russell A

2006-05-01

Symptoms of borderline personality disorder (BPD) may reflect distinct breakdowns in the integration of posterior and frontal brain networks. We used a high temporal resolution measure (40-Hz gamma phase synchrony) of brain activity to examine the connectivity of brain function in BPD. Unmedicated patients with BPD (n = 15) and age-and sex-matched healthy control subjects (n = 15) undertook a task requiring discrimination of salient from background tones. In response to salient stimuli, the magnitude and latency of peak gamma phase synchrony for early (0-150 ms post stimulus) and late (250-500 ms post stimulus) phases were calculated for frontal and posterior regions and for left and right hemispheres. We recorded skin conductance responses (SCRs) and reaction time (RT) simultaneously to examine the contribution of arousal and performance. Compared with controls, patients with BPD had a significant delay in early posterior gamma synchrony and a reduction in right hemisphere late gamma synchrony in response to salient stimuli. Both SCR onset and RT were also delayed in BPD, but independently from differences in synchrony. The delay in posterior synchrony was associated with cognitive symptoms, and reduced right hemisphere synchrony was associated with impulsivity. These findings suggest that distinct impairments in the functional connectivity of neural systems for orienting to salient input underlie core dimensions of cognitive disturbance and poor impulse control in BPD.

Abnormal metabolic brain networks in Parkinson's disease from blackboard to bedside.

PubMed

Tang, Chris C; Eidelberg, David

2010-01-01

Metabolic imaging in the rest state has provided valuable information concerning the abnormalities of regional brain function that underlie idiopathic Parkinson's disease (PD). Moreover, network modeling procedures, such as spatial covariance analysis, have further allowed for the quantification of these changes at the systems level. In recent years, we have utilized this strategy to identify and validate three discrete metabolic networks in PD associated with the motor and cognitive manifestations of the disease. In this chapter, we will review and compare the specific functional topographies underlying parkinsonian akinesia/rigidity, tremor, and cognitive disturbance. While network activity progressed over time, the rate of change for each pattern was distinctive and paralleled the development of the corresponding clinical symptoms in early-stage patients. This approach is already showing great promise in identifying individuals with prodromal manifestations of PD and in assessing the rate of progression before clinical onset. Network modulation was found to correlate with the clinical effects of dopaminergic treatment and surgical interventions, such as subthalamic nucleus (STN) deep brain stimulation (DBS) and gene therapy. Abnormal metabolic networks have also been identified for atypical parkinsonian syndromes, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Using multiple disease-related networks for PD, MSA, and PSP, we have developed a novel, fully automated algorithm for accurate classification at the single-patient level, even at early disease stages. Copyright © 2010 Elsevier B.V. All rights reserved.

Is the ADHD brain wired differently? A review on structural and functional connectivity in attention deficit hyperactivity disorder.

PubMed

Konrad, Kerstin; Eickhoff, Simon B

2010-06-01

In recent years, a change in perspective in etiological models of attention deficit hyperactivity disorder (ADHD) has occurred in concordance with emerging concepts in other neuropsychiatric disorders such as schizophrenia and autism. These models shift the focus of the assumed pathology from regional brain abnormalities to dysfunction in distributed network organization. In the current contribution, we report findings from functional connectivity studies during resting and task states, as well as from studies on structural connectivity using diffusion tensor imaging, in subjects with ADHD. Although major methodological limitations in analyzing connectivity measures derived from noninvasive in vivo neuroimaging still exist, there is convergent evidence for white matter pathology and disrupted anatomical connectivity in ADHD. In addition, dysfunctional connectivity during rest and during cognitive tasks has been demonstrated. However, the causality between disturbed white matter architecture and cortical dysfunction remains to be evaluated. Both genetic and environmental factors might contribute to disruptions in interactions between different brain regions. Stimulant medication not only modulates regionally specific activation strength but also normalizes dysfunctional connectivity, pointing to a predominant network dysfunction in ADHD. By combining a longitudinal approach with a systems perspective in ADHD in the future, it might be possible to identify at which stage during development disruptions in neural networks emerge and to delineate possible new endophenotypes of ADHD. (c) 2010 Wiley-Liss, Inc.

Hormonal contraceptives suppress oxytocin-induced brain reward responses to the partner's face.

PubMed

Scheele, Dirk; Plota, Jessica; Stoffel-Wagner, Birgit; Maier, Wolfgang; Hurlemann, René

2016-05-01

The hypothalamic peptide oxytocin (OXT) has been identified as a key modulator of pair-bonding in men, but its effects in women are still elusive. Moreover, there is substantial evidence that hormonal contraception (HC) influences partner preferences and sexual satisfaction, which constitute core domains of OXT function. We thus hypothesized that OXT effects on partner-related behavioral and neural responses could be significantly altered in women using HC. In this functional magnetic resonance imaging study involving 40 pair-bonded women, 21 of whom were using HC, we investigated whether a 24-IU nasal dose of OXT would modulate brain reward responses evoked by the romantic partner's face relative to the faces of familiar and unfamiliar people. Treatment with OXT increased the perceived attractiveness of the partner relative to other men, which was paralleled by elevated responses in reward-associated regions, including the nucleus accumbens. These effects of OXT were absent in women using HC. Our results confirm and extend previous findings in men that OXT interacts with the brain reward system to reinforce partner value representations, indicating a common OXT-dependent mechanism underlying partner attraction in both sexes. This mechanism may be disturbed in women using HC, suggesting that gonadal steroids could alter partner-specific OXT effects. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

[Determination of irreversibility of clinical brain death. Electroencephalography and evoked potentials].

PubMed

Buchner, H; Ferbert, A

2016-02-01

Principally, in the fourth update of the rules for the procedure to finally determine the irreversible cessation of function of the cerebrum, the cerebellum and the brainstem, the importance of an electroencephalogram (EEG), somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) are confirmed. This paper presents the reliability and validity of the electrophysiological diagnosis, discusses the amendments in the fourth version of the guidelines and introduces the practical application, problems and sources of error.An EEG is the best established supplementary diagnostic method for determining the irreversibility of clinical brain death syndrome. It should be noted that residual brain activity can often persist for many hours after the onset of brain death syndrome, particularly in patients with primary brainstem lesions. The derivation and analysis of an EEG requires a high level of expertise to be able to safely distinguish artefacts from primary brain activity. The registration of EEGs to demonstrate the irreversibility of clinical brain death syndrome is extremely time consuming.The BAEPs can only be used to confirm the irreversibility of brain death syndrome in serial examinations or in the rare cases of a sustained wave I or sustained waves I and II. Very often, an investigation cannot be reliably performed because of existing sound conduction disturbances or failure of all potentials even before the onset of clinical brain death syndrome. This explains why BAEPs are only used in exceptional cases.The SEPs of the median nerve can be very reliably derived, are technically simple and with few sources of error. A serial investigation is not required and the time needed for examination is short. For these reasons SEPs are given preference over EEGs and BAEPs for establishing the irreversibility of clinical brain death syndrome.

The potential role of Morus alba leaves extract on the brain of mice infected with Schistosoma mansoni.

PubMed

Bauomy, Amira A

2014-01-01

Schistosomiasis is a neglected tropical disease which is associated with neuropsychiatric and neuropathological disorders. Herein, the main goal of the presented work is to investigate the effect of Morus alba leaves extract in mice brain infected with Schistosoma mansoni. Since, the resistance of Schistosomes to antischistosomal drug (praziquantel) has been examined, schistosomiasis induced brain oxidative stress as evidenced by the decrease of glutathione level, total antioxidant capacity and the activity of catalase significantly, while a significant elevation in the levels of nitrite/nitrate and malondialdhyde. In addition, the infection resulted in neurochemical disturbances, the main inhibitory amino acid, γ- aminobutyric acid level was decreased. In contrast, the level of chloride ions and acetylcholine esterase activity were significantly increased. Moreover, the histopathological section showed some impairments in the brain. The treatment with Morus alba leaves extract ameliorated the induced disturbances in schistosome-infected mice where the levels of non-enzymatic and enzymatic antioxidants were elevated. On the other hand, the levels of nitrite/nitrate and malondialdhyde were significantly reduced. Likewise, treatment of mice with Morus alba leaves extract improved the altered levels of γ- aminobutyric acid level and chloride ion. Also, it improved the recorded impairments of the histopathological section in the brain of schistosome infected mice.

Consistent, small effects of treefall disturbances on the composition and diversity of four Amazonian forests.

PubMed

Baker, Timothy R; Vela Díaz, Dilys M; Chama Moscoso, Victor; Navarro, Gilberto; Monteagudo, Abel; Pinto, Ruy; Cangani, Katia; Fyllas, Nikolaos M; Lopez Gonzalez, Gabriela; Laurance, William F; Lewis, Simon L; Lloyd, Jonathan; Ter Steege, Hans; Terborgh, John W; Phillips, Oliver L

2016-03-01

Understanding the resilience of moist tropical forests to treefall disturbance events is important for understanding the mechanisms that underlie species coexistence and for predicting the future composition of these ecosystems. Here, we test whether variation in the functional composition of Amazonian forests determines their resilience to disturbance.We studied the legacy of natural treefall disturbance events in four forests across Amazonia that differ substantially in functional composition. We compared the composition and diversity of all free-standing woody stems 2-10 cm diameter in previously disturbed and undisturbed 20 × 20 m subplots within 55, one-hectare, long-term forest inventory plots.Overall, stem number increased following disturbance, and species and functional composition shifted to favour light-wooded, small-seeded taxa. Alpha-diversity increased, but beta-diversity was unaffected by disturbance, in all four forests.Changes in response to disturbance in both functional composition and alpha-diversity were, however, small (2 - 4% depending on the parameter) and similar among forests. Synthesis . This study demonstrates that variation in the functional composition of Amazonian forests does not lead to large differences in the response of these forests to treefall disturbances, and overall, these events have a minor role in maintaining the diversity of these ecosystems.

Blood-Brain Barrier Alterations Provide Evidence of Subacute Diaschisis in an Ischemic Stroke Rat Model

PubMed Central

Garbuzova-Davis, Svitlana; Rodrigues, Maria C. O.; Hernandez-Ontiveros, Diana G.; Tajiri, Naoki; Frisina-Deyo, Aric; Boffeli, Sean M.; Abraham, Jerry V.; Pabon, Mibel; Wagner, Andrew; Ishikawa, Hiroto; Shinozuka, Kazutaka; Haller, Edward; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesario V.

2013-01-01

Background Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas. Methodology/Principal Findings In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO), significant BBB alterations characterized by large Evans Blue (EB) parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices. Conclusions/Significance These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke. PMID:23675488

Intrinsic network activity in tinnitus investigated using functional MRI

PubMed Central

Leaver, Amber M.; Turesky, Ted K.; Seydell-Greenwald, Anna; Morgan, Susan; Kim, Hung J.; Rauschecker, Josef P.

2016-01-01

Tinnitus is an increasingly common disorder in which patients experience phantom auditory sensations, usually ringing or buzzing in the ear. Tinnitus pathophysiology has been repeatedly shown to involve both auditory and non-auditory brain structures, making network-level studies of tinnitus critical. In this magnetic resonance imaging (MRI) study, we used two resting-state functional connectivity (RSFC) approaches to better understand functional network disturbances in tinnitus. First, we demonstrated tinnitus-related reductions in RSFC between specific brain regions and resting-state networks (RSNs), defined by independent components analysis (ICA) and chosen for their overlap with structures known to be affected in tinnitus. Then, we restricted ICA to data from tinnitus patients, and identified one RSN not apparent in control data. This tinnitus RSN included auditory-sensory regions like inferior colliculus and medial Heschl’s gyrus, as well as classically non-auditory regions like the mediodorsal nucleus of the thalamus, striatum, lateral prefrontal and orbitofrontal cortex. Notably, patients’ reported tinnitus loudness was positively correlated with RSFC between the mediodorsal nucleus and the tinnitus RSN, indicating that this network may underlie the auditory-sensory experience of tinnitus. These data support the idea that tinnitus involves network dysfunction, and further stress the importance of communication between auditory-sensory and fronto-striatal circuits in tinnitus pathophysiology. PMID:27091485

Clinical assessment of social cognitive function in neurological disorders.

PubMed

Henry, Julie D; von Hippel, William; Molenberghs, Pascal; Lee, Teresa; Sachdev, Perminder S

2016-01-01

Social cognition broadly refers to the processing of social information in the brain that underlies abilities such as the detection of others' emotions and responding appropriately to these emotions. Social cognitive skills are critical for successful communication and, consequently, mental health and wellbeing. Disturbances of social cognition are early and salient features of many neuropsychiatric, neurodevelopmental and neurodegenerative disorders, and often occur after acute brain injury. Its assessment in the clinic is, therefore, of paramount importance. Indeed, the most recent edition of the American Psychiatric Association's Diagnostic and Statistical Manual for Mental Disorders (DSM-5) introduced social cognition as one of six core components of neurocognitive function, alongside memory and executive control. Failures of social cognition most often present as poor theory of mind, reduced affective empathy, impaired social perception or abnormal social behaviour. Standard neuropsychological assessments lack the precision and sensitivity needed to adequately inform treatment of these failures. In this Review, we present appropriate methods of assessment for each of the four domains, using an example disorder to illustrate the value of these approaches. We discuss the clinical applications of testing for social cognitive function, and finally suggest a five-step algorithm for the evaluation and treatment of impairments, providing quantitative evidence to guide the selection of social cognitive measures in clinical practice.

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment.

PubMed

Peters, Sarah K; Dunlop, Katharine; Downar, Jonathan

2016-01-01

The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network's associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN's cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders.

Cortico-Striatal-Thalamic Loop Circuits of the Salience Network: A Central Pathway in Psychiatric Disease and Treatment

PubMed Central

Peters, Sarah K.; Dunlop, Katharine; Downar, Jonathan

2016-01-01

The salience network (SN) plays a central role in cognitive control by integrating sensory input to guide attention, attend to motivationally salient stimuli and recruit appropriate functional brain-behavior networks to modulate behavior. Mounting evidence suggests that disturbances in SN function underlie abnormalities in cognitive control and may be a common etiology underlying many psychiatric disorders. Such functional and anatomical abnormalities have been recently apparent in studies and meta-analyses of psychiatric illness using functional magnetic resonance imaging (fMRI) and voxel-based morphometry (VBM). Of particular importance, abnormal structure and function in major cortical nodes of the SN, the dorsal anterior cingulate cortex (dACC) and anterior insula (AI), have been observed as a common neurobiological substrate across a broad spectrum of psychiatric disorders. In addition to cortical nodes of the SN, the network’s associated subcortical structures, including the dorsal striatum, mediodorsal thalamus and dopaminergic brainstem nuclei, comprise a discrete regulatory loop circuit. The SN’s cortico-striato-thalamo-cortical loop increasingly appears to be central to mechanisms of cognitive control, as well as to a broad spectrum of psychiatric illnesses and their available treatments. Functional imbalances within the SN loop appear to impair cognitive control, and specifically may impair self-regulation of cognition, behavior and emotion, thereby leading to symptoms of psychiatric illness. Furthermore, treating such psychiatric illnesses using invasive or non-invasive brain stimulation techniques appears to modulate SN cortical-subcortical loop integrity, and these effects may be central to the therapeutic mechanisms of brain stimulation treatments in many psychiatric illnesses. Here, we review clinical and experimental evidence for abnormalities in SN cortico-striatal-thalamic loop circuits in major depression, substance use disorders (SUD), anxiety disorders, schizophrenia and eating disorders (ED). We also review emergent therapeutic evidence that novel invasive and non-invasive brain stimulation treatments may exert therapeutic effects by normalizing abnormalities in the SN loop, thereby restoring the capacity for cognitive control. Finally, we consider a series of promising directions for future investigations on the role of SN cortico-striatal-thalamic loop circuits in the pathophysiology and treatment of psychiatric disorders. PMID:28082874

Effect of bacoside A on membrane-bound ATPases in the brain of rats exposed to cigarette smoke.

PubMed

Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

2005-01-01

Membrane-bound enzymes play a vital role in neuronal function through maintenance of membrane potential and impulse propagation. We have evaluated the harmful effects of chronic cigarette smoking on membrane-bound ATPases and the protective effect of Bacoside A in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with Bacoside A (the active principle isolated from Bacopa monniera) at a dosage of 10 mg/kg b.w/day, p.o. The levels of lipid peroxides as marker for evaluating the extent of membrane damage, the activities of Na+/K+-ATPase, Ca2+-ATPase and Mg2+-ATPase, and associated cations sodium (Na+), potassium (K+), calcium (Ca2+), and magnesium (Mg2+) were investigated in the brain. Neuronal membrane damage was evident from the elevated levels of lipid peroxides and decreased activities of membrane-bound enzymes. Disturbances in the electrolyte balance with accumulation of Na+ and Ca2+ and depletion of K+ and Mg2+ were also observed. Administration of Bacoside A inhibited lipid peroxidation, improved the activities of ATPases, and maintained the ionic equilibrium. The results of our study indicate that Bacoside A protects the brain from cigarette smoking induced membrane damage. Copyright 2005 Wiley Periodicals, Inc.

Assessment of the dynamics of human glymphatic system by near-infrared spectroscopy.

PubMed

Myllylä, Teemu; Harju, Markus; Korhonen, Vesa; Bykov, Alexander; Kiviniemi, Vesa; Meglinski, Igor

2017-08-12

Fluctuations in brain water content has attracted increasing interest, particularly as regards studies of the glymphatic system, which is connected with the complex organization of dural lymphatic vessels, responsible for cleaning tissue. Disturbances of glymphatic circulation are associated with several brain disorders, including dementia. This article introduces an approach to noninvasive measurement of water dynamics in the human brain utilizing near-infrared spectroscopy (NIRS). We demonstrate the possibility to sense dynamic variations of water content between the skull and grey matter, for instance, in the subarachnoid space. Measured fluctuations in water content, especially in the cerebrospinal fluid (CSF), are assumed to be correlated with the dynamics of glymphatic circulation. The sampling volume for the NIRS optode was estimated by Monte Carlo modelling for the wavelengths of 660, 740, 830 and 980 nm. In addition, using combinations of these wavelengths, this article presents the calculation models for quantifying water and haemodynamics. The presented NIRS technique allows long-term functional brain monitoring, including sleeping time. Furthermore, it is used in combination with different magnetic neuroimaging techniques, particularly magnetic resonance encephalography. Using the combined setup, we report the preliminary results on the interaction between CSF and blood oxygen level-dependent fluctuations. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury

PubMed Central

Østergaard, Leif; Engedal, Thorbjørn S; Aamand, Rasmus; Mikkelsen, Ronni; Iversen, Nina K; Anzabi, Maryam; Næss-Schmidt, Erhard T; Drasbek, Kim R; Bay, Vibeke; Blicher, Jakob U; Tietze, Anna; Mikkelsen, Irene K; Hansen, Brian; Jespersen, Sune N; Juul, Niels; Sørensen, Jens CH; Rasmussen, Mads

2014-01-01

Most patients who die after traumatic brain injury (TBI) show evidence of ischemic brain damage. Nevertheless, it has proven difficult to demonstrate cerebral ischemia in TBI patients. After TBI, both global and localized changes in cerebral blood flow (CBF) are observed, depending on the extent of diffuse brain swelling and the size and location of contusions and hematoma. These changes vary considerably over time, with most TBI patients showing reduced CBF during the first 12 hours after injury, then hyperperfusion, and in some patients vasospasms before CBF eventually normalizes. This apparent neurovascular uncoupling has been ascribed to mitochondrial dysfunction, hindered oxygen diffusion into tissue, or microthrombosis. Capillary compression by astrocytic endfeet swelling is observed in biopsies acquired from TBI patients. In animal models, elevated intracranial pressure compresses capillaries, causing redistribution of capillary flows into patterns argued to cause functional shunting of oxygenated blood through the capillary bed. We used a biophysical model of oxygen transport in tissue to examine how capillary flow disturbances may contribute to the profound changes in CBF after TBI. The analysis suggests that elevated capillary transit time heterogeneity can cause critical reductions in oxygen availability in the absence of ‘classic' ischemia. We discuss diagnostic and therapeutic consequences of these predictions. PMID:25052556

Brain structural network topological alterations of the left prefrontal and limbic cortex in psychogenic erectile dysfunction.

PubMed

Chen, Jianhuai; Chen, Yun; Gao, Qingqiang; Chen, Guotao; Dai, Yutian; Yao, Zhijian; Lu, Qing

2018-05-01

Despite increasing understanding of the cerebral functional changes and structural abnormalities in erectile dysfunction, alterations in the topological organization of brain networks underlying psychogenic erectile dysfunction remain unclear. Here, based on the diffusion tensor image data of 25 patients and 26 healthy controls, we investigated the topological organization of brain structural networks and its correlations with the clinical variables using the graph theoretical analysis. Patients displayed a preserved overall small-world organization and exhibited a less connectivity strength in the left inferior frontal gyrus, amygdale and the right inferior temporal gyrus. Moreover, an abnormal hub pattern was observed in patients, which might disturb the information interactions of the remaining brain network. Additionally, the clustering coefficient of the left hippocampus was positively correlated with the duration of patients and the normalized betweenness centrality of the right anterior cingulate gyrus and the left calcarine fissure were negatively correlated with the sum scores of the 17-item Hamilton Depression Rating Scale. These findings suggested that the damaged white matter and the abnormal hub distribution of the left prefrontal and limbic cortex might contribute to the pathogenesis of psychogenic erectile dysfunction and provided new insights into the understanding of the pathophysiological mechanisms of psychogenic erectile dysfunction.

Sleep Disturbance, Daytime Symptoms, and Functional Performance in Patients With Stable Heart Failure: A Mediation Analysis.

PubMed

Jeon, Sangchoon; Redeker, Nancy S

2016-01-01

Sleep disturbance is common among patients with heart failure (HF) who also experience symptom burden and poor functional performance. We evaluated the extent to which sleep-related, daytime symptoms (fatigue, excessive daytime sleepiness, and depressive symptoms) mediate the relationship between sleep disturbance and functional performance among patients with stable HF. We recruited patients with stable HF for this secondary analysis of data from a cross-sectional, observational study. Participants completed unattended ambulatory polysomnography from which the Respiratory Disturbance Index was calculated, along with a Six-Minute Walk Test, questionnaires to elicit sleep disturbance (Pittsburgh Sleep Quality Index, Insomnia Symptoms from the Sleep Habits Questionnaire), daytime symptoms (Center for Epidemiologic Studies Depression Scale, Global Fatigue Index, Epworth Sleepiness Scale), and self-reported functional performance (Medical Outcomes Study SF36 V2 Physical Function Scale). We used structural equation modeling with latent variables for the key analysis. Follow-up, exploratory regression analysis with bootstrapped samples was used to examine the extent to which individual daytime symptoms mediated effects of sleep disturbance on functional performance after controlling for clinical and demographic covariates. The sample included 173 New York Heart Association Class I-IV HF patients (n = 60/34.7% women; M = 60.7, SD = 16.07 years of age). Daytime symptoms mediated the relationship between sleep disturbance and functional performance. Fatigue and depression mediated the relationship between insomnia symptoms and self-reported functional performance, whereas fatigue and sleepiness mediated the relationship between sleep quality and functional performance. Sleepiness mediated the relationship between the respiratory index and self-reported functional performance only in people who did not report insomnia. Daytime symptoms explain the relationships between sleep disturbance and functional performance in stable HF.

Interhemispheric Functional Brain Connectivity in Neonates with Prenatal Alcohol Exposure: Preliminary Findings.

PubMed

Donald, Kirsten A; Ipser, Jonathan C; Howells, Fleur M; Roos, Annerine; Fouche, Jean-Paul; Riley, Edward P; Koen, Nastassja; Woods, Roger P; Biswal, Bharat; Zar, Heather J; Narr, Katherine L; Stein, Dan J

2016-01-01

Children exposed to alcohol in utero demonstrate reduced white matter microstructural integrity. While early evidence suggests altered functional brain connectivity in the lateralization of motor networks in school-age children with prenatal alcohol exposure (PAE), the specific effects of alcohol exposure on the establishment of intrinsic connectivity in early infancy have not been explored. Sixty subjects received functional imaging at 2 to 4 weeks of age for 6 to 8 minutes during quiet natural sleep. Thirteen alcohol-exposed (PAE) and 14 age-matched control (CTRL) participants with usable data were included in a multivariate model of connectivity between sensorimotor intrinsic functional connectivity networks. Seed-based analyses of group differences in interhemispheric connectivity of intrinsic motor networks were also conducted. The Dubowitz neurological assessment was performed at the imaging visit. Alcohol exposure was associated with significant increases in connectivity between somatosensory, motor networks, brainstem/thalamic, and striatal intrinsic networks. Reductions in interhemispheric connectivity of motor and somatosensory networks did not reach significance. Although results are preliminary, findings suggest PAE may disrupt the temporal coherence in blood oxygenation utilization in intrinsic networks underlying motor performance in newborn infants. Studies that employ longitudinal designs to investigate the effects of in utero alcohol exposure on the evolving resting-state networks will be key in establishing the distribution and timing of connectivity disturbances already described in older children. Copyright © 2016 by the Research Society on Alcoholism.

Resting-State Functional Connectivity in Patients with Long-Term Remission of Cushing's Disease

PubMed Central

van der Werff, Steven J A; Pannekoek, J Nienke; Andela, Cornelie D; Meijer, Onno C; van Buchem, Mark A; Rombouts, Serge A R B; van der Mast, Roos C; Biermasz, Nienke R; Pereira, Alberto M; van der Wee, Nic J A

2015-01-01

Glucocorticoid disturbance can be a cause of psychiatric symptoms. Cushing's disease represents a unique model for examining the effects of prolonged exposure to high levels of endogenous cortisol on the human brain as well as for examining the relation between these effects and psychiatric symptomatology. This study aimed to investigate resting-state functional connectivity (RSFC) of the limbic network, the default mode network (DMN), and the executive control network in patients with long-term remission of Cushing's disease. RSFC of these three networks of interest was compared between patients in remission of Cushing's disease (n=24; 4 male, mean age=44.96 years) and matched healthy controls (n=24; 4 male, mean age=46.5 years), using probabilistic independent component analysis to extract the networks and a dual regression method to compare both groups. Psychological and cognitive functioning was assessed with validated questionnaires and interviews. In comparison with controls, patients with remission of Cushing's disease showed an increased RSFC between the limbic network and the subgenual subregion of the anterior cingulate cortex (ACC) as well as an increased RSFC of the DMN in the left lateral occipital cortex. However, these findings were not associated with psychiatric symptoms in the patient group. Our data indicate that previous exposure to hypercortisolism is related to persisting changes in brain function. PMID:25652248

Thiothixene

MedlinePlus

... disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions). Thiothixene is in a group of medications called conventional antipsychotics. It works by decreasing abnormal excitement in the brain.

Loxapine

MedlinePlus

... disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions). Loxapine is in a group of medications called conventional antipsychotics. It works by decreasing abnormal excitement in the brain.

Brain functional connectivity and the pathophysiology of schizophrenia.

PubMed

Angelopoulos, E

2014-01-01

In the last decade there is extensive evidence to suggest that cognitive functions depending on coordination of distributed neuronal responses are associated with synchronized oscillatory activity in various frequency ranges suggesting a functional mechanism of neural oscillations in cortical networks. In addition to their role in normal brain functioning, there is increasing evidence that altered oscillatory activity may be associated with certain neuropsychiatric disorders, such as schizophrenia. Consequently, disturbances in neural synchronization may represent the functional relationship of disordered connectivity of cortical networks underlying the characteristic fragmentation of mind and behavior in schizophrenia. In recent studies the synchronization of oscillatory activity in the experience of characteristic symptoms such as auditory verbal hallucinations and thought blocks have been studied in patients with schizophrenia. Studies involving analysis of EEG activity obtained from individuals in resting state (in cage Faraday, isolated from external influences and with eyes closed). In patients with schizophrenia and persistent auditory verbal hallucinations (AVHs) observed a temporary increase in the synchronization phase of α and high θ oscillations of the electroencephalogram (EEG) compared with those of healthy controls and patients without AVHs . This functional hyper-connection manifested in time windows corresponding to experience AVHs, as noted by the patients during the recording of EEG and observed in speech related cortical areas. In another study an interaction of theta and gamma oscillations engages in the production and experience of AVHs. The results showed increased phase coupling between theta and gamma EEG rhythms in the left temporal cortex during AVHs experiences. A more recent study, approaches the thought blocking experience in terms of functional brain connectivity. Thought blocks (TBs) are characterized by regular interruptions of the flow of thought. Outward signs are abrupt and repeated interruptions in the flow of conversation or actions while subjective experience is that of a total and uncontrollable emptying of the mind. In the very limited bibliography regarding TB, the phenomenon is thought to be conceptualized as a disturbance of consciousness that can be attributed to stoppages of continuous information processing due to an increase in the volume of information to be processed. In an attempt to investigate potential expression of the phenomenon on the functional properties of electroencephalographic (EEG) activity, an EEG study was contacted in schizophrenic patients with persisting auditory verbal hallucinations (AVHs) who additionally exhibited TBs. Phase synchronization analyses performed on EEG segments during the experience of TBs showed that synchrony values exhibited a long-range common mode of coupling (grouped behavior) among the left temporal area and the remaining central and frontal brain areas. These common synchrony-fluctuation schemes were observed for 0.5 to 2 s and were detected in a 4-s window following the estimated initiation of the phenomenon. The observation was frequency specific and detected in the broad alpha band region (6-12 Hz). The introduction of synchrony entropy (SE) analysis applied on the cumulative synchrony distribution showed that TB states were characterized by an explicit preference of the system to be functioned at low values of synchrony, while the synchrony values are broadly distributed during the recovery state. The results indicate that during TB states, the phase locking of several brain areas were converged uniformly in a narrow band of low synchrony values and in a distinct time window, impeding thus the ability of the system to recruit and to process information during this time window. The results of this study seem to have greater importance on neuronal correlation of consciousness. The brain is a highly distributed system in which numerous operations are executed in parallel and that lacks a single coordinating center. This raises the question of how the computations occurring simultaneously in spatially segregated processing areas are coordinated and bound together to give rise to coherent percepts and actions. One of the coordinating mechanisms appears to be the synchronization of neuronal activity by phase locking of self-generated network oscillations. This led to the hypothesis that the cerebral cortex might exploit the option to synchronize the discharges of neurons with millisecond ` theoretical formulations of the binding-by-synchrony hypothesis were proposed earlier by Milner (1974), but the Singer lab in the 1990s was the first to obtain experimental evidence supporting the potential role of synchrony as a relational code. The results concerning the functional connectivity of the brain during TBs further support the hypothesis of phase synchronization as a key mechanism for neuronal assemblies underlying mental representations in the human brain.

Disturbed functional connectivity of cortical activation during semantic discrimination in patients with schizophrenia and subjects at genetic high-risk.

PubMed

Li, Xiaobo; Branch, Craig A; Nierenberg, Jay; Delisi, Lynn E

2010-03-01

Schizophrenia has a strong genetic component that is relevant to the understanding of the pathophysiology of the syndrome. Thus, recent investigations have shifted from studies of diagnosed patients with schizophrenia to examining their unaffected relatives. Previous studies found that during language processing, relatives thought to be at genetic high-risk for the disorder exhibit aberrant functional activation in regions of language processing, specifically in the left inferior frontal gyrus (Broca's area). However, functional connectivity among the regions involved in language pathways is not well understood. In this study, we examined the functional connectivity between a seed located in Broca's area and the remainder of the brain during a visual lexical decision task, in 20 schizophrenia patients, 21 subjects at genetic high risk for the disorder and 21 healthy controls. Both the high-risk subjects and patients showed significantly reduced activation correlations between seed and regions related to visual language processing. Compared to the high-risk subjects, the schizophrenia patients showed even fewer regions that were correlated with the seed regions. These results suggest that there is aberrant functional connectivity within cortical language circuitry in high-risk subjects and patients with schizophrenia. Broca's area, which is one of the important regions for language processing in healthy controls, had a significantly reduced role in the high-risk subjects and patients with schizophrenia. Our findings are consistent with the existence of an underlying biological disturbance that begins in genetically at risk individuals and progresses to a greater extent in those who eventually develop schizophrenia.

Longitudinal functional connectivity changes correlate with mood improvement after regular exercise in a dose-dependent fashion.

PubMed

Tozzi, Leonardo; Carballedo, Angela; Lavelle, Grace; Doolin, Kelly; Doyle, Myles; Amico, Francesco; McCarthy, Hazel; Gormley, John; Lord, Anton; O'Keane, Veronica; Frodl, Thomas

2016-04-01

Exercise increases wellbeing and improves mood. It is however unclear how these mood changes relate to brain function. We conducted a randomized controlled trial investigating resting-state modifications in healthy adults after an extended period of aerobic physical exercise and their relationship with mood improvements. We aimed to identify novel functional networks whose activity could provide a physiological counterpart to the mood-related benefits of exercise. Thirty-eight healthy sedentary volunteers were randomised to either the aerobic exercise group of the study or a control group. Participants in the exercise group attended aerobic sessions with a physiotherapist twice a week for 16 weeks. Resting-state modifications using magnetic resonance imaging were assessed before and after the programme and related to mood changes. An unbiased approach using graph metrics and network-based statistics was adopted. Exercise reduced mood disturbance and improved emotional wellbeing. It also induced a decrease in local efficiency in the parahippocampal lobe through strengthening of the functional connections from this structure to the supramarginal gyrus, precentral area, superior temporal gyrus and temporal pole. Changes in mood disturbance following exercise were correlated with those in connectivity between parahippocampal gyrus and superior temporal gyrus as well as with the amount of training. No changes were detected in the control group. In conclusion, connectivity from the parahippocampal gyrus to motor, sensory integration and mood regulation areas was strengthened through exercise. These functional changes might be related to the benefits of regular physical activity on mood. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Experimental gastritis leads to anxiety- and depression-like behaviors in female but not male rats

PubMed Central

2013-01-01

Human and animals studies support the idea that there is a gender-related co-morbidity of pain-related and inflammatory gastrointestinal (GI) diseases with psychological disorders. This co-morbidity is the evidence for the existence of GI-brain axis which consists of immune (cytokines), neural (vagus nerve) and neuroendocrine (HPA axis) pathways. Psychological stress causes disturbances in GI physiology, such as altered GI barrier function, changes in motility and secretion, development of visceral hypersensitivity, and dysfunction of inflammatory responses. Whether GI inflammation would exert impact on psychological behavior is not well established. We examined the effect of experimental gastritis on anxiety- and depression-like behaviors in male and female Sprague–Dawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7 days. Sucrose preference test assessed the depression-like behavior, open field test and elevated plus maze evaluated the anxiety-like behavior. IAA treatment induced gastric inflammation in rats of either gender. No behavioral abnormality or dysfunction of GI-brain axis was observed in male rats with IAA-induced gastritis. Anxiety- and depression-like behaviors were apparent and the HPA axis was hyperactive in female rats with IAA-induced gastritis. Our results show that gastric inflammation leads to anxiety- and depression-like behaviors in female but not male rats via the neuroendocrine (HPA axis) pathway, suggesting that the GI inflammation can impair normal brain function and induce changes in psychological behavior in a gender-related manner through the GI-to-brain signaling. PMID:24345032

Neurochemical profile of dementia pugilistica.

PubMed

Kokjohn, Tyler A; Maarouf, Chera L; Daugs, Ian D; Hunter, Jesse M; Whiteside, Charisse M; Malek-Ahmadi, Michael; Rodriguez, Emma; Kalback, Walter; Jacobson, Sandra A; Sabbagh, Marwan N; Beach, Thomas G; Roher, Alex E

2013-06-01

Dementia pugilistica (DP), a suite of neuropathological and cognitive function declines after chronic traumatic brain injury (TBI), is present in approximately 20% of retired boxers. Epidemiological studies indicate TBI is a risk factor for neurodegenerative disorders including Alzheimer disease (AD) and Parkinson disease (PD). Some biochemical alterations observed in AD and PD may be recapitulated in DP and other TBI persons. In this report, we investigate long-term biochemical changes in the brains of former boxers with neuropathologically confirmed DP. Our experiments revealed biochemical and cellular alterations in DP that are complementary to and extend information already provided by histological methods. ELISA and one-dimensional and two dimensional Western blot techniques revealed differential expression of select molecules between three patients with DP and three age-matched non-demented control (NDC) persons without a history of TBI. Structural changes such as disturbances in the expression and processing of glial fibrillary acidic protein, tau, and α-synuclein were evident. The levels of the Aβ-degrading enzyme neprilysin were reduced in the patients with DP. Amyloid-β levels were elevated in the DP participant with the concomitant diagnosis of AD. In addition, the levels of brain-derived neurotrophic factor and the axonal transport proteins kinesin and dynein were substantially decreased in DP relative to NDC participants. Traumatic brain injury is a risk factor for dementia development, and our findings are consistent with permanent structural and functional damage in the cerebral cortex and white matter of boxers. Understanding the precise threshold of damage needed for the induction of pathology in DP and TBI is vital.

Neurochemical Profile of Dementia Pugilistica

PubMed Central

Kokjohn, Tyler A.; Maarouf, Chera L.; Daugs, Ian D.; Hunter, Jesse M.; Whiteside, Charisse M.; Malek-Ahmadi, Michael; Rodriguez, Emma; Kalback, Walter; Jacobson, Sandra A.; Sabbagh, Marwan N.; Beach, Thomas G.

2013-01-01

Abstract Dementia pugilistica (DP), a suite of neuropathological and cognitive function declines after chronic traumatic brain injury (TBI), is present in approximately 20% of retired boxers. Epidemiological studies indicate TBI is a risk factor for neurodegenerative disorders including Alzheimer disease (AD) and Parkinson disease (PD). Some biochemical alterations observed in AD and PD may be recapitulated in DP and other TBI persons. In this report, we investigate long-term biochemical changes in the brains of former boxers with neuropathologically confirmed DP. Our experiments revealed biochemical and cellular alterations in DP that are complementary to and extend information already provided by histological methods. ELISA and one-dimensional and two dimensional Western blot techniques revealed differential expression of select molecules between three patients with DP and three age-matched non-demented control (NDC) persons without a history of TBI. Structural changes such as disturbances in the expression and processing of glial fibrillary acidic protein, tau, and α-synuclein were evident. The levels of the Aβ–degrading enzyme neprilysin were reduced in the patients with DP. Amyloid-β levels were elevated in the DP participant with the concomitant diagnosis of AD. In addition, the levels of brain-derived neurotrophic factor and the axonal transport proteins kinesin and dynein were substantially decreased in DP relative to NDC participants. Traumatic brain injury is a risk factor for dementia development, and our findings are consistent with permanent structural and functional damage in the cerebral cortex and white matter of boxers. Understanding the precise threshold of damage needed for the induction of pathology in DP and TBI is vital. PMID:23268705

Lipid rafts regulate PCB153-induced disruption of occludin and brain endothelial barrier function through protein phosphatase 2A and matrix metalloproteinase-2

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

Eum, Sung Yong, E-mail: seum@miami.edu; Jaraki, Dima; András, Ibolya E.

Occludin is an essential integral transmembrane protein regulating tight junction (TJ) integrity in brain endothelial cells. Phosphorylation of occludin is associated with its localization to TJ sites and incorporation into intact TJ assembly. The present study is focused on the role of lipid rafts in polychlorinated biphenyl (PCB)-induced disruption of occludin and endothelial barrier function. Exposure of human brain endothelial cells to 2,2′,4,4′,5,5′-hexachlorobiphenyl (PCB153) induced dephosphorylation of threonine residues of occludin and displacement of occludin from detergent-resistant membrane (DRM)/lipid raft fractions within 1 h. Moreover, lipid rafts modulated the reduction of occludin level through activation of matrix metalloproteinase 2 (MMP-2)more » after 24 h PCB153 treatment. Inhibition of protein phosphatase 2A (PP2A) activity by okadaic acid or fostriecin markedly protected against PCB153-induced displacement of occludin and increased permeability of endothelial cells. The implication of lipid rafts and PP2A signaling in these processes was further defined by co-immunoprecipitation of occludin with PP2A and caveolin-1, a marker protein of lipid rafts. Indeed, a significant MMP-2 activity was observed in lipid rafts and was increased by exposure to PCB153. The pretreatment of MMP-2 inhibitors protected against PCB153-induced loss of occludin and disruption of lipid raft structure prevented the increase of endothelial permeability. Overall, these results indicate that lipid raft-associated processes, such as PP2A and MMP-2 activation, participate in PCB153-induced disruption of occludin function in brain endothelial barrier. This study contributes to a better understanding of the mechanisms leading to brain endothelial barrier dysfunction in response to exposure to environmental pollutants, such as ortho-substituted PCBs. - Highlights: • PCB153 disturbed human brain endothelial barrier through disruption of occludin. • Lipid raft-associated PP2A/MMP-2 induced PCB153-induced dysfunction of occludin. • Disrupted lipid rafts modulated PCB153-induced increase of permeability. • Lipid rafts act as a signaling platform for PCB153-induced dysfunction of occludin.« less

Basal Ganglia Circuits as Targets for Neuromodulation in Parkinson Disease.

PubMed

DeLong, Mahlon R; Wichmann, Thomas

2015-11-01

The revival of stereotactic surgery for Parkinson disease (PD) in the 1990s, with pallidotomy and then with high-frequency deep brain stimulation (DBS), has led to a renaissance in functional surgery for movement and other neuropsychiatric disorders. To examine the scientific foundations and rationale for the use of ablation and DBS for treatment of neurologic and psychiatric diseases, using PD as the primary example. A summary of the large body of relevant literature is presented on anatomy, physiology, pathophysiology, and functional surgery for PD and other basal ganglia disorders. The signs and symptoms of movement disorders appear to result largely from signature abnormalities in one of several parallel and largely segregated basal ganglia thalamocortical circuits (ie, the motor circuit). The available evidence suggests that the varied movement disorders resulting from dysfunction of this circuit result from propagated disruption of downstream network activity in the thalamus, cortex, and brainstem. Ablation and DBS act to free downstream networks to function more normally. The basal ganglia thalamocortical circuit may play a key role in the expression of disordered movement, and the basal ganglia-brainstem projections may play roles in akinesia and disturbances of gait. Efforts are under way to target circuit dysfunction in brain areas outside of the traditionally implicated basal ganglia thalamocortical system, in particular, the pedunculopontine nucleus, to address gait disorders that respond poorly to levodopa and conventional DBS targets. Deep brain stimulation is now the treatment of choice for many patients with advanced PD and other movement disorders. The success of DBS and other forms of neuromodulation for neuropsychiatric disorders is the result of the ability to modulate circuit activity in discrete functional domains within the basal ganglia circuitry with highly focused interventions, which spare uninvolved areas that are often disrupted with drugs.

Altered resting-state hippocampal and caudate functional networks in patients with obstructive sleep apnea.

PubMed

Song, Xiaopeng; Roy, Bhaswati; Kang, Daniel W; Aysola, Ravi S; Macey, Paul M; Woo, Mary A; Yan-Go, Frisca L; Harper, Ronald M; Kumar, Rajesh

2018-05-10

Brain structural injury and metabolic deficits in the hippocampus and caudate nuclei may contribute to cognitive and emotional deficits found in obstructive sleep apnea (OSA) patients. If such contributions exist, resting-state interactions of these subcortical sites with cortical areas mediating affective symptoms and cognition should be disturbed. Our aim was to examine resting-state functional connectivity (FC) of the hippocampus and caudate to other brain areas in OSA relative to control subjects, and to relate these changes to mood and neuropsychological scores. We acquired resting-state functional magnetic resonance imaging (fMRI) data from 70 OSA and 89 healthy controls using a 3.0-Tesla magnetic resonance imaging scanner, and assessed psychological and behavioral functions, as well as sleep issues. After standard fMRI data preprocessing, FC maps were generated for bilateral hippocampi and caudate nuclei, and compared between groups (ANCOVA; covariates, age and gender). Obstructive sleep apnea subjects showed significantly higher levels of anxiety and depressive symptoms over healthy controls. In OSA subjects, the hippocampus showed disrupted FC with the thalamus, para-hippocampal gyrus, medial and superior temporal gyrus, insula, and posterior cingulate cortex. Left and right caudate nuclei showed impaired FC with the bilateral inferior frontal gyrus and right angular gyrus. In addition, altered limbic-striatal-cortical FC in OSA showed relationships with behavioral and neuropsychological variables. The compromised hippocampal-cortical FC in OSA may underlie depression and anxious mood levels in OSA, while impaired caudate-cortical FC may indicate deficits in reward processing and cognition. These findings provide insights into the neural mechanisms underlying the comorbidity of mood and cognitive deficits in OSA. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Splenectomy Fails to Provide Long-Term Protection Against Ischemic Stroke.

PubMed

Ran, Yuanyuan; Liu, Zongjian; Huang, Shuo; Shen, Jiamei; Li, Fengwu; Zhang, Wenxiu; Chen, Chen; Geng, Xiaokun; Ji, Zhili; Du, Huishan; Hu, Xiaoming

2018-06-01

Splenectomy before or immediately after stroke provides early brain protection. This study aims to explore the effect of splenectomy on long-term neurological recovery after stroke, which is currently lacking in the field. Adult male rats were randomized into splenectomy or sham groups and then subjected to 90 min of middle cerebral artery occlusion (MCAO). Spleen was removed right upon reperfusion or 3d after MCAO. Infarct volume, neurological functions, and peripheral immune cell populations were assessed up to 28d after stroke. The results show that delayed removal of spleen did not reduce brain tissue loss and showed no effect on sensorimotor function (Rotarod, beam balance, forelimb placing, grid walk, and adhesive removal tests) or cognitive function (Morris water maze). Spleen removal immediately upon reperfusion, although significantly reduced the infarct size and immune cell infiltration 3d after MCAO, also failed to promote long-term recovery. Flow cytometry analysis demonstrated that immediate splenectomy after MCAO resulted in a prolonged decrease in the percentage of CD3 + CD4 + and CD3 + CD8 + T cells in total lymphocytes as compared to non-splenectomy MCAO rats. In contrast, the percentage of CD3 - CD45RA + B cells was significantly elevated after splenectomy. As a result, the ratio of T/B cells was significantly reduced in stroke rats with splenectomy. In conclusion, delayed splenectomy failed to provide long-term protection to the ischemic brain or improve functional recovery. The acute neuroprotective effect achieved by early splenectomy after stroke cannot last for long term. This loss of neuroprotection might be related to the prolonged disturbance in the T cell to B cell ratio.

Molindone

MedlinePlus

... disturbed or unusual thinking, loss of interest in life, and strong or inappropriate emotions). Molindone is in a class of medications called conventional (typical) antipsychotics. It works by decreasing abnormal excitement in the brain.

Cerebral Perfusion Is Perturbed by Preterm Birth and Brain Injury.

PubMed

Mahdi, E S; Bouyssi-Kobar, M; Jacobs, M B; Murnick, J; Chang, T; Limperopoulos, C

2018-05-10

Early disturbances in systemic and cerebral hemodynamics are thought to mediate prematurity-related brain injury. However, the extent to which CBF is perturbed by preterm birth is unknown. Our aim was to compare global and regional CBF in preterm infants with and without brain injury on conventional MR imaging using arterial spin-labeling during the third trimester of ex utero life and to examine the relationship between clinical risk factors and CBF. We prospectively enrolled preterm infants younger than 32 weeks' gestational age and <1500 g and performed arterial spin-labeling MR imaging studies. Global and regional CBF in the cerebral cortex, thalami, pons, and cerebellum was quantified. Preterm infants were stratified into those with and without structural brain injury. We further categorized preterm infants by brain injury severity: moderate-severe and mild. We studied 78 preterm infants: 31 without brain injury and 47 with brain injury (29 with mild and 18 with moderate-severe injury). Global CBF showed a borderline significant increase with increasing gestational age at birth ( P = .05) and trended lower in preterm infants with brain injury ( P = .07). Similarly, regional CBF was significantly lower in the right thalamus and midpons ( P < .05) and trended lower in the midtemporal, left thalamus, and anterior vermis regions ( P < .1) in preterm infants with brain injury. Regional CBF in preterm infants with moderate-severe brain injury trended lower in the midpons, right cerebellar hemisphere, and dentate nuclei compared with mild brain injury ( P < .1). In addition, a significant, lower regional CBF was associated with ventilation, sepsis, and cesarean delivery ( P < .05). We report early disturbances in global and regional CBF in preterm infants following brain injury. Regional cerebral perfusion alterations were evident in the thalamus and pons, suggesting regional vulnerability of the developing cerebro-cerebellar circuitry. © 2018 by American Journal of Neuroradiology.

Therapeutic brain modulation with targeted large neutral amino acid supplements in the Pah-enu2 phenylketonuria mouse model.

PubMed

van Vliet, Danique; Bruinenberg, Vibeke M; Mazzola, Priscila N; van Faassen, Martijn Hjr; de Blaauw, Pim; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Kema, Ido P; Heiner-Fokkema, M Rebecca; van der Zee, Eddy A; van Spronsen, Francjan J

2016-11-01

Phenylketonuria treatment consists mainly of a Phe-restricted diet, which leads to suboptimal neurocognitive and psychosocial outcomes. Supplementation of large neutral amino acids (LNAAs) has been suggested as an alternative dietary treatment strategy to optimize neurocognitive outcome in phenylketonuria and has been shown to influence 3 brain pathobiochemical mechanisms in phenylketonuria, but its optimal composition has not been established. In order to provide additional pathobiochemical insight and develop optimal LNAA treatment, several targeted LNAA supplements were investigated with respect to all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria. Pah-enu2 (PKU) mice received 1 of 5 different LNAA-supplemented diets beginning at postnatal day 45. Control groups included phenylketonuria mice receiving an isonitrogenic and isocaloric high-protein diet or the AIN-93M diet, and wild-type mice receiving the AIN-93M diet. After 6 wk, brain and plasma amino acid profiles and brain monoaminergic neurotransmitter concentrations were measured. Brain Phe concentrations were most effectively reduced by supplementation of LNAAs, such as Leu and Ile, with a strong affinity for the LNAA transporter type 1. Brain non-Phe LNAAs could be restored on supplementation, but unbalanced LNAA supplementation further reduced brain concentrations of those LNAAs that were not (sufficiently) included in the LNAA supplement. To optimally ameliorate brain monoaminergic neurotransmitter concentrations, LNAA supplementation should include Tyr and Trp together with LNAAs that effectively reduce brain Phe concentrations. The requirement for Tyr supplementation is higher than it is for Trp, and the relative effect of brain Phe reduction is higher for serotonin than it is for dopamine and norepinephrine. The study shows that all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria can be targeted by specific LNAA supplements. The study thus provides essential information for the development of optimal LNAA supplementation as an alternative dietary treatment strategy to optimize neurocognitive outcome in patients with phenylketonuria. © 2016 American Society for Nutrition.

Effects of hypoglycaemia on neuronal metabolism in the adult brain: role of alternative substrates to glucose.

PubMed

Amaral, Ana I

2013-07-01

Hypoglycaemia is characterized by decreased blood glucose levels and is associated with different pathologies (e.g. diabetes, inborn errors of metabolism). Depending on its severity, it might affect cognitive functions, including impaired judgment and decreased memory capacity, which have been linked to alterations of brain energy metabolism. Glucose is the major cerebral energy substrate in the adult brain and supports the complex metabolic interactions between neurons and astrocytes, which are essential for synaptic activity. Therefore, hypoglycaemia disturbs cerebral metabolism and, consequently, neuronal function. Despite the high vulnerability of neurons to hypoglycaemia, important neurochemical changes enabling these cells to prolong their resistance to hypoglycaemia have been described. This review aims at providing an overview over the main metabolic effects of hypoglycaemia on neurons, covering in vitro and in vivo findings. Recent studies provided evidence that non-glucose substrates including pyruvate, glycogen, ketone bodies, glutamate, glutamine, and aspartate, are metabolized by neurons in the absence of glucose and contribute to prolong neuronal function and delay ATP depletion during hypoglycaemia. One of the pathways likely implicated in the process is the pyruvate recycling pathway, which allows for the full oxidation of glutamate and glutamine. The operation of this pathway in neurons, particularly after hypoglycaemia, has been re-confirmed recently using metabolic modelling tools (i.e. Metabolic Flux Analysis), which allow for a detailed investigation of cellular metabolism in cultured cells. Overall, the knowledge summarized herein might be used for the development of potential therapies targeting neuronal protection in patients vulnerable to hypoglycaemic episodes.

Uncovering the role of the insula in non-motor symptoms of Parkinson's disease.

PubMed

Christopher, Leigh; Koshimori, Yuko; Lang, Anthony E; Criaud, Marion; Strafella, Antonio P

2014-08-01

Patients with Parkinson's disease experience a range of non-motor symptoms, including cognitive impairment, behavioural changes, somatosensory and autonomic disturbances. The insula, which was once thought to be primarily a limbic cortical structure, is now known to be highly involved in integrating somatosensory, autonomic and cognitive-affective information to guide behaviour. Thus, it acts as a central hub for processing relevant information related to the state of the body as well as cognitive and mood states. Despite these crucial functions, the insula has been largely overlooked as a potential key region in contributing to non-motor symptoms of Parkinson's disease. The insula is affected in Parkinson's disease by alpha-synuclein deposition, disruptions in normal neurotransmitter function, alterations in connectivity as well as metabolic and structural changes. Although research focusing on the role of the insula in Parkinson's disease is scarce, there is evidence from neuroimaging studies linking the insula to cognitive decline, behavioural abnormalities and somatosensory disturbances. Here, we review imaging studies that provide insight into the potential role of the insula in Parkinson's disease non-motor symptoms. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Behavior and the cholinergic parameters in olfactory bulbectomized female rodents: Difference between rats and mice.

PubMed

Stepanichev, Mikhail; Markov, Daniil; Pasikova, Natalia; Gulyaeva, Natalia

2016-01-15

Olfactory bulbectomy (OBX) in rodents induces a wide spectrum of functional disturbances, including behavioral, neurochemical, and neuromorphological alterations. We have examined the effects of OBX on behavior and the parameters of the cholinergic system in female rats and mice. In rats, OBX resulted in the appearance of some depressive-like behavioral marks, such as the decreased sucrose consumption, hyperactivity, impaired short-term memory and anxiety-like behavioral features, such as shortened presence in the center of the open field arena or open arms of the elevated plus-maze and an enhancement of avoidance behavior. These behavioral abnormalities could be associated with disturbances in hippocampal function, this suggestion being supported by the presence of cellular changes in this brain structure. No effect of OBX on the number of cholinergic neurons in the medial septum-diagonal band as well as on the acetylcholine content and acetylcholinesterase activity in the septum, hippocampus, and neocortex could be detected. In contrast, in mice, OBX impaired spontaneous alternation behavior and decreased the number of cholinergic neurons in the medial septum-diagonal band. These data demonstrate that rats and mice differently respond to OBX, in particular, OBX does not significantly affect the cholinergic system in rats. Copyright © 2015 Elsevier B.V. All rights reserved.

Disturbance of visual search by stimulating to posterior parietal cortex in the brain using transcranial magnetic stimulation

NASA Astrophysics Data System (ADS)

Iramina, Keiji; Ge, Sheng; Hyodo, Akira; Hayami, Takehito; Ueno, Shoogo

2009-04-01

In this study, we applied a transcranial magnetic stimulation (TMS) to investigate the temporal aspect for the functional processing of visual attention. Although it has been known that right posterior parietal cortex (PPC) in the brain has a role in certain visual search tasks, there is little knowledge about the temporal aspect of this area. Three visual search tasks that have different difficulties of task execution individually were carried out. These three visual search tasks are the "easy feature task," the "hard feature task," and the "conjunction task." To investigate the temporal aspect of the PPC involved in the visual search, we applied various stimulus onset asynchronies (SOAs) and measured the reaction time of the visual search. The magnetic stimulation was applied on the right PPC or the left PPC by the figure-eight coil. The results show that the reaction times of the hard feature task are longer than those of the easy feature task. When SOA=150 ms, compared with no-TMS condition, there was a significant increase in target-present reaction time when TMS pulses were applied. We considered that the right PPC was involved in the visual search at about SOA=150 ms after visual stimulus presentation. The magnetic stimulation to the right PPC disturbed the processing of the visual search. However, the magnetic stimulation to the left PPC gives no effect on the processing of the visual search.

Pretreatment with minocycline restores neurogenesis in the subventricular zone and subgranular zone of the hippocampus after ketamine exposure in neonatal rats.

PubMed

Lu, Yang; Giri, P K; Lei, Shan; Zheng, Juan; Li, Weisong; Wang, Ning; Chen, Xinlin; Lu, Haixia; Zuo, Zhiyi; Liu, Yong; Zhang, Pengbo

2017-06-03

Ketamine is commonly used for anesthesia in pediatric patients. Recent studies indicated that ketamine exposure in the developing brain can induce neuroapoptosis and disturb normal neurogenesis, which will result in long-lasting cognitive impairment. Minocycline exerts neuroprotection against a wide range of toxic insults in neurodegenerative disease models. In the present study, we investigated whether the disturbed neurogenesis and behavioral deficits after ketamine neonatal exposure could be alleviated by minocycline. Postnatal day (PND)7 Sprague-Dawley rat pups randomly received either normal saline, ketamine, or minocycline 30min prior to ketamine administration, respectively. The rats were decapitated at PND14 for the detection of neurogenesis in the subventricular zone (SVZ) and subgranular zone (SGZ) of the hippocampus by immunostaining. The protein expression of p-Akt, p-GSK-3β in the SVZ and SGZ at 12h after anesthesia, PND10 and PND14 were assessed by western blotting analysis. At PND 42-47, spatial learning and memory abilities were measured by the Morris water maze in all groups. Our data showed that ketamine exposure in neonatal rats resulted in neurogenetic damage and persistent cognitive deficits, and that pretreatment with minocycline eliminated the brain development damage and improved the behavioral function in adult rats. Moreover, the protection of minocycline is associated with the PI3K/Akt signaling pathway. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Pathophysiology of Depression: Molecular Regulation of Melatonin Homeostasis - Current Status.

PubMed

Dmitrzak-Weglarz, Monika; Reszka, Edyta

2018-06-13

Circadian rhythm alterations resulting in disturbed sleep and disturbed melatonin secretion are flagship features of depression. Melatonin, known as a hormone of darkness, is secreted by the pineal gland located near to the center of the brain between the two hemispheres. Melatonin has an antidepressant effect by maintaining the body's circadian rhythm, by regulating the pattern of expression of the clock genes in the suprachiasmatic nucleus (SCN) and modifying the key genes of serotoninergic neurotransmission that are linked with a depressive mood. Melatonin is produced via the metabolism of serotonin in two steps which are catalyzed by serotonin N-acetyltransferase (SNAT) and acetylserotonin-O-methyltransferase (ASMT). Serotonin, SNAT, and ASMT are key melatonin level regulation factors. Melatonin acts mainly on the MT1 and MT2 receptors, which are present in the SCN, to regulate physiological and neuroendocrine functions including circadian entrainment, referred to as a chronobiotic effect. Although melatonin has been known about and refereed to for almost 50 years, the relationship between melatonin and depression is still not clear. In this review, we summarize current knowledge about the genetic and epigenetic regulation of enzymes involved in melatonin synthesis and metabolism as potential features of depression pathophysiology and treatment. Confirmation that melatonin metabolism in peripheral blood partially reflects a disorder in the brain could be a breakthrough in the standardization of measurements of melatonin level for the development of treatment standards, finding new therapeutic targets, and elaborating simple noninvasive clinical tests. © 2018 S. Karger AG, Basel.

Long-term neuronal damage and recovery after a single dose of MDMA: expression and distribution of serotonin transporter in the rat brain.

PubMed

Kirilly, Eszter

2010-09-01

"Ecstasy", 3,4-methylenedioxymethamphetamine (MDMA), an amphetamine analogue is one of the most widely used recreational drugs. In spite of the fact that neurotoxic effects of MDMA has been found in several species from rodents to non-human primates, and results increasingly point to damage also in human MDMA users, data about the sensitivity of different brain areas and the recovery after neuronal damage are scarce. Serotonin transporter (5-HTT) mRNA in the raphe nuclei also has not been examined. Humans with genetic predisposition for the slow metabolism of MDMA, the so-called "poor metabolizers" of debrisoquin are at higher risk. Five- 9% of the Caucasian population is considered to carry this phenotype. These studies were carried out in Dark Agouti rats, a special strain that show decreased microsomal CYP2D1 isoenzyme activity, and thus may serve as a model of vulnerable human users. These works were designed to characterize MDMA-induced damage and recovery of the serotonergic system including sleep and morphological changes within 180 days. In our experiments we investigated the 5-HTT mRNA expression in the brainstem and medullary raphe nuclei, 5-HTT immunoreactive (IR) fibre densities in several brain areas, and 16 functional measures of sleep in response to a single dose of +/- MDMA (15mg\\kg). Furthermore, behavioural experiments were performed 21 days after MDMA treatment. We found similar changes in 5-HTT mRNA expression in the examined raphe nuclei, namely transient increases 7 days after MDMA treatment followed by transient decreases at 21 days. Significant (20-40%), widespread reductions in 5-HTT-IR fibre density were detected in most brain areas at 7 and 21 days after MDMA administration. All cortical, but only some brainstem areas were damaged. Parallel to the neuronal damage we observed significant reductions in rapid eye movement (REM) sleep latency, increased fragmentation of sleep and increases in delta power spectra in non-REM sleep. At 180 days almost all functional changes in sleep were normalized together with 5-HTT mRNA expression in the examined raphe nuclei and the recovery of 5-HTT-IR fibre density in most brain areas. Our results also suggest that the acute MDMA administration abolished aggressive behaviour but MDMA pretreatment and the consequent depletion of serotonergic terminals did not affect aggression. Our findings concerning the changes detected in 5-HTT mRNA expression and fibre density indicate lasting impairment of the serotonergic system and suggest that a single use of MDMA may be associated with long-lasting cognitive, learning, memory and mood deficits and sleep disturbances particularly when a constellation of genetic vulnerability and certain environmental factors are present. Our data provide further evidence for the connection between altered serotonergic functions and sleep disturbance.

Sleep Disorders Associated With Alzheimer's Disease: A Perspective

PubMed Central

Brzecka, Anna; Leszek, Jerzy; Ashraf, Ghulam Md; Ejma, Maria; Ávila-Rodriguez, Marco F.; Yarla, Nagendra S.; Tarasov, Vadim V.; Chubarev, Vladimir N.; Samsonova, Anna N.; Barreto, George E.; Aliev, Gjumrakch

2018-01-01

Sleep disturbances, as well as sleep-wake rhythm disturbances, are typical symptoms of Alzheimer's disease (AD) that may precede the other clinical signs of this neurodegenerative disease. Here, we describe clinical features of sleep disorders in AD and the relation between sleep disorders and both cognitive impairment and poor prognosis of the disease. There are difficulties of the diagnosis of sleep disorders based on sleep questionnaires, polysomnography or actigraphy in the AD patients. Typical disturbances of the neurophysiological sleep architecture in the course of the AD include deep sleep and paradoxical sleep deprivation. Among sleep disorders occurring in patients with AD, the most frequent disorders are sleep breathing disorders and restless legs syndrome. Sleep disorders may influence circadian fluctuations of the concentrations of amyloid-β in the interstitial brain fluid and in the cerebrovascular fluid related to the glymphatic brain system and production of the amyloid-β. There is accumulating evidence suggesting that disordered sleep contributes to cognitive decline and the development of AD pathology. In this mini-review, we highlight and discuss the association between sleep disorders and AD. PMID:29904334

The influence of encoding strategy on episodic memory and cortical activity in schizophrenia.

PubMed

Bonner-Jackson, Aaron; Haut, Kristen; Csernansky, John G; Barch, Deanna M

2005-07-01

Recent work suggests that episodic memory deficits in schizophrenia may be related to disturbances of encoding or retrieval. Schizophrenia patients appear to benefit from instruction in episodic memory strategies. We tested the hypothesis that providing effective encoding strategies to schizophrenia patients enhances encoding-related brain activity and recognition performance. Seventeen schizophrenia patients and 26 healthy comparison subjects underwent functional magnetic resonance imaging scans while performing incidental encoding tasks of words and faces. Subjects were required to make either deep (abstract/concrete) or shallow (alphabetization) judgments for words and deep (gender) judgments for faces, followed by subsequent recognition tests. Schizophrenia and comparison subjects recognized significantly more words encoded deeply than shallowly, activated regions in inferior frontal cortex (Brodmann area 45/47) typically associated with deep and successful encoding of words, and showed greater left frontal activation for the processing of words compared with faces. However, during deep encoding and material-specific processing (words vs. faces), participants with schizophrenia activated regions not activated by control subjects, including several in prefrontal cortex. Our findings suggest that a deficit in use of effective strategies influences episodic memory performance in schizophrenia and that abnormalities in functional brain activation persist even when such strategies are applied.

Symptom correlates of cerebral blood flow following acute concussion.

PubMed

Churchill, Nathan W; Hutchison, Michael G; Graham, Simon J; Schweizer, Tom A

2017-01-01

Concussion is associated with significant symptoms within hours to days post-injury, including disturbances in physical function, cognition, sleep and emotion. However, little is known about how subjective impairments correlate with objective measures of cerebrovascular function following brain injury. This study examined the relationship between symptoms and cerebral blood flow (CBF) in individuals following sport-related concussion. Seventy university level athletes had CBF measured using Arterial Spin Labelling (ASL), including 35 with acute concussion and 35 matched controls and their symptoms were assessed using the Sport Concussion Assessment Tool 3 (SCAT3). For concussed athletes, greater total symptom severity was associated with elevated posterior cortical CBF, although mean CBF was not significantly different from matched controls ( p  = 0.46). Examining symptom clusters, athletes reporting greater cognitive symptoms also had lower frontal and subcortical CBF, relative to athletes with greater somatic symptoms. The "cognitive" and "somatic" subgroups also exhibited significant differences in CBF relative to controls ( p  ≤ 0.026). This study demonstrates objective CBF correlates of symptoms in recently concussed athletes and shows that specific symptom clusters may have distinct patterns of altered CBF, significantly extending our understanding of the neurobiology of concussion and traumatic brain injury.

[Amotivational syndrome in organic solvent abusers].

PubMed

Ozaki, S; Wada, K

2001-01-01

Amotivational syndrome is a chronic psychiatric disorder characterized by a variety of changes in personality, emotions and cognitive functions such as lack of activity, inward-turning, avolition, apathy, incoherence, blunted affect, inability to concentrate and memory disturbance. The syndrome was first described among those patients with a history of longtime cannabis use in the 1960's. Since then, there have been several reports describing similar psychiatric disorders to amotivational syndrome among patients with the history of some other psychoactive substances use including solvents, methamphetamine and OTC cough syrups. Therefore, the syndrome has been recognized as one of the common psychiatric conditions that might develop in patients with a history of any psychoactive substance use. Recently, more attention has been paid to the biological basis of amotivational syndrome. Several studies using MRI, SPECT or neuropsychological measures have revealed white matter changes, hypoperfusion in the frontal cortex of the brain and impairment of frontal lobe function. Those findings suggest that amotivational syndrome might be related to "hypofrontality" of the brain. Although no specific treatments have been reported to be definitely effective for patients with amotivational syndrome, some neuroleptics with activating properties or antidepressants can be given appropriately to treat the chief symptoms of the patients.

Altered Cerebral Blood Flow Covariance Network in Schizophrenia.

PubMed

Liu, Feng; Zhuo, Chuanjun; Yu, Chunshui

2016-01-01

Many studies have shown abnormal cerebral blood flow (CBF) in schizophrenia; however, it remains unclear how topological properties of CBF network are altered in this disorder. Here, arterial spin labeling (ASL) MRI was employed to measure resting-state CBF in 96 schizophrenia patients and 91 healthy controls. CBF covariance network of each group was constructed by calculating across-subject CBF covariance between 90 brain regions. Graph theory was used to compare intergroup differences in global and nodal topological measures of the network. Both schizophrenia patients and healthy controls had small-world topology in CBF covariance networks, implying an optimal balance between functional segregation and integration. Compared with healthy controls, schizophrenia patients showed reduced small-worldness, normalized clustering coefficient and local efficiency of the network, suggesting a shift toward randomized network topology in schizophrenia. Furthermore, schizophrenia patients exhibited altered nodal centrality in the perceptual-, affective-, language-, and spatial-related regions, indicating functional disturbance of these systems in schizophrenia. This study demonstrated for the first time that schizophrenia patients have disrupted topological properties in CBF covariance network, which provides a new perspective (efficiency of blood flow distribution between brain regions) for understanding neural mechanisms of schizophrenia.

A Proposed Neurological Interpretation of Language Evolution.

PubMed

Ardila, Alfredo

2015-01-01

Since the very beginning of the aphasia history it has been well established that there are two major aphasic syndromes (Wernicke's-type and Broca's-type aphasia); each one of them is related to the disturbance at a specific linguistic level (lexical/semantic and grammatical) and associated with a particular brain damage localization (temporal and frontal-subcortical). It is proposed that three stages in language evolution could be distinguished: (a) primitive communication systems similar to those observed in other animals, including nonhuman primates; (b) initial communication systems using sound combinations (lexicon) but without relationships among the elements (grammar); and (c) advanced communication systems including word-combinations (grammar). It is proposed that grammar probably originated from the internal representation of actions, resulting in the creation of verbs; this is an ability that depends on the so-called Broca's area and related brain networks. It is suggested that grammar is the basic ability for the development of so-called metacognitive executive functions. It is concluded that while the lexical/semantic language system (vocabulary) probably appeared during human evolution long before the contemporary man (Homo sapiens sapiens), the grammatical language historically represents a recent acquisition and is correlated with the development of complex cognition (metacognitive executive functions).

A Proposed Neurological Interpretation of Language Evolution

PubMed Central

2015-01-01

Since the very beginning of the aphasia history it has been well established that there are two major aphasic syndromes (Wernicke's-type and Broca's-type aphasia); each one of them is related to the disturbance at a specific linguistic level (lexical/semantic and grammatical) and associated with a particular brain damage localization (temporal and frontal-subcortical). It is proposed that three stages in language evolution could be distinguished: (a) primitive communication systems similar to those observed in other animals, including nonhuman primates; (b) initial communication systems using sound combinations (lexicon) but without relationships among the elements (grammar); and (c) advanced communication systems including word-combinations (grammar). It is proposed that grammar probably originated from the internal representation of actions, resulting in the creation of verbs; this is an ability that depends on the so-called Broca's area and related brain networks. It is suggested that grammar is the basic ability for the development of so-called metacognitive executive functions. It is concluded that while the lexical/semantic language system (vocabulary) probably appeared during human evolution long before the contemporary man (Homo sapiens sapiens), the grammatical language historically represents a recent acquisition and is correlated with the development of complex cognition (metacognitive executive functions). PMID:26124540

The carbohydrate deposits detected by histochemical methods in the molecular layer of the dentate gyrus in the hippocampal formation of patients with schizophrenia, Down's syndrome and dementia, and aged person.

PubMed

Nishimura, A; Ikemoto, K; Satoh, K; Yamamoto, Y; Rand, S; Brinkmann, B; Nishi, K

2000-11-01

Post-mortem brain tissue was obtained from 28 patients with brain disorders, of which 15 had clinically diagnosed schizophrenia, 6 Alzheimer type dementia, 5 dementia with tangles and 2 cases of Down's syndrome. The controls were 22 cases from autopsies without brain disorders or with no known episodes of brain disorder. The tissues were stained for the detection of carbohydrate deposits in the hippocampal formation, using lectin, immunohistochemical and conventional staining methods. The staining revealed the existence of spherical deposits in the inner and middle molecular layers of the dentate gyrus in the hippocampal formation which contained fucose, galactose, N-acetyl galactosamine, N-acetyl glucosamine, sialic acid, mannose and chondroitin sulfate. The number of the deposits was higher in patients with brain disorder such as schizophrenia, Alzheimer type dementia, dementia with tangles or Down's syndrome, and in some aged individuals, in comparison to those in younger individuals. No deposits were detected in a few younger or aged individuals. Spherical deposits 3-10 microm in diameter may be an immature form of the corpora amylacea, since they were similar in the histochemical characteristics with lectin, immunohistochemical and conventional staining methods. However, differing staining ability by hematoxylin, periodic acid Schiff's reagent and antibodies against the intracellular degraded proteins such as ubiquitin and tau-protein was observed. The antibodies against ubiquitin and tau-protein showed clear reactivity with the corpora amylacea and no reactivity with spherical deposits, indicating that the corpora amylacea has an intracellular origin and spherical deposits an extracellular matrix origin. The results obtained in this study indicate that not only neuronal degeneration but also unusual glycometabolism in neurons may disturb the neuronal function and cause brain disorders, and that spherical deposits may cause dysfunction of the neuronal network in the dentate gyrus of the hippocampus which is closely linked with recognition and memory functions.

LRP1 in Brain Vascular Smooth Muscle Cells Mediates Local Clearance of Alzheimer's Amyloid-β

PubMed Central

Kanekiyo, Takahisa; Liu, Chia-Chen; Shinohara, Mitsuru; Li, Jie; Bu, Guojun

2012-01-01

Impaired clearance of amyloid-β (Aβ) is a major pathogenic event for Alzheimer’s disease (AD). Aβ depositions in brain parenchyma as senile plaques and along cerebrovasculature as cerebral amyloid angiopathy (CAA) are hallmarks of AD. A major pathway that mediates brain Aβ clearance is the cerebrovascular system where Aβ is eliminated through the blood-brain barrier (BBB) and/or degraded by cerebrovascular cells along the interstitial fluid drainage pathway. An Aβ clearance receptor, the low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in cerebrovasculature, in particular in vascular smooth muscle cells. Previous studies have indicated a role of LRP1 in endothelial cells in transcytosing Aβ out of the brain across the BBB; however, whether this represents a significant pathway for brain Aβ clearance remains controversial. Here, we demonstrate that Aβ can be cleared locally in the cerebrovasculature by an LRP1-dependent endocytic pathway in smooth muscle cells. The uptake and degradation of both endogenous and exogenous Aβ were significantly reduced in LRP1-suppressed human brain vascular smooth muscle cells. Conditional deletion of Lrp1 in vascular smooth muscle cell in amyloid model APP/PS1 mice accelerated brain Aβ accumulation and exacerbated Aβ deposition as amyloid plaques and CAA without affecting Aβ production. Our results demonstrate that LRP1 is a major Aβ clearance receptor in cerebral vascular smooth muscle cell and a disturbance of this pathway contributes to Aβ accumulation. These studies establish critical functions of the cerebrovasculature system in Aβ metabolism and identify a new pathway involved in the pathogenesis of both AD and CAA. PMID:23152628

GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia

PubMed Central

Gonzalez-Burgos, Guillermo; Fish, Kenneth N.; Lewis, David A.

2011-01-01

Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions. PMID:21904685

Sleep disturbances in individuals at clinical high risk for psychosis

PubMed Central

Poe, Sarah-Lucy; Brucato, Gary; Bruno, Nicolina; Arndt, Leigh Y.; Ben-David, Shelly; Gill, Kelly E.; Colibazzi, Tiziano; Kantrowitz, Joshua T.; Corcoran, Cheryl M.; Girgis, Ragy R.

2018-01-01

There has been recent interest in understanding the role that sleep disturbance plays in patients at Clinical High Risk for psychosis (CHR). We assessed sleep disturbance in 194 CHR patients and 66 healthy control subjects and their relationship to symptoms (positive, negative and general functioning). Patients experienced significantly more sleep disturbance than healthy control subjects and their sleep disturbance was related to greater positive and negative symptoms and worse overall functioning. Targeting sleep disturbance in CHR individuals may provide alternative means of treating the CHR syndrome. PMID:28126579

Dysfunction in endoplasmic reticulum-mitochondria crosstalk underlies SIGMAR1 loss of function mediated motor neuron degeneration.

PubMed

Bernard-Marissal, Nathalie; Médard, Jean-Jacques; Azzedine, Hamid; Chrast, Roman

2015-04-01

Mutations in Sigma 1 receptor (SIGMAR1) have been previously identified in patients with amyotrophic lateral sclerosis and disruption of Sigmar1 in mouse leads to locomotor deficits. However, cellular mechanisms underlying motor phenotypes in human and mouse with disturbed SIGMAR1 function have not been described so far. Here we used a combination of in vivo and in vitro approaches to investigate the role of SIGMAR1 in motor neuron biology. Characterization of Sigmar1(-/-) mice revealed that affected animals display locomotor deficits associated with muscle weakness, axonal degeneration and motor neuron loss. Using primary motor neuron cultures, we observed that pharmacological or genetic inactivation of SIGMAR1 led to motor neuron axonal degeneration followed by cell death. Disruption of SIGMAR1 function in motor neurons disturbed endoplasmic reticulum-mitochondria contacts, affected intracellular calcium signalling and was accompanied by activation of endoplasmic reticulum stress and defects in mitochondrial dynamics and transport. These defects were not observed in cultured sensory neurons, highlighting the exacerbated sensitivity of motor neurons to SIGMAR1 function. Interestingly, the inhibition of mitochondrial fission was sufficient to induce mitochondria axonal transport defects as well as axonal degeneration similar to the changes observed after SIGMAR1 inactivation or loss. Intracellular calcium scavenging and endoplasmic reticulum stress inhibition were able to restore mitochondrial function and consequently prevent motor neuron degeneration. These results uncover the cellular mechanisms underlying motor neuron degeneration mediated by loss of SIGMAR1 function and provide therapeutically relevant insight into motor neuronal diseases. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of mental rotation on acalculia: differences in the direction of mental rotation account for the differing characteristics of acalculia induced by right and left hemispheric brain injury.

PubMed

Asada, Tomohiko; Takayama, Yoshihiro; Oita, Jiro; Fukuyama, Hidenao

2014-04-01

We observed a 59-year-old right-handed man with an infarction in his right-middle cerebral artery that included the parietal lobe, who abnormally manipulated mental images in the horizontal direction, resulting in calculation disturbances. Three years later, the patient suffered an infarction in the left parietal lobe and displayed abnormalities during the creation of mental images; i.e., he rotated them in the vertical direction, which again resulted in calculation disturbances. These mental imagery disturbances might indicate that a common acalculia mechanism exists between the right and left hemispheres.

N-methyl-d-aspartate receptors, learning and memory: chronic intraventricular infusion of the NMDA receptor antagonist d-AP5 interacts directly with the neural mechanisms of spatial learning.

PubMed

Morris, R G M; Steele, R J; Bell, J E; Martin, S J

2013-03-01

Three experiments were conducted to contrast the hypothesis that hippocampal N-methyl-d-aspartate (NMDA) receptors participate directly in the mechanisms of hippocampus-dependent learning with an alternative view that apparent impairments of learning induced by NMDA receptor antagonists arise because of drug-induced neuropathological and/or sensorimotor disturbances. In experiment 1, rats given a chronic i.c.v. infusion of d-AP5 (30 mm) at 0.5 μL/h were selectively impaired, relative to aCSF-infused animals, in place but not cued navigation learning when they were trained during the 14-day drug infusion period, but were unimpaired on both tasks if trained 11 days after the minipumps were exhausted. d-AP5 caused sensorimotor disturbances in the spatial task, but these gradually worsened as the animals failed to learn. Histological assessment of potential neuropathological changes revealed no abnormalities in d-AP5-treated rats whether killed during or after chronic drug infusion. In experiment 2, a deficit in spatial learning was also apparent in d-AP5-treated rats trained on a spatial reference memory task involving two identical but visible platforms, a task chosen and shown to minimise sensorimotor disturbances. HPLC was used to identify the presence of d-AP5 in selected brain areas. In Experiment 3, rats treated with d-AP5 showed a delay-dependent deficit in spatial memory in the delayed matching-to-place protocol for the water maze. These data are discussed with respect to the learning mechanism and sensorimotor accounts of the impact of NMDA receptor antagonists on brain function. We argue that NMDA receptor mechanisms participate directly in spatial learning. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Alcohol-induced one-carbon metabolism impairment promotes dysfunction of DNA base excision repair in adult brain.

PubMed

Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J; Bergeson, Susan E; Henderson, George I; Kruman, Inna I

2012-12-21

The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr(+/-) mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain.

Beyond classic ecological assessment: The use of functional indices to indicate fish assemblages sensitivity to human disturbance in estuaries.

PubMed

Teichert, Nils; Lepage, Mario; Lobry, Jérémy

2018-10-15

Assessing ecological health of aquatic ecosystems is crucial in the current context of biodiversity loss to guide and prioritize management actions. Although several fish-based indices were developed to assess the ecological status of estuarine ecosystems, they do not provide guidance on the causal responses of communities to disturbances. The functional trait-based approach provides an understanding of how human disturbance affects the composition of biological and ecological traits in assemblages, as well as their consequences for ecosystem functioning. Here, we evaluate the responses of fish assemblages to human disturbance in 30 French estuaries using several taxonomic and functional indices (e.g. diversity, evenness or redundancy). We tested whether these indices can provide additional information on the human impacts and health of assemblages that are not reflected by the ecological indicator (fish-based index ELFI). Results indicated that high values of local human disturbances were associated to a decrease in fish abundance, decrease in species richness and reduced functional redundancy, whereas taxonomic and functional evenness increased. In contrast, the functional richness remained stable suggesting that the functional traits of species removed by stressors were maintained by more tolerant species. Indeed, we found that the local disturbances mainly resulted in a decrease in the proportions of small benthic species feeding on macro-invertebrates, which were dominant in the studied estuaries. Some functional alterations were detected by the fish-based index, but the decline of functional redundancy was not reflected, highlighting a serious concern for management. Indeed, the abrupt collapse of functional redundancy in response to local disturbances can decrease the ability of assemblages to maintain certain species traits in the face of future environmental disturbance, including climate change. From a management perspective, the application of such functional redundancy measure in monitoring programs can help stakeholders identify sensitive areas where conservation efforts need to be planned. Copyright © 2018 Elsevier B.V. All rights reserved.

Physiological Observations and Omics to Develop Personalized Sensormotor Adaptability Countermeasures Using Bed Rest and Space Flight Data

NASA Technical Reports Server (NTRS)

Mulavara, A. P.; Seidler, R. D.; Feiveson, A.; Oddsson, L.; Zanello, S.; Oman, C. M.; Ploutz-Snyder, L.; Peters, B.; Cohen, H. S.; Reschke, M.;

Repeated disturbances affect functional but not compositional resistance and resilience in an aquatic bacterioplankton community.

PubMed

Sjöstedt, Johanna; Langenheder, Silke; Kritzberg, Emma; Karlsson, Christofer M G; Lindström, Eva S

2018-05-07

Disturbances are believed to be one of the main factors influencing variations in community diversity and functioning. Here we investigated if exposure to a pH press disturbance affected the composition and functional performance of a bacterial community and its resistance, recovery and resilience to a second press disturbance (salt addition). Lake bacterial assemblages were initially exposed to reduced pH in six mesocosms whereas another six mesocosms were kept as reference. Seven days after the pH disturbance, three tanks from each treatment were exposed to a salt disturbance. Both bacterial production and enzyme activity were negatively affected by the salt treatment, regardless if the communities had been subject to a previous disturbance or not. However, cell-specific enzyme activity had a higher resistance in communities pre-exposed to the pH disturbance compared to the reference treatment. In contrast, for cell-specific bacterial production resistance was not affected, but recovery was faster in the communities that had previously been exposed to the pH disturbance. Over time, bacterial community composition diverged among treatments, in response to both pH and salinity. The difference in functional recovery, resilience and resistance may depend on differences in community composition caused by the pH disturbance, niche breadth or acquired stress resistance. This article is protected by copyright. All rights reserved. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

Effects of different types of moderate severity disturbance on forest structural complexity and ecosystem functioning: A story of ice and fire

NASA Astrophysics Data System (ADS)

Fahey, R. T.; Atkins, J.; Gough, C. M.; Hardiman, B. S.; Haber, L.; Stuart-Haentjens, E.; David, O.; Campbell, J. L.; Rustad, L.; Duffy, M.

2017-12-01

Disturbances that alter the structure and function of forest ecosystems occur along a continuum of severity. In contrast to the extremes of the disturbance gradient (i.e., stand-replacing disturbance and small gap formation), moderate severity disturbances are poorly understood, even though they make up the majority of the gradient and their spatial extent (and likely overall importance to regional disturbance regimes) often exceeds that of more severe disturbances. Moderate severity disturbances originate from a variety of causes, such as fires, ice storms, or pest and pathogen outbreaks, and each of these could reshape structure and function in different ways. Observational data from a limited number of sites shows that moderate disturbance can increase ecosystem complexity, but the generality of this effect has not been tested across a broad range of disturbance types and severities. Here, we utilize data from a set of five case studies of experimental or natural moderate disturbance to assess the effects of different types and severities of disturbance on forest canopy structural complexity (CSC) and the relationship of canopy structure with ecosystem functioning. Using pre- and post-disturbance measures of CSC derived from aerial and terrestrial LiDAR, UAV imagery, and Landsat data we quantified changes in CSC following an experimental ice storm, a low-severity surface fire, Beech Bark Disease and Hemlock Wooly Adelgid outbreaks, and experimental accelerated succession. Our initial findings indicate that different disturbance types have highly variable effects on CSC, and also that progressive increases in disturbance severity alter CSC differently among disturbance types. Differential effects of variable disturbance types on CSC has implications for the carbon cycle, as forest structure is strongly linked with both growth-limiting resource (e.g., nutrients and light) acquisition and net primary productivity. Understanding how different types and severities of moderate disturbance affect canopy structural complexity is thus crucial to informing and improving modeling the earth system and predicting how global shifts in moderate disturbance type, frequency, and severity will alter the land carbon sink.

Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation.

PubMed

Ravindran, Ethiraj; Hu, Hao; Yuzwa, Scott A; Hernandez-Miranda, Luis R; Kraemer, Nadine; Ninnemann, Olaf; Musante, Luciana; Boltshauser, Eugen; Schindler, Detlev; Hübner, Angela; Reinecker, Hans-Christian; Ropers, Hans-Hilger; Birchmeier, Carmen; Miller, Freda D; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M

2017-04-01

Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures. Rho guanine nucleotide exchange factor (ARHGEF) family members are key for controlling the spatiotemporal activation of Rho GTPase, to modulate cytoskeleton dynamics, cell division, and cell migration. We identified, by means of whole exome sequencing, a homozygous frameshift mutation in the ARHGEF2 as a cause of intellectual disability, a midbrain-hindbrain malformation, and mild microcephaly in a consanguineous pedigree of Kurdish-Turkish descent. We show that loss of ARHGEF2 perturbs progenitor cell differentiation and that this is associated with a shift of mitotic spindle plane orientation, putatively favoring more symmetric divisions. The ARHGEF2 mutation leads to reduction in the activation of the RhoA/ROCK/MLC pathway crucial for cell migration. We demonstrate that the human brain malformation is recapitulated in Arhgef2 mutant mice and identify an aberrant migration of distinct components of the precerebellar system as a pathomechanism underlying the midbrain-hindbrain phenotype. Our results highlight the crucial function of ARHGEF2 in human brain development and identify a mutation in ARHGEF2 as novel cause of a neurodevelopmental disorder.

Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation

PubMed Central

Yuzwa, Scott A.; Hernandez-Miranda, Luis R.; Musante, Luciana; Boltshauser, Eugen; Schindler, Detlev; Hübner, Angela; Reinecker, Hans-Christian; Ropers, Hans-Hilger; Miller, Freda D.; Hübner, Christoph; Kaindl, Angela M.

2017-01-01

Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures. Rho guanine nucleotide exchange factor (ARHGEF) family members are key for controlling the spatiotemporal activation of Rho GTPase, to modulate cytoskeleton dynamics, cell division, and cell migration. We identified, by means of whole exome sequencing, a homozygous frameshift mutation in the ARHGEF2 as a cause of intellectual disability, a midbrain-hindbrain malformation, and mild microcephaly in a consanguineous pedigree of Kurdish-Turkish descent. We show that loss of ARHGEF2 perturbs progenitor cell differentiation and that this is associated with a shift of mitotic spindle plane orientation, putatively favoring more symmetric divisions. The ARHGEF2 mutation leads to reduction in the activation of the RhoA/ROCK/MLC pathway crucial for cell migration. We demonstrate that the human brain malformation is recapitulated in Arhgef2 mutant mice and identify an aberrant migration of distinct components of the precerebellar system as a pathomechanism underlying the midbrain-hindbrain phenotype. Our results highlight the crucial function of ARHGEF2 in human brain development and identify a mutation in ARHGEF2 as novel cause of a neurodevelopmental disorder. PMID:28453519

An overview of concussion in sport.

PubMed

Khurana, Vini G; Kaye, Andrew H

2012-01-01

Concussion is a sudden-onset, transient alteration of consciousness due to a combination of functional and structural brain disturbances following a physical impact transmitted to the brain. It is a common, although likely underreported, condition encountered in a wide range of sports. In the Australian Football League, concussion is estimated to occur at a rate of approximately seven injuries per team per season. While many instances of concussion are clinically mild, there is emerging evidence that a player's full recovery from a concussive injury may be more delayed and the sequelae of repeated concussions more severe than previously thought. In this light, a more conservative and rigorous approach to managing players with concussive injuries may be warranted, with the guiding principle being the player's immediate and long-term welfare. The current paper reviews the sports concussion literature. The definition, epidemiology, aetiology, pathophysiology, structural pathology, clinical features, assessment and investigation, treatment principles, and short-term and potential long-term complications of concussion are discussed. Special considerations in paediatric sports concussion, and the return-to-play implications of immediate, evolving and repetitive brain injury are also considered, as are the emerging concept and possible implications of subconcussive injury. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Novel c-Jun N-terminal Kinase (JNK) Signaling Complex Involved in Neuronal Migration during Brain Development.

PubMed

Zhang, Feng; Yu, Jingwen; Yang, Tao; Xu, Dan; Chi, Zhixia; Xia, Yanheng; Xu, Zhiheng

2016-05-27

Disturbance of neuronal migration may cause various neurological disorders. Both the transforming growth factor-β (TGF-β) signaling and microcephaly-associated protein WDR62 are important for neuronal migration during brain development; however, the underlying molecular mechanisms involved remain unclear. We show here that knock-out or knockdown of Tak1 (TGFβ-activated kinase 1) and Jnk2 (c-Jun N-terminal kinase 2) perturbs neuronal migration during cortical development and that the migration defects incurred by knock-out and/or knockdown of Tβr2 (type II TGF-β receptor) or Tak1 can be partially rescued by expression of TAK1 and JNK2, respectively. Furthermore, TAK1 forms a protein complex with RAC1 and two scaffold proteins of the JNK pathway, the microcephaly-associated protein WDR62 and the RAC1-interacting protein POSH (plenty of Src homology). Components of the complex coordinate with each other in the regulation of TAK1 as well as JNK activities. We suggest that unique JNK protein complexes are involved in the diversified biological and pathological functions during brain development and pathogenesis of diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Do Quercus ilex Woodlands Undergo Abrupt Non-linear Changes in their Functional Dynamics in Response to Human Disturbance and Climatic Variation?

NASA Astrophysics Data System (ADS)

Bochet, E.; García-Fayos, P.; Molina, M. J.; Moreno de las Heras, M.; Espigares, T.; Nicolau, J. M.; Monleon, V. J.

2017-12-01

Theoretical models predict that drylands are particularly prone to suffer critical transitions with abrupt non-linear changes in their structure and functions as a result of the existing complex interactions between climatic fluctuations and human disturbances. How drylands undergo functional change has become an important issue in ecology which needs empirical data to validate theoretical models. We aim at determining the response of Mediterranean holm oak woodlands to human disturbance in three different climatic areas from Eastern Spain, under the hypothesis that semiarid and dry-transition landscapes are more prone to suffer abrupt functional changes than sub-humid ones. We used (a) remote-sensing estimations of precipitation-use-efficiency (PUE) from enhanced vegetation index (EVI) observations performed in 231 x 231 m plots of the Moderate Resolution Imaging Spectroradiometer (MODIS); (b) soil parameter (enzyme activity, organic matter) and (c) vegetation parameter (functional groups) determinations from soil sampling and vegetation surveys, respectively, performed in the same plots. We analyzed and compared the shape of the functional change (in terms of PUE, soil and vegetation parameters) in response to human disturbance intensity for our holm oak sites in the three climatic areas. Although no threshold of abrupt change is observed, important differences in the functional response of holm oak woodlands to disturbance exist between climatic conditions. Overall, semiarid and dry-transition woodlands suffer a non-linear functional decrease in terms of PUE, soil organic matter and enzyme activity with disturbance intensity. Differently, sub-humid woodlands experience a linear decrease of PUE with disturbance intensity and an increase of both soil parameters at high disturbance intensities after an important decrease at low disturbance intensities. The structural change from woody- to herbaceous-dominated landscapes in sub-humid areas explains the recovery of the functional state of the system at high disturbance intensities. This structural change in the vegetation provides resilience to sub-humid woodlands at high intensity levels where semiarid and dry-transition woodlands suffer a pronounced degradation.

Developing Personalized Sensorimotor Adaptability Countermeasures for Spaceflight

NASA Technical Reports Server (NTRS)

Mulavara, A. P.; Seidler, R. D.; Peters, B.; Cohen, H. S.; Wood, S.; Bloomberg, J. J.

2016-01-01

Astronauts experience sensorimotor disturbances during their initial exposure to microgravity and during the re-adaptation phase following a return to an Earth-gravitational environment. Interestingly, astronauts who return from spaceflight show substantial differences in their abilities to readapt to a gravitational environment. The ability to predict the manner and degree to which individual astronauts would be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. In this paper we will be presenting results from our ground-based study that show how behavioral, brain imaging and genomic data may be used to predict individual differences in sensorimotor adaptability to novel sensorimotor environments. This approach will allow us to better design and implement sensorimotor adaptability training countermeasures against decrements in post-mission adaptive capability that are customized for each crewmember's sensory biases, adaptive capacity, brain structure, functional capacities, and genetic predispositions. The ability to customize adaptability training will allow more efficient use of crew time during training and will optimize training prescriptions for astronauts to ensure expected outcomes.

Mind-language in the age of the brain: is "mental illness" a useful term?

PubMed

Pies, Ronald

2015-01-01

The term "mental illness" has been criticized on a variety of grounds, most notably by those who have argued that the term is merely a "myth" or a "metaphor." Some have argued that if and when so-called mental illnesses are exhaustively explained by disturbed brain function or structure, we will no longer need the term "mental illness," on the supposition that neuropathology and psychopathology are mutually exclusive constructs. The author argues that, on the contrary, the locution "mental illness" is not rendered useless or unnecessary when neuropathology is discovered, nor is the term "mental illness" a metaphor. Rather, it is an instance of "ordinary language" that we apply quite literally to certain types of suffering and incapacity in the realm of thought, emotion, cognition, and behavior. Although its use carries the risk of perpetuating mind-body dualism and it may be misused as a pejorative label, "mental illness" is likely to remain a useful and meaningful descriptive term, even as we discover the neurobiological underpinnings of psychiatric illness.

Working Memory Performance Is Correlated with Local Brain Morphology in the Medial Frontal and Anterior Cingulate Cortex in Fibromyalgia Patients: Structural Correlates of Pain-Cognition Interaction

ERIC Educational Resources Information Center

Luerding, R.; Weigand, T.; Bogdahn, U.; Schmidt-Wilcke, T.

2008-01-01

Fibromyalgia (FM) is a disorder of unknown aetiology, characterized by chronic widespread pain, stiffness and sleep disturbances. In addition, patients frequently complain of memory and attention deficits. Accumulating evidence suggests that FM is associated with CNS dysfunction and with an altered brain morphology. However, few studies have…

The role of sleep on cognition and functional connectivity in patients with multiple sclerosis.

PubMed

van Geest, Quinten; Westerik, B; van der Werf, Y D; Geurts, J J G; Hulst, H E

2017-01-01

Sleep disturbances are common in multiple sclerosis (MS), but its impact on cognition and functional connectivity (FC) of the hippocampus and thalamus is unknown. Therefore, we investigated the relationship between sleep disturbances, cognitive functioning and resting-state (RS) FC of the hippocampus and thalamus in MS. 71 MS patients and 40 healthy controls underwent neuropsychological testing and filled out self-report questionnaires (anxiety, depression, fatigue, and subjective cognitive problems). Sleep disturbances were assed with the five-item version of the Athens Insomnia Scale. Hippocampal and thalamic volume and RS FC of these regions were determined. Twenty-three patients were categorized as sleep disturbed and 48 as normal sleeping. No differences were found between disturbed and normal sleeping patients concerning cognition and structural MRI. Sleep disturbed patients reported more subjective cognitive problems, and displayed decreased FC between the thalamus and middle and superior frontal gyrus, inferior frontal operculum, anterior cingulate cortex, inferior parietal gyrus, precuneus, and angular gyrus compared to normal sleeping patients. We conclude that sleep disturbances in MS are not (directly) related to objective cognitive functioning, but rather to subjective cognitive problems. In addition, sleep disturbances in MS seem to coincide with a specific pattern of decreased thalamic FC.

Analysis of masking effects on speech intelligibility with respect to moving sound stimulus

NASA Astrophysics Data System (ADS)

Chen, Chiung Yao

2004-05-01

The purpose of this study is to compare the disturbed degree of speech by an immovable noise source and an apparent moving one (AMN). In the study of the sound localization, we found that source-directional sensitivity (SDS) well associates with the magnitude of interaural cross correlation (IACC). Ando et al. [Y. Ando, S. H. Kang, and H. Nagamatsu, J. Acoust. Soc. Jpn. (E) 8, 183-190 (1987)] reported that potential correlation between left and right inferior colliculus at auditory path in the brain is in harmony with the correlation function of amplitude input into two ear-canal entrances. We assume that the degree of disturbance under the apparent moving noisy source is probably different from that being installed in front of us within a constant distance in a free field (no reflection). Then, we found there is a different influence on speech intelligibility between a moving and a fixed source generated by 1/3-octave narrow-band noise with the center frequency 2 kHz. However, the reasons for the moving speed and the masking effects on speech intelligibility were uncertain.

Managing Sports-related Concussions From Time of Injury Through Return to Play.

PubMed

Shirley, Eric; Hudspeth, L Jared; Maynard, Jennifer R

2018-06-01

Sports-related concussions continue to generate widespread interest. A concussion is a complex pathophysiologic process, with or without loss of consciousness, that results in a disturbance of brain function. Risk factors include age <18 years, female sex, and history of a previous concussion. A sideline physical examination with standardized assessment tools can assist diagnosis. Management for suspected concussion begins with immediate removal from play and requires clinical follow-up. Symptoms are usually self-limited and resolve within 2 to 3 weeks. Initial treatment consists of a reduction in cognitive activity and physical rest. A stepwise return-to-play protocol, taking into consideration state laws, with a gradual increase in activity until the athlete is able to perform full activity without symptoms should be followed. Neuropsychologic testing may be used as a tool in management. For prolonged concussion, physical rehabilitation or medications for headaches, mood, or sleep disturbance may be required. Education, rule changes, and equipment improvements may assist in prevention. The long-term consequences of concussions are not fully understood and merit additional research.

Enduring disturbances in regional cerebral blood flow and brain oxygenation at 24 h after asphyxial cardiac arrest in developing rats.

PubMed

Foley, Lesley M; Clark, Robert S B; Vazquez, Alberto L; Hitchens, T Kevin; Alexander, Henry; Ho, Chien; Kochanek, Patrick M; Manole, Mioara D

2017-01-01

Disturbances in cerebral blood flow (CBF) and brain oxygenation (PbO 2 ) are present early after pediatric cardiac arrest (CA). CBF-targeted therapies improved neurological outcome in our CA model. To assess the therapeutic window for CBF- and PbO 2 -targeted therapies, we propose to determine if CBF and PbO 2 disturbances persist at 24 h after experimental pediatric CA. Regional CBF and PbO 2 were measured at 24 h after asphyxial CA in immature rats (n = 26, 6-8/group) using arterial spin label MRI and tissue electrodes, respectively. In all regions but the thalamus, CBF recovered to sham values by 24 h; thalamic CBF was >32% higher after CA vs. sham. PbO 2 values at 24 h after CA in the cortex and thalamus were similar to shams in rats who received supplemental oxygen, however, on room air, cortical PbO 2 was lower after CA vs. shams. CBF remains increased in the thalamus at 24 h after CA and PbO 2 is decreased to hypoxic levels in cortex at 24 h after CA in rats who do not receive supplemental oxygen. Given the enduring disturbances in this model and the lack of routine CBF or PbO 2 monitoring in patients, our data suggest the need for clinical correlation.

Sleep disturbances in individuals at clinical high risk for psychosis.

PubMed

Poe, Sarah-Lucy; Brucato, Gary; Bruno, Nicolina; Arndt, Leigh Y; Ben-David, Shelly; Gill, Kelly E; Colibazzi, Tiziano; Kantrowitz, Joshua T; Corcoran, Cheryl M; Girgis, Ragy R

2017-03-01

There has been recent interest in understanding the role that sleep disturbance plays in patients at Clinical High Risk for psychosis (CHR). We assessed sleep disturbance in 194 CHR patients and 66 healthy control subjects and their relationship to symptoms (positive, negative and general functioning). Patients experienced significantly more sleep disturbance than healthy control subjects and their sleep disturbance was related to greater positive and negative symptoms and worse overall functioning. Targeting sleep disturbance in CHR individuals may provide alternative means of treating the CHR syndrome. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Acute Brain Failure: Pathophysiology, Diagnosis, Management, and Sequelae of Delirium.

PubMed

Maldonado, José R

2017-07-01

Delirium is the most common psychiatric syndrome found in the general hospital setting, with an incidence as high as 87% in the acute care setting. Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances. The development of delirium is associated with increased morbidity, mortality, cost of care, hospital-acquired complications, placement in specialized intermediate and long-term care facilities, slower rate of recovery, poor functional and cognitive recovery, decreased quality of life, and prolonged hospital stays. This article discusses the epidemiology, known etiological factors, presentation and characteristics, prevention, management, and impact of delirium. Copyright © 2017 Elsevier Inc. All rights reserved.

Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome.

PubMed

Walton, Mark M G; Pallus, Adam; Fleuriet, Jérome; Mustari, Michael J; Tarczy-Hornoch, Kristina

2017-07-01

Infantile strabismus is characterized by numerous visual and oculomotor abnormalities. Recently nonhuman primate models of infantile strabismus have been established, with characteristics that closely match those observed in human patients. This has made it possible to study the neural basis for visual and oculomotor symptoms in infantile strabismus. In this review, we consider the available evidence for neural abnormalities in structures related to oculomotor pathways ranging from visual cortex to oculomotor nuclei. These studies provide compelling evidence that a disturbance of binocular vision during a sensitive period early in life, whatever the cause, results in a cascade of abnormalities through numerous brain areas involved in visual functions and eye movements. Copyright © 2017 the American Physiological Society.

Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges (SIRPIDs).

PubMed

Johnson, Emily L; Kaplan, Peter W; Ritzl, Eva K

2018-05-01

Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) are a relatively common phenomenon found on prolonged electroencephalogram (EEG) monitoring that captures state changes and stimulation of critically ill patients. Common causes include hypoxic injury, traumatic brain injury, and hemorrhage, as well as toxic-metabolic disturbances. Some studies have shown an association between SIRPIDs and the presence of spontaneous electrographic seizures. Although the degree to which SIRPIDs should be treated with antiepileptic medications is unknown, the rare cases of functional imaging obtained in patients with SIRPIDs have not shown an increase in cerebral blood flow to suggest an active ictal process. Stimulus-induced rhythmic, periodic, or ictal discharges may reflect dysregulation of thalamo-cortical projections into abnormal or hyperexcitable cortex.

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

Effect of tryptophan-rich egg protein hydrolysate on brain tryptophan availability, stress and performance.

PubMed

Markus, C Rob; Verschoor, E; Firk, C; Kloek, J; Gerhardt, C C

2010-10-01

Reduced brain serotonin function is involved in stress-related disturbances and may particularly occur under chronic stress. Although serotonin production directly depends on the availability of its plasma dietary amino acid precursor tryptophan (TRP), previously described effects of tryptophan-rich food sources on stress-related behavior are rather modest. Recently, an egg protein hydrolysate (EPH) was developed that showed a much greater effect on brain TRP availability than pure TRP and other TRP-food sources and therefore may be more effective for performance under stress. The aim of the present study was to investigate the effects of EPH compared to placebo protein on plasma amino acids, stress coping and performance in subjects with high and low chronic stress vulnerabilities. In a placebo-controlled, double-blind, crossover study, 17 participants with high and 18 participants with low chronic stress vulnerabilities were monitored for mood and performance under acute stress exposure either following intake of EPH or placebo. EPH significantly increased plasma TRP availability for uptake into the brain, decreased depressive mood in all subjects and improved perceptual-motor and vigilance performance only in low chronic stress-vulnerable subjects. The acute use of a TRP-rich egg protein hydrolysate (EPH) is an adequate method to increase plasma TRP for uptake into the brain and may be beneficial for perceptual-motor and vigilance performance in healthy volunteers. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Perspectives and new aspects of metalloproteinases' inhibitors in therapy of CNS disorders: from chemistry to medicine.

PubMed

Boguszewska-Czubara, Anna; Budzynska, Barbara; Skalicka-Wozniak, Krystyna; Kurzepa, Jacek

2018-05-13

Matrix metalloproteinases (MMPs) play a key role in remodelling of the extracellular matrix (ECM) and, at the same time, influence cell differentiation, migration, proliferation and survival. Their importance in variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders has been known for many years but special attention should be paid on the role of MMPs in the central nervous system (CNS) disorders. Till now, there are not many well documented physiological MMP target proteins in the brain and only some pathological ones. Numerous neurodegenerative diseases is a consequence or result in disturbed remodeling of brain ECM, therefore proper action of MMPs as well as control of their activity may play crucial roles in the development and the progress of these diseases. In present review we discuss the role of metalloproteinase inhibitors, from the well-known natural endogenous tissue inhibitors of metalloproteinases (TIMPs) through exogenous synthetic ones like (4-phenoxyphenylsulfonyl)methylthiirane (SB-3CT), tetracyclines, batimastat (BB-94) and FN-439. As the MMP-TIMP system has been well described in physiological development as well as in pathological conditions mainly in neoplasctic diseases, the knowledge about the enzymatic system in mammalian brain tissue remain still poorly understood in this context. Therefore, we focus on MMPs inhibition in the context of physiological function of adult brain as well as pathological conditions including neurodegenerative diseases, brain injuries and others. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Prenatal exposure to common environmental factors affects brain lipids and increases risk of developing autism spectrum disorders.

PubMed

Wong, Christine T; Wais, Joshua; Crawford, Dorota A

2015-11-01

The prevalence of autism spectrum disorders (ASDs) has been on the rise over recent years. The presence of diverse subsets of candidate genes in each individual with an ASD and the vast variability of phenotypical differences suggest that the interference of an exogenous environmental component may greatly contribute to the development of ASDs. The lipid mediator prostaglandin E2 (PGE2 ) is released from phospholipids of cell membranes, and is important in brain development and function; PGE2 is involved in differentiation, synaptic plasticity and calcium regulation. The previous review already described extrinsic factors, including deficient dietary supplementation, and exposure to oxidative stress, infections and inflammation that can disrupt signaling of the PGE2 pathway and contribute to ASDs. In this review, the structure and establishment of two key protective barriers for the brain during early development are described: the blood-brain barrier; and the placental barrier. Then, the first comprehensive summary of other environmental factors, such as exposure to chemicals in air pollution, pesticides and consumer products, which can also disturb PGE2 signaling and increase the risk for developing ASDs is provided. Also, how these exogenous agents are capable of crossing the protective barriers of the brain during critical developmental periods when barrier components are still being formed is described. This review underlines the importance of avoiding or limiting exposure to these factors during vulnerable periods in development. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Mammalian engineers drive soil microbial communities and ecosystem functions across a disturbance gradient.

PubMed

Eldridge, David J; Delgado-Baquerizo, Manuel; Woodhouse, Jason N; Neilan, Brett A

2016-11-01

The effects of mammalian ecosystem engineers on soil microbial communities and ecosystem functions in terrestrial ecosystems are poorly known. Disturbance from livestock has been widely reported to reduce soil function, but disturbance by animals that forage in the soil may partially offset these negative effects of livestock, directly and/or indirectly by shifting the composition and diversity of soil microbial communities. Understanding the role of disturbance from livestock and ecosystem engineers in driving soil microbes and functions is essential for formulating sustainable ecosystem management and conservation policies. We compared soil bacterial community composition and enzyme concentrations within four microsites: foraging pits of two vertebrates, the indigenous short-beaked echidna (Tachyglossus aculeatus) and the exotic European rabbit (Oryctolagus cuniculus), and surface and subsurface soils along a gradient in grazing-induced disturbance in an arid woodland. Microbial community composition varied little across the disturbance gradient, but there were substantial differences among the four microsites. Echidna pits supported a lower relative abundance of Acidobacteria and Cyanobacteria, but a higher relative abundance of Proteobacteria than rabbit pits and surface microsites. Moreover, these microsite differences varied with disturbance. Rabbit pits had a similar profile to the subsoil or the surface soils under moderate and high, but not low disturbance. Overall, echidna foraging pits had the greatest positive effect on function, assessed as mean enzyme concentrations, but rabbits had the least. The positive effects of echidna foraging on function were indirectly driven via microbial community composition. In particular, increasing activity was positively associated with increasing relative abundance of Proteobacteria, but decreasing Acidobacteria. Our study suggests that soil disturbance by animals may offset, to some degree, the oft-reported negative effects of grazing-induced disturbance on soil function. Further, our results suggest that most of this effect will be derived from echidnas, with little positive effects due to rabbits. Activities that enhance the habitat for echidnas or reduce rabbit populations are likely to have a positive effect on soil function in these systems. © 2016 The Authors. Journal of Animal Ecology © 2016 British Ecological Society.

Common limbic and frontal-striatal disturbances in patients with obsessive compulsive disorder, panic disorder and hypochondriasis.

PubMed

van den Heuvel, O A; Mataix-Cols, D; Zwitser, G; Cath, D C; van der Werf, Y D; Groenewegen, H J; van Balkom, A J L M; Veltman, D J

2011-11-01

Direct comparisons of brain function between obsessive compulsive disorder (OCD) and other anxiety or OCD spectrum disorders are rare. This study aimed to investigate the specificity of altered frontal-striatal and limbic activations during planning in OCD, a prototypical anxiety disorder (panic disorder) and a putative OCD spectrum disorder (hypochondriasis). The Tower of London task, a 'frontal-striatal' task, was used during functional magnetic resonance imaging measurements in 50 unmedicated patients, diagnosed with OCD (n=22), panic disorder (n=14) or hypochondriasis (n=14), and in 22 healthy subjects. Blood oxygen level-dependent (BOLD) signal changes were calculated for contrasts of interest (planning versus baseline and task load effects). Moreover, correlations between BOLD responses and both task performance and state anxiety were analysed. Overall, patients showed a decreased recruitment of the precuneus, caudate nucleus, globus pallidus and thalamus, compared with healthy controls. There were no statistically significant differences in brain activation between the three patient groups. State anxiety was negatively correlated with dorsal frontal-striatal activation. Task performance was positively correlated with dorsal frontal-striatal recruitment and negatively correlated with limbic and ventral frontal-striatal recruitment. Multiple regression models showed that adequate task performance was best explained by independent contributions from dorsolateral prefrontal cortex (positive correlation) and amygdala (negative correlation), even after controlling for state anxiety. Patients with OCD, panic disorder and hypochondriasis share similar alterations in frontal-striatal brain regions during a planning task, presumably partly related to increased limbic activation.

Sleep, Sleep Disorders, and Mild Traumatic Brain Injury. What We Know and What We Need to Know: Findings from a National Working Group.

PubMed

Wickwire, Emerson M; Williams, Scott G; Roth, Thomas; Capaldi, Vincent F; Jaffe, Michael; Moline, Margaret; Motamedi, Gholam K; Morgan, Gregory W; Mysliwiec, Vincent; Germain, Anne; Pazdan, Renee M; Ferziger, Reuven; Balkin, Thomas J; MacDonald, Margaret E; Macek, Thomas A; Yochelson, Michael R; Scharf, Steven M; Lettieri, Christopher J

2016-04-01

Disturbed sleep is one of the most common complaints following traumatic brain injury (TBI) and worsens morbidity and long-term sequelae. Further, sleep and TBI share neurophysiologic underpinnings with direct relevance to recovery from TBI. As such, disturbed sleep and clinical sleep disorders represent modifiable treatment targets to improve outcomes in TBI. This paper presents key findings from a national working group on sleep and TBI, with a specific focus on the testing and development of sleep-related therapeutic interventions for mild TBI (mTBI). First, mTBI and sleep physiology are briefly reviewed. Next, essential empirical and clinical questions and knowledge gaps are addressed. Finally, actionable recommendations are offered to guide active and efficient collaboration between academic, industry, and governmental stakeholders.

Programming Deep Brain Stimulation for Parkinson's Disease: The Toronto Western Hospital Algorithms.

PubMed

Picillo, Marina; Lozano, Andres M; Kou, Nancy; Puppi Munhoz, Renato; Fasano, Alfonso

2016-01-01

Deep brain stimulation (DBS) is an established and effective treatment for Parkinson's disease (PD). After surgery, a number of extensive programming sessions are performed to define the most optimal stimulation parameters. Programming sessions mainly rely only on neurologist's experience. As a result, patients often undergo inconsistent and inefficient stimulation changes, as well as unnecessary visits. We reviewed the literature on initial and follow-up DBS programming procedures and integrated our current practice at Toronto Western Hospital (TWH) to develop standardized DBS programming protocols. We propose four algorithms including the initial programming and specific algorithms tailored to symptoms experienced by patients following DBS: speech disturbances, stimulation-induced dyskinesia and gait impairment. We conducted a literature search of PubMed from inception to July 2014 with the keywords "deep brain stimulation", "festination", "freezing", "initial programming", "Parkinson's disease", "postural instability", "speech disturbances", and "stimulation induced dyskinesia". Seventy papers were considered for this review. Based on the literature review and our experience at TWH, we refined four algorithms for: (1) the initial programming stage, and management of symptoms following DBS, particularly addressing (2) speech disturbances, (3) stimulation-induced dyskinesia, and (4) gait impairment. We propose four algorithms tailored to an individualized approach to managing symptoms associated with DBS and disease progression in patients with PD. We encourage established as well as new DBS centers to test the clinical usefulness of these algorithms in supplementing the current standards of care. Copyright © 2016 Elsevier Inc. All rights reserved.

Targeting the Brain with a Neuroprotective Omega-3 Fatty Acid to Enhance Neurogenesis in Hypoxic Condition in Culture.

PubMed

Lo Van, Amanda; Sakayori, Nobuyuki; Hachem, Mayssa; Belkouch, Mounir; Picq, Madeleine; Fourmaux, Baptiste; Lagarde, Michel; Osumi, Noriko; Bernoud-Hubac, Nathalie

2018-06-01

Docosahexaenoic acid (DHA, 22:6n-3) is an essential omega-3 polyunsaturated fatty acid (PUFA) that is required for proper brain development and cerebral functions. While DHA deficiency in the brain was shown to be linked to the emergence of cerebral diseases, a dietary intake of omega-3 PUFA could prevent or attenuate neurologic disturbances linked with aging or neurodegenerative diseases. In this context, targeting the brain with DHA might offer great promise in developing new therapeutics for neurodegenerative diseases. We previously synthesized a stabilized form of DHA-containing lysophosphatidylcholine a major vector of DHA transportation to the brain, which is 1-acetyl,2-docoshexaenoyl-glycerophosphocholine, named AceDoPC®. Injection of AceDoPC® or DHA after experimental ischemic stroke showed that both molecules had neuroprotective effects but AceDoPC® was the most potent. This study aims to investigate the beneficial effects of DHA either unesterified or esterified within AceDoPC® on a model of neurogenesis in vitro, under physiological or pathological conditions. The effect of protectin DX (PDX, a double lipoxygenase product of DHA) was also tested. We cultured neural stem progenitor cells (NSPCs) derived from the adult mouse brain under normal or hypoxigenic (ischemic) conditions in vitro. Neurogenesis study of cell cultures with AceDoPC® showed enhanced neurogenesis compared to addition of unesterified DHA, PDX, or vehicle control, especially under pathological conditions. Our studies of the potential mechanisms involved in neuroprotection hinted that AceDoPC® neuroprotective and regenerative effects might be due in part to its anti-oxidative effects. These results indicate the potential for novel therapeutics against stroke that target the brain.

Reversible brain atrophy and cognitive impairment in an adolescent Japanese patient with primary adrenal Cushing's syndrome.

PubMed

Ohara, Nobumasa; Suzuki, Hiroshi; Suzuki, Akiko; Kaneko, Masanori; Ishizawa, Masahiro; Furukawa, Kazuo; Abe, Takahiro; Matsubayashi, Yasuhiro; Yamada, Takaho; Hanyu, Osamu; Shimohata, Takayoshi; Sone, Hirohito

2014-01-01

Endogenous Cushing's syndrome is an endocrine disease resulting from chronic exposure to excessive glucocorticoids produced in the adrenal cortex. Although the ultimate outcome remains uncertain, functional and morphological brain changes are not uncommon in patients with this syndrome, and generally persist even after resolution of hypercortisolemia. We present an adolescent patient with Cushing's syndrome who exhibited cognitive impairment with brain atrophy. A 19-year-old Japanese male visited a local hospital following 5 days of behavioral abnormalities, such as money wasting or nighttime wandering. He had hypertension and a 1-year history of a rounded face. Magnetic resonance imaging (MRI) revealed apparently diffuse brain atrophy. Because of high random plasma cortisol levels (28.7 μg/dL) at 10 AM, he was referred to our hospital in August 2011. Endocrinological testing showed adrenocorticotropic hormone-independent hypercortisolemia, and abdominal computed tomography demonstrated a 2.7 cm tumor in the left adrenal gland. The patient underwent left adrenalectomy in September 2011, and the diagnosis of cortisol-secreting adenoma was confirmed histologically. His hypertension and Cushingoid features regressed. Behavioral abnormalities were no longer observed, and he was classified as cured of his cognitive disturbance caused by Cushing's syndrome in February 2012. MRI performed 8 months after surgery revealed reversal of brain atrophy, and his subsequent course has been uneventful. In summary, the young age at onset and the short duration of Cushing's syndrome probably contributed to the rapid recovery of both cognitive dysfunction and brain atrophy in our patient. Cushing's syndrome should be considered as a possible etiological factor in patients with cognitive impairment and brain atrophy that is atypical for their age.

Assessing Brain–Muscle Connectivity in Human Locomotion through Mobile Brain/Body Imaging: Opportunities, Pitfalls, and Future Directions

PubMed Central

Gennaro, Federico; de Bruin, Eling D.

2018-01-01

Assessment of the cortical role during bipedalism has been a methodological challenge. While surface electroencephalography (EEG) is capable of non-invasively measuring cortical activity during human locomotion, it is associated with movement artifacts obscuring cerebral sources of activity. Recently, statistical methods based on blind source separation revealed potential for resolving this issue, by segregating non-cerebral/artifactual from cerebral sources of activity. This step marked a new opportunity for the investigation of the brains’ role while moving and was tagged mobile brain/body imaging (MoBI). This methodology involves simultaneous mobile recording of brain activity with several other body behavioral variables (e.g., muscle activity and kinematics), through wireless recording wearable devices/sensors. Notably, several MoBI studies using EEG–EMG approaches recently showed that the brain is functionally connected to the muscles and active throughout the whole gait cycle and, thus, rejecting the long-lasting idea of a solely spinal-driven bipedalism. However, MoBI and brain/muscle connectivity assessments during human locomotion are still in their fledgling state of investigation. Mobile brain/body imaging approaches hint toward promising opportunities; however, there are some remaining pitfalls that need to be resolved before considering their routine clinical use. This article discusses several of these pitfalls and proposes research to address them. Examples relate to the validity, reliability, and reproducibility of this method in ecologically valid scenarios and in different populations. Furthermore, whether brain/muscle connectivity within the MoBI framework represents a potential biomarker in neuromuscular syndromes where gait disturbances are evident (e.g., age-related sarcopenia) remains to be determined. PMID:29535995

Consistency of effects of tropical-forest disturbance on species composition and richness relative to use of indicator taxa.

PubMed

Stork, N E; Srivastava, D S; Eggleton, P; Hodda, M; Lawson, G; Leakey, R R B; Watt, A D

2017-08-01

Lawton et al. (1998) found, in a highly cited study, that the species richness of 8 taxa each responds differently to anthropogenic disturbance in Cameroon forests. Recent developments in conservation science suggest that net number of species is an insensitive measure of change and that understanding which species are affected by disturbance is more important. It is also recognized that all disturbance types are not equal in their effect on species and that grouping species according to function rather than taxonomy is more informative of responses of biodiversity to change. In a reanalysis of most of the original Cameroon data set (canopy and ground ants, termites, canopy beetles, nematodes, and butterflies), we focused on changes in species and functional composition rather than richness and used a more inclusive measure of forest disturbance based on 4 component drivers of change: years since disturbance, tree cover, soil compaction, and degree of tree removal. Effects of disturbance on compositional change were largely concordant between taxa. Contrary to Lawton et al.'s findings, species richness for most groups did not decline with disturbance level, providing support for the view that trends in species richness at local scales do not reflect the resilience of ecosystems to disturbance. Disturbance affected species composition more strongly than species richness for butterflies, canopy beetles, and litter ants. For these groups, disturbance caused species replacements rather than just species loss. Only termites showed effects of disturbance on species richness but not composition, indicating species loss without replacement. Although disturbance generally caused changes in composition, the strength of this relationship depended on the disturbance driver. Butterflies, litter ants, and nematodes were correlated with amount of tree cover, canopy beetles were most strongly correlated with time since disturbance, and termites were most strongly correlated with degree of soil disturbance. There were moderately divergent responses to disturbance between functional feeding groups. Disturbance was most strongly correlated with compositional differences of herbivores within beetles and nematodes and humus feeders within termites. Our results suggest that consideration of the impact of different forms of disturbance on species and functional composition, rather than on net numbers of species, is important when assessing the impacts of disturbance on biodiversity. © 2016 Society for Conservation Biology.

Chronic psychological effects of exposure to mercury vapour among chlorine-alkali plant workers.

PubMed

Pranjić, N; Sinanović, O; Jakubović, R

2003-01-01

Quantitative assessment of nervous system function is essential in characterising the nature and extent of impairment in individuals experiencing symptoms following work-place mercury vapour exposure. The purpose of this study was the application of standardised tests of behavioural, psychomotor and memory function to understand the neuropsychological effects of mercury in occupationally exposed chlorine-alkali plant workers. The study comprised 45 workers at a chlorine-alkali plant with the mean age of 39.36 +/- 5.94 years, who had been exposed to daily inhalation of mercury vapour over long-term employment of 16.06 +/- 4.29 years. The cumulative mercury index was 155.32 +/- 95.02 micrograms/g creatinine, the mean of urinary mercury concentrations on the first day of the study was 119.50 +/- 157.24 micrograms/g creatinine, and the mean of urinary mercury concentrations 120 days after cessation of exposure was 21.70 +/- 26.07 micrograms/g creatinine. The analysis included tests of behavioural, psychomotor and memory function. The behavioural test battery consisted of: Environmental Worry Scale (EWS), Minnesota Modified Personal Inventory (MMPI-2), Purdue standard 25 minute test, and adapted, 10 minutes test, Bender's Visual-Motor Gestalt test (BGT), and Eysenck Personality Inventory (EPQ). The data were compared to a control group of 32 not directly exposed workers. In the mercury vapour exposed workers with relatively high level exposure to inorganic mercury vapour (TWA/TLV = 0.12 mg/m3/0.025 mg/m3) we identified somatic depression-hypochondria symptoms with higher scores for scales: hysteria (P < 0.001), schizoid and psycho-asthenia (MMPI-2). The mercury-exposed workers had introvert behaviour (EPQ, MMPI-2). The cognitive disturbances in mercury-exposed workers were identified as: concentration difficulty, psychomotor, perceptual and motor coordination disturbances, and brain effects. We identified fine tremor of the hands in 34 out of 45 mercury-exposed workers (BGT). The results point to a relationship between the duration of mercury exposure and the long-term, probably irreversible, psychological disturbances.

Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage

PubMed Central

Sun, Kai; Fan, Jingyu; Han, Jingyan

2015-01-01

Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage. PMID:26579420

Intraoperative mapping of language functions: a longitudinal neurolinguistic analysis.

PubMed

Ilmberger, Josef; Ruge, Maximilian; Kreth, Friedrich-Wilhelm; Briegel, Josef; Reulen, Hans-Juergen; Tonn, Joerg-Christian

2008-10-01

This prospective longitudinally designed study was conducted to evaluate language functions pre- and postoperatively in patients who underwent microsurgical treatment of tumors in close proximity to or within language areas and to detect those patients at risk for a postoperative aphasic disturbance. Between 1991 and 2005, 153 awake craniotomies with subsequent cortical mapping of language functions were performed in 149 patients. Language functions were assessed using a standardized test battery. Risk factors were obtained from multivariate logistic regression models. Language mapping was able to be performed in all patients, and complete tumor resection was achieved in 48.4%. Within 21 days after surgery a new language deficit (aphasic disturbance) was observed in 41 (32%) of the 128 cases without preoperative deficits. There were a total of 60 cases involving postoperative aphasic disturbances, including cases both with and without preoperative disturbances. Risk factors for postoperative aphasic disturbance were preoperative aphasia (p<0.0002), intraoperative complications (p<0.02), language-positive sites within the tumor (p<0.001), and nonfrontal lesion location (p<0.001). In patients without a preoperative deficit, a normal (yet submaximal) naming performance was a powerful predictor for an early postoperative aphasic disturbance (p<0.0003). Seven months after treatment 10.9% of the 128 cases without preoperative aphasic disturbances continued to demonstrate new postoperative language disturbances. A total of 17.6% of all cases demonstrated new postoperative language disturbances after 7 months. Risk factors for persistent aphasic disturbance were increased age (>40 years, p<0.02) and preoperative aphasia (p<0.001). Every attempt should be undertaken to preserve language-relevant areas intraoperatively, even when they are located within the tumor. New postoperative deficits resolve in the majority of patients, which may be a result of cortical mapping as well as functional reorganization.

Approaching a network connectivity-driven classification of the psychosis continuum: a selective review and suggestions for future research.

PubMed

Schmidt, André; Diwadkar, Vaibhav A; Smieskova, Renata; Harrisberger, Fabienne; Lang, Undine E; McGuire, Philip; Fusar-Poli, Paolo; Borgwardt, Stefan

2014-01-01

Brain changes in schizophrenia evolve along a dynamic trajectory, emerging before disease onset and proceeding with ongoing illness. Recent investigations have focused attention on functional brain interactions, with experimental imaging studies supporting the disconnection hypothesis of schizophrenia. These studies have revealed a broad spectrum of abnormalities in brain connectivity in patients, particularly for connections integrating the frontal cortex. A critical point is that brain connectivity abnormalities, including altered resting state connectivity within the fronto-parietal (FP) network, are already observed in non-help-seeking individuals with psychotic-like experiences. If we consider psychosis as a continuum, with individuals with psychotic-like experiences at the lower and psychotic patients at the upper ends, individuals with psychotic-like experiences represent a key population for investigating the validity of putative biomarkers underlying the onset of psychosis. This paper selectively addresses the role played by FP connectivity in the psychosis continuum, which includes patients with chronic psychosis, early psychosis, clinical high risk, genetic high risk, as well as the general population with psychotic experiences. We first discuss structural connectivity changes among the FP pathway in each domain in the psychosis continuum. This may provide a basis for us to gain an understanding of the subsequent changes in functional FP connectivity. We further indicate that abnormal FP connectivity may arise from glutamatergic disturbances of this pathway, in particular from abnormal NMDA receptor-mediated plasticity. In the second part of this paper we propose some concepts for further research on the use of network connectivity in the classification of the psychosis continuum. These concepts are consistent with recent efforts to enhance the role of data in driving the diagnosis of psychiatric spectrum diseases.

An uncommon case of random fire-setting behavior associated with Todd paralysis: a case report.

PubMed

Kanehisa, Masayuki; Morinaga, Katsuhiko; Kohno, Hisae; Maruyama, Yoshihiro; Ninomiya, Taiga; Ishitobi, Yoshinobu; Tanaka, Yoshihiro; Tsuru, Jusen; Hanada, Hiroaki; Yoshikawa, Tomoya; Akiyoshi, Jotaro

2012-08-31

The association between fire-setting behavior and psychiatric or medical disorders remains poorly understood. Although a link between fire-setting behavior and various organic brain disorders has been established, associations between fire setting and focal brain lesions have not yet been reported. Here, we describe the case of a 24-year-old first time arsonist who suffered Todd's paralysis prior to the onset of a bizarre and random fire-setting behavior. A case of a 24-year-old man with a sudden onset of a bizarre and random fire-setting behavior is reported. The man, who had been arrested on felony arson charges, complained of difficulties concentrating and of recent memory disturbances with leg weakness. A video-EEG recording demonstrated a close relationship between the focal motor impairment and a clear-cut epileptic ictal discharge involving the bilateral motor cortical areas. The SPECT result was statistically analyzed by comparing with standard SPECT images obtained from our institute (easy Z-score imaging system; eZIS). eZIS revealed hypoperfusion in cingulate cortex, basal ganglia and hyperperfusion in frontal cortex,. A neuropsychological test battery revealed lower than normal scores for executive function, attention, and memory, consistent with frontal lobe dysfunction. The fire-setting behavior and Todd's paralysis, together with an unremarkable performance on tests measuring executive function fifteen months prior, suggested a causal relationship between this organic brain lesion and the fire-setting behavior. The case describes a rare and as yet unreported association between random, impulse-driven fire-setting behavior and damage to the brain and suggests a disconnection of frontal lobe structures as a possible pathogenic mechanism.

Approaching a network connectivity-driven classification of the psychosis continuum: a selective review and suggestions for future research

PubMed Central

Schmidt, André; Diwadkar, Vaibhav A.; Smieskova, Renata; Harrisberger, Fabienne; Lang, Undine E.; McGuire, Philip; Fusar-Poli, Paolo; Borgwardt, Stefan

2015-01-01

Brain changes in schizophrenia evolve along a dynamic trajectory, emerging before disease onset and proceeding with ongoing illness. Recent investigations have focused attention on functional brain interactions, with experimental imaging studies supporting the disconnection hypothesis of schizophrenia. These studies have revealed a broad spectrum of abnormalities in brain connectivity in patients, particularly for connections integrating the frontal cortex. A critical point is that brain connectivity abnormalities, including altered resting state connectivity within the fronto-parietal (FP) network, are already observed in non-help-seeking individuals with psychotic-like experiences. If we consider psychosis as a continuum, with individuals with psychotic-like experiences at the lower and psychotic patients at the upper ends, individuals with psychotic-like experiences represent a key population for investigating the validity of putative biomarkers underlying the onset of psychosis. This paper selectively addresses the role played by FP connectivity in the psychosis continuum, which includes patients with chronic psychosis, early psychosis, clinical high risk, genetic high risk, as well as the general population with psychotic experiences. We first discuss structural connectivity changes among the FP pathway in each domain in the psychosis continuum. This may provide a basis for us to gain an understanding of the subsequent changes in functional FP connectivity. We further indicate that abnormal FP connectivity may arise from glutamatergic disturbances of this pathway, in particular from abnormal NMDA receptor-mediated plasticity. In the second part of this paper we propose some concepts for further research on the use of network connectivity in the classification of the psychosis continuum. These concepts are consistent with recent efforts to enhance the role of data in driving the diagnosis of psychiatric spectrum diseases. PMID:25628553

Thyroid hormones states and brain development interactions.

PubMed

Ahmed, Osama M; El-Gareib, A W; El-Bakry, A M; Abd El-Tawab, S M; Ahmed, R G

2008-04-01

The action of thyroid hormones (THs) in the brain is strictly regulated, since these hormones play a crucial role in the development and physiological functioning of the central nervous system (CNS). Disorders of the thyroid gland are among the most common endocrine maladies. Therefore, the objective of this study was to identify in broad terms the interactions between thyroid hormone states or actions and brain development. THs regulate the neuronal cytoarchitecture, neuronal growth and synaptogenesis, and their receptors are widely distributed in the CNS. Any deficiency or increase of them (hypo- or hyperthyroidism) during these periods may result in an irreversible impairment, morphological and cytoarchitecture abnormalities, disorganization, maldevelopment and physical retardation. This includes abnormal neuronal proliferation, migration, decreased dendritic densities and dendritic arborizations. This drastic effect may be responsible for the loss of neurons vital functions and may lead, in turn, to the biochemical dysfunctions. This could explain the physiological and behavioral changes observed in the animals or human during thyroid dysfunction. It can be hypothesized that the sensitive to the thyroid hormones is not only remarked in the neonatal period but also prior to birth, and THs change during the development may lead to the brain damage if not corrected shortly after the birth. Thus, the hypothesis that neurodevelopmental abnormalities might be related to the thyroid hormones is plausible. Taken together, the alterations of neurotransmitters and disturbance in the GABA, adenosine and pro/antioxidant systems in CNS due to the thyroid dysfunction may retard the neurogenesis and CNS growth and the reverse is true. In general, THs disorder during early life may lead to distortions rather than synchronized shifts in the relative development of several central transmitter systems that leads to a multitude of irreversible morphological and biochemical abnormalities (pathophysiology). Thus, further studies need to be done to emphasize this concept.

Low-frequency connectivity is associated with mild traumatic brain injury.

PubMed

Dunkley, B T; Da Costa, L; Bethune, A; Jetly, R; Pang, E W; Taylor, M J; Doesburg, S M

2015-01-01

Mild traumatic brain injury (mTBI) occurs from a closed-head impact. Often referred to as concussion, about 20% of cases complain of secondary psychological sequelae, such as disorders of attention and memory. Known as post-concussive symptoms (PCS), these problems can severely disrupt the patient's quality of life. Changes in local spectral power, particularly low-frequency amplitude increases and/or peak alpha slowing have been reported in mTBI, but large-scale connectivity metrics based on inter-regional amplitude correlations relevant for integration and segregation in functional brain networks, and their association with disorders in cognition and behaviour, remain relatively unexplored. Here, we used non-invasive neuroimaging with magnetoencephalography to examine functional connectivity in a resting-state protocol in a group with mTBI (n = 20), and a control group (n = 21). We observed a trend for atypical slow-wave power changes in subcortical, temporal and parietal regions in mTBI, as well as significant long-range increases in amplitude envelope correlations among deep-source, temporal, and frontal regions in the delta, theta, and alpha bands. Subsequently, we conducted an exploratory analysis of patterns of connectivity most associated with variability in secondary symptoms of mTBI, including inattention, anxiety, and depression. Differential patterns of altered resting state neurophysiological network connectivity were found across frequency bands. This indicated that multiple network and frequency specific alterations in large scale brain connectivity may contribute to overlapping cognitive sequelae in mTBI. In conclusion, we show that local spectral power content can be supplemented with measures of correlations in amplitude to define general networks that are atypical in mTBI, and suggest that certain cognitive difficulties are mediated by disturbances in a variety of alterations in network interactions which are differentially expressed across canonical neurophysiological frequency ranges.

Functional significance of the electrocorticographic auditory responses in the premotor cortex.

PubMed

Tanji, Kazuyo; Sakurada, Kaori; Funiu, Hayato; Matsuda, Kenichiro; Kayama, Takamasa; Ito, Sayuri; Suzuki, Kyoko

2015-01-01

Other than well-known motor activities in the precentral gyrus, functional magnetic resonance imaging (fMRI) studies have found that the ventral part of the precentral gyrus is activated in response to linguistic auditory stimuli. It has been proposed that the premotor cortex in the precentral gyrus is responsible for the comprehension of speech, but the precise function of this area is still debated because patients with frontal lesions that include the precentral gyrus do not exhibit disturbances in speech comprehension. We report on a patient who underwent resection of the tumor in the precentral gyrus with electrocorticographic recordings while she performed the verb generation task during awake brain craniotomy. Consistent with previous fMRI studies, high-gamma band auditory activity was observed in the precentral gyrus. Due to the location of the tumor, the patient underwent resection of the auditory responsive precentral area which resulted in the post-operative expression of a characteristic articulatory disturbance known as apraxia of speech (AOS). The language function of the patient was otherwise preserved and she exhibited intact comprehension of both spoken and written language. The present findings demonstrated that a lesion restricted to the ventral precentral gyrus is sufficient for the expression of AOS and suggest that the auditory-responsive area plays an important role in the execution of fluent speech rather than the comprehension of speech. These findings also confirm that the function of the premotor area is predominantly motor in nature and its sensory responses is more consistent with the "sensory theory of speech production," in which it was proposed that sensory representations are used to guide motor-articulatory processes.

Neural networks related to dysfunctional face processing in autism spectrum disorder

PubMed Central

Nickl-Jockschat, Thomas; Rottschy, Claudia; Thommes, Johanna; Schneider, Frank; Laird, Angela R.; Fox, Peter T.; Eickhoff, Simon B.

2016-01-01

One of the most consistent neuropsychological findings in autism spectrum disorders (ASD) is a reduced interest in and impaired processing of human faces. We conducted an activation likelihood estimation meta-analysis on 14 functional imaging studies on neural correlates of face processing enrolling a total of 164 ASD patients. Subsequently, normative whole-brain functional connectivity maps for the identified regions of significant convergence were computed for the task-independent (resting-state) and task-dependent (co-activations) state in healthy subjects. Quantitative functional decoding was performed by reference to the BrainMap database. Finally, we examined the overlap of the delineated network with the results of a previous meta-analysis on structural abnormalities in ASD as well as with brain regions involved in human action observation/imitation. We found a single cluster in the left fusiform gyrus showing significantly reduced activation during face processing in ASD across all studies. Both task-dependent and task-independent analyses indicated significant functional connectivity of this region with the temporo-occipital and lateral occipital cortex, the inferior frontal and parietal cortices, the thalamus and the amygdala. Quantitative reverse inference then indicated an association of these regions mainly with face processing, affective processing, and language-related tasks. Moreover, we found that the cortex in the region of right area V5 displaying structural changes in ASD patients showed consistent connectivity with the region showing aberrant responses in the context of face processing. Finally, this network was also implicated in the human action observation/imitation network. In summary, our findings thus suggest a functionally and structurally disturbed network of occipital regions related primarily to face (but potentially also language) processing, which interact with inferior frontal as well as limbic regions and may be the core of aberrant face processing and reduced interest in faces in ASD. PMID:24869925

Functional Resistance to Recurrent Spatially Heterogeneous Disturbances Is Facilitated by Increased Activity of Surviving Bacteria in a Virtual Ecosystem

PubMed Central

König, Sara; Worrich, Anja; Banitz, Thomas; Harms, Hauke; Kästner, Matthias; Miltner, Anja; Wick, Lukas Y.; Frank, Karin; Thullner, Martin; Centler, Florian

2018-01-01

Bacterial degradation of organic compounds is an important ecosystem function with relevance to, e.g., the cycling of elements or the degradation of organic contaminants. It remains an open question, however, to which extent ecosystems are able to maintain such biodegradation function under recurrent disturbances (functional resistance) and how this is related to the bacterial biomass abundance. In this paper, we use a numerical simulation approach to systematically analyze the dynamic response of a microbial population to recurrent disturbances of different spatial distribution. The spatially explicit model considers microbial degradation, growth, dispersal, and spatial networks that facilitate bacterial dispersal mimicking effects of mycelial networks in nature. We find: (i) There is a certain capacity for high resistance of biodegradation performance to recurrent disturbances. (ii) If this resistance capacity is exceeded, spatial zones of different biodegradation performance develop, ranging from no or reduced to even increased performance. (iii) Bacterial biomass and biodegradation dynamics respond inversely to the spatial fragmentation of disturbances: overall biodegradation performance improves with increasing fragmentation, but bacterial biomass declines. (iv) Bacterial dispersal networks can enhance functional resistance against recurrent disturbances, mainly by reactivating zones in the core of disturbed areas, even though this leads to an overall reduction of bacterial biomass. PMID:29696013

[Artificial Inversion of the Left-Right Visceral Asymmetry in Vertebrates: Conceptual Approaches and Experimental Solutions].

PubMed

Truleva, A S; Malashichev, E B; Ermakov, A S

2015-01-01

Externally, vertebrates are bilaterally symmetrical; however, left-right asymmetry is observed in the structure of their internal organs and systems of organs (circulatory, digestive, and respiratory). In addition to the asymmetry of internal organs (visceral), there is also functional (i.e., asymmetrical functioning of organs on the left and right sides of the body) and behavioral asymmetry. The question of a possible association between different types of asymmetry is still open. The study of the mechanisms of such association, in addition to the fundamental interest, has important applications for biomedicine, primarily for the understanding of the brain functioning in health and disease and for the development of methods of treatment of certain mental diseases, such as schizophrenia and autism, for which the disturbance of left-right asymmetry of the brain was shown. To study the deep association between different types of asymmetry, it is necessary to obtain adequate animal models (primarily animals with inverted visceral organs, situs inversus totalis). There are two main possible approaches to obtaining such model organisms: mutagenesis followed by selection of mutant strains with mutations in the genes that affect the formation of the left-right visceral asymmetry and experimental obtaining of animals with inverted internal organs. This review focuses on the second approach. We describe the theoretical models for establishing left-right asymmetry and possible experimental approaches to obtaining animals with inverted internal organs.

Jet Engine Control Using Ethernet with a BRAIN (Postprint)

DTIC Science & Technology

2008-07-01

current communications may be mitigated. 15. SUBJECT TERMS BRAIN, Braided Ring Availability Integrity Network, Gas turbine, FADEC , disturbed...urrent state of the art engine controls have converged on the notion of the Full Authority Digital Engine Control ( FADEC ), which consists of a centralized...is completely dependent on the proper operation of the controller. In current systems, the FADEC is often located on the relatively cool engine fan

Chapter 8 Military Personnel With Traumatic Brain Injuries and Insomnia Have Reductions in PTSD and Improved Perceived Health Following Sleep Restoration: A Relationship Moderated by Inflammation.

PubMed

Barr, Taura; Livingston, Whitney; Guardado, Pedro; Baxter, Tristin; Mysliwiec, Vincent; Gill, Jessica

2015-01-01

Up to one-third of deployed military personnel sustain a traumatic brain injury (TBI). TBIs and the stress of deployment contribute to the vulnerability for chronic sleep disturbance, resulting in high rates of insomnia diagnoses as well as symptoms of posttraumatic stress disorder (PTSD), depression, and declines in health-related quality of life (HRQOL). Inflammation is associated with insomnia; however, the impact of sleep changes on comorbid symptoms and inflammation in this population is unknown. In this study, we examined the relationship between reported sleep changes and the provision of the standard of care, which could include one or more of the following: cognitive behavioral therapy (CBT), medications, and continuous positive airway pressure (CPAP). We compared the following: (a) the group with a decrease in the Pittsburgh Sleep Quality Index (PSQI; restorative sleep) and (b) the group with no change or increase in PSQI (no change). Independent t tests and chi-square tests were used to compare the groups on demographic and clinical characteristics, and mixed between-within subjects analysis of variance tests were used to determine the effect of group differences on changes in comorbid symptoms. Linear regression models were used to examine the role of inflammation in changes in symptoms and HRQOL. The sample included 70 recently deployed military personnel with TBI, seeking care for sleep disturbances. Thirty-seven participants reported restorative sleep and 33 reported no sleep changes or worse sleep. The two groups did not differ in demographic characteristics or clinical symptoms at baseline. The TBI+restored sleep group had significant reductions in PTSD and depression over the 3-month period, whereas the TBI+no change group had a slight increase in both PTSD and depression. The TBI+restored sleep group also had significant changes in HRQOL, including the following HRQOL subcomponents: physical functioning, role limitations in physical health, social functioning, emotional well-being, energy/fatigue, and general health perceptions. In a linear regression model using a forced entry method, the dependent variable of change in C-reactive protein (CRP) concentrations was significantly related to changes in PTSD symptoms and HRQOL in the TBI+restored sleep group, with R2=0.43, F33,3=8.31, p<.01. Military personnel with TBIs who have a reduction in insomnia symptoms following a standard-of-care treatment report less severe symptoms of depression and PTSD and improved HRQOL, which relate to decreased plasma concentrations of CRP. These findings suggest that treatment for sleep disturbances in this TBI+military population is associated with improvements in health and decreases in inflammation. The contributions of inflammation-induced changes in PTSD and depression in sleep disturbances in TBI + military personnel require further study.

A putative model of overeating and obesity based on brain-derived neurotrophic factor: direct and indirect effects.

PubMed

Ooi, Cara L; Kennedy, James L; Levitan, Robert D

2012-08-01

Increased food intake is a major contributor to the obesity epidemic in all age groups. Elucidating brain systems that drive overeating and that might serve as targets for novel prevention and treatment interventions is thus a high priority for obesity research. The authors consider 2 major pathways by which decreased activity of brain-derived neurotrophic factor (BDNF) may confer vulnerability to overeating and weight gain in an obesogenic environment. The first "direct" pathway focuses on the specific role of BDNF as a mediator of food intake control at brain areas rich in BDNF receptors, including the hypothalamus and hindbrain. It is proposed that low BDNF activity limited to this direct pathway may best explain overeating and obesity outside the context of major neuropsychiatric disturbance. A second "indirect" pathway considers the broad neurotrophic effects of BDNF on key monoamine systems that mediate mood dysregulation, impulsivity, and executive dysfunction as well as feeding behavior per se. Disruption in this pathway may best explain overeating and obesity in the context of various neuropsychiatric disturbances including mood disorders, attention-deficit disorder, and/or binge eating disorders. An integrative model that considers these potential roles of BDNF in promoting obesity is presented. The implications of this model for the early prevention and treatment of obesity are also considered.

Methyl group balance in brain and liver: role of choline on increased S-adenosyl methionine (SAM) demand by chronic arsenic exposure.

PubMed

Ríos, Rosalva; Santoyo, Martha E; Cruz, Daniela; Delgado, Juan Manuel; Zarazúa, Sergio; Jiménez-Capdeville, María E

2012-11-30

Arsenic toxicity has been related to its interference with one carbon metabolism, where a high demand of S-adenosylmethionine (SAM) for arsenic methylation as well as a failure of its regeneration would compromise the availability of methyl groups for diverse cellular functions. Since exposed animals show disturbances of methylated products such as methylated arginines, myelin and axon membranes, this work investigates whether alterations of SAM, choline and phosphatidylcholine (PC) in the brain of arsenic exposed rats are associated with myelin alterations and myelin basic protein (MBP) immunoreactivity. Also these metabolites, morphologic and biochemical markers of methyl group alterations were analyzed in the liver, the main site of arsenic methylation. In adult, life-long arsenic exposed rats through drinking water (3 ppm), no changes of SAM, choline and PC concentrations where found in the brain, but SAM and PC were severely decreased in liver accompanied by a significant increase of choline. These results suggest that choline plays an important role as methyl donor in arsenic exposure, which could underlie hepatic affections observed when arsenic exposure is combined with other environmental factors. Also, important myelin and nerve fiber alterations, accompanied by a 75% decrease of MBP immunoreactivity were not associated with a SAM deficit in the brain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The nature and treatment of stuttering as revealed by fMRI A within- and between-group comparison.

PubMed

Neumann, Katrin; Euler, Harald A; von Gudenberg, Alexander Wolff; Giraud, Anne-Lise; Lanfermann, Heinrich; Gall, Volker; Preibisch, Christine

2003-01-01

This article reviews some of our recent functional magnetic resonance imaging (fMRI) studies of stuttering. Using event-related fMRI experiments, we investigated brain activation during speech production. Results of three studies comparing persons who stutter (PWS) and persons who do not stutter (PWNS) are outlined. Their findings point to a region in the right frontal operculum (RFO) that was consistently implicated in stuttering. During overt reading and before fluency shaping therapy, PWS showed higher and more distributed neuronal activation than PWNS. Immediately after therapy differential activations were even more distributed and left sided. They extended to frontal, temporal, and parietal regions, anterior cingulate, insula, and putamen. These over-activations were slightly reduced and again more right sided two years after therapy. Left frontal deactivations remained stable over two years of observation, and therefore possibly indicate a dysfunction. After therapy, we noted higher activations in persons who stutter moderately than in those who stutter severely. These activations might reflect patterns of compensation. We discuss why these findings suggest that fluency-inducing techniques might synchronize a disturbed signal transmission between auditory, speech motor planning, and motor areas. The reader will learn about and be able to: (1) identify regions of brain activations and deactivations specific for PWS; (2) describe brain activation changes induced by fluency shaping therapy; and (3) discuss the correlation between stuttering severity and brain activation.

Do Quercus ilex woodlands undergo abrupt non-linear functional changes in response to human disturbance along a climatic gradient?

NASA Astrophysics Data System (ADS)

Bochet, Esther; García-Fayos, Patricio; José Molina, Maria; Moreno de las Heras, Mariano; Espigares, Tíscar; Nicolau, Jose Manuel; Monleon, Vicente

2017-04-01

Theoretical models predict that drylands are particularly prone to suffer critical transitions with abrupt non-linear changes in their structure and functions as a result of the existing complex interactions between climatic fluctuations and human disturbances. However, so far, few studies provide empirical data to validate these models. We aim at determining how holm oak (Quercus ilex) woodlands undergo changes in their functions in response to human disturbance along an aridity gradient (from semi-arid to sub-humid conditions), in eastern Spain. For that purpose, we used (a) remote-sensing estimations of precipitation-use-efficiency (PUE) from enhanced vegetation index (EVI) observations performed in 231x231 m plots of the Moderate Resolution Imaging Spectroradiometer (MODIS); (b) biological and chemical soil parameter determinations (extracellular soil enzyme activity, soil respiration, nutrient cycling processes) from soil sampled in the same plots; (c) vegetation parameter determinations (ratio of functional groups) from vegetation surveys performed in the same plots. We analyzed and compared the shape of the functional change (in terms of PUE and soil and vegetation parameters) in response to human disturbance intensity for our holm oak sites along the aridity gradient. Overall, our results evidenced important differences in the shape of the functional change in response to human disturbance between climatic conditions. Semi-arid areas experienced a more accelerated non-linear decrease with an increasing disturbance intensity than sub-humid ones. The proportion of functional groups (herbaceous vs. woody cover) played a relevant role in the shape of the functional response of the holm oak sites to human disturbance.