Modulatory Effects of Dietary Amino Acids on Neurodegenerative Diseases.

PubMed

Rajagopal, Senthilkumar; Sangam, Supraj Raja; Singh, Shubham; Joginapally, Venkateswara Rao

2016-01-01

Proteins are playing a vital role in maintaining the cellular integrity and function, as well as for brain cells. Protein intake and supplementation of individual amino acids can affect the brain functioning and mental health, and many of the neurotransmitters in the brain are made from amino acids. The amino acid supplementation has been found to reduce symptoms, as they are converted into neurotransmitters which in turn extenuate the mental disorders. The biosynthesis of amino acids in the brain is regulated by the concentration of amino acids in plasma. The brain diseases such as depression, bipolar disorder, schizophrenia, obsessive-compulsive disorder (OCD), and Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD) are the most common mental disorders that are currently widespread in numerous countries. The intricate biochemical and molecular machinery contributing to the neurological disorders is still unknown, and in this chapter, we revealed the involvement of dietary amino acids on neurological diseases.

Distinctions between organic brain syndrome and functional psychiatric disorders: based on the geriatric mental state interview.

PubMed

Fleiss, J; Gurland, B; Roche, P D

1976-01-01

Discriminant function analysis was employed to study the ability of the Geriatric Mental Status interview to distinguish between patients diagnosed by the project as having an organic brain syndrome or a functional psychiatric disorder. In both New York and London, patients with organic brain syndrome scored significantly higher (p less than 0.05) than those with functional disorders on the factors of impaired memory, disorientation and incomprehensibility and significantly lower on the factors of depression and somatic concerns. Discriminant functions calculated from data on the New York and London patients separately significantly distinguished not only the patients on whom the functions were based but the patients in the other sample as well.

The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study.

PubMed

Samaras, Katherine; Lutgers, Helen L; Kochan, Nicole A; Crawford, John D; Campbell, Lesley V; Wen, Wei; Slavin, Melissa J; Baune, Bernard T; Lipnicki, Darren M; Brodaty, Henry; Trollor, Julian N; Sachdev, Perminder S

2014-04-01

Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volumes by magnetic resonance imaging (n = 312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0 ± 4.2 vs. 46.7 ± 5.7 mm(3) vs. 18.1 ± 6.2, respectively, p < 0.005). Stable IFG did not show greater decline in global cognition or brain volumes compared to normal. Incident glucose disorders, like diabetes, are associated with accelerated decline in global cognition and brain volumes in non-demented elderly, whereas stable IFG is not. Preventing deterioration in glucose metabolism in the elderly may help preserve brain structure and function.

[Brain imaging in autism spectrum disorders. A review].

PubMed

Dziobek, I; Köhne, S

2011-05-01

In the past two decades, an increasing number of functional and structural brain imaging studies has provided insights into the neurobiological basis of autism spectrum disorders (ASD). This article summarizes pertinent functional brain imaging studies addressing the neuronal underpinnings of ASD symptomatology (impairments in social interaction and communication, repetitive and restrictive behavior) and associated neuropsychological deficits (theory of mind, executive functions, central coherence), complemented by relevant structural imaging findings. The results of these studies show that although cognitive functions in ASD are generally mediated by the same brain regions as in typically developed individuals, the degree and especially the patterns of brain activation often differ. Therefore, a hypothesis of aberrant network connectivity has increasingly been favored over one of focal brain dysfunction.

Swallowing Disorders in Severe Brain Injury in the Arousal Phase.

PubMed

Bremare, A; Rapin, A; Veber, B; Beuret-Blanquart, F; Verin, E

2016-08-01

The objective of this study was to determine the clinical characteristics of swallowing disorders in severe brain injury in the arousal phase after coma. Between December 1, 2013 and June 30, 2014, eleven patients with severe acquired brain injury who were admitted to rehabilitation center (Male 81.8 %; 40.7 ± 14.6 years) were included in the study. Evaluation of swallowing included a functional examination, clinical functional swallowing test, and naso-endoscopic swallowing test. All patients had swallowing disorders at admission. The first functional swallowing test showed oral (77.8 %) and pharyngeal (66.7 %) food bolus transport disorders; and alterations in airway protection mechanisms (80 %). Swallowing test under endoscopic control showed a disorder in swallowing coordination in 55.6 % of patients tested. Seven (63.6 %) patients resumed oral feeding within an average of 6 weeks after admission to rehabilitation center and 14 weeks after acquired brain injury. Six (85.7 %) of these seven patients continued to require modified solid and liquid textures. Swallowing disorders are a major concern in severe brain injury in the arousal phase. Early bedside assessment of swallowing is essential for detection of swallowing disorders to propose appropriate medical rehabilitation care to these patients in a state of altered consciousness.

The protocadherin 17 gene affects cognition, personality, amygdala structure and function, synapse development and risk of major mood disorders.

PubMed

Chang, H; Hoshina, N; Zhang, C; Ma, Y; Cao, H; Wang, Y; Wu, D-D; Bergen, S E; Landén, M; Hultman, C M; Preisig, M; Kutalik, Z; Castelao, E; Grigoroiu-Serbanescu, M; Forstner, A J; Strohmaier, J; Hecker, J; Schulze, T G; Müller-Myhsok, B; Reif, A; Mitchell, P B; Martin, N G; Schofield, P R; Cichon, S; Nöthen, M M; Walter, H; Erk, S; Heinz, A; Amin, N; van Duijn, C M; Meyer-Lindenberg, A; Tost, H; Xiao, X; Yamamoto, T; Rietschel, M; Li, M

2018-02-01

Major mood disorders, which primarily include bipolar disorder and major depressive disorder, are the leading cause of disability worldwide and pose a major challenge in identifying robust risk genes. Here, we present data from independent large-scale clinical data sets (including 29 557 cases and 32 056 controls) revealing brain expressed protocadherin 17 (PCDH17) as a susceptibility gene for major mood disorders. Single-nucleotide polymorphisms (SNPs) spanning the PCDH17 region are significantly associated with major mood disorders; subjects carrying the risk allele showed impaired cognitive abilities, increased vulnerable personality features, decreased amygdala volume and altered amygdala function as compared with non-carriers. The risk allele predicted higher transcriptional levels of PCDH17 mRNA in postmortem brain samples, which is consistent with increased gene expression in patients with bipolar disorder compared with healthy subjects. Further, overexpression of PCDH17 in primary cortical neurons revealed significantly decreased spine density and abnormal dendritic morphology compared with control groups, which again is consistent with the clinical observations of reduced numbers of dendritic spines in the brains of patients with major mood disorders. Given that synaptic spines are dynamic structures which regulate neuronal plasticity and have crucial roles in myriad brain functions, this study reveals a potential underlying biological mechanism of a novel risk gene for major mood disorders involved in synaptic function and related intermediate phenotypes.

Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naïve Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial

PubMed Central

Lin, Hsiang-Yuan

2016-01-01

Background: Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. Methods: After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18–52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. Results: At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. Conclusions: Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder. PMID:26377368

Atomoxetine Treatment Strengthens an Anti-Correlated Relationship between Functional Brain Networks in Medication-Naïve Adults with Attention-Deficit Hyperactivity Disorder: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

PubMed

Lin, Hsiang-Yuan; Gau, Susan Shur-Fen

2015-09-16

Although atomoxetine demonstrates efficacy in individuals with attention-deficit hyperactivity disorder, its treatment effects on brain resting-state functional connectivity remain unknown. Therefore, we aimed to investigate major brain functional networks in medication-naïve adults with attention-deficit hyperactivity disorder and the efficacy of atomoxetine treatment on resting-state functional connectivity. After collecting baseline resting-state functional MRI scans from 24 adults with attention-deficit hyperactivity disorder (aged 18-52 years) and 24 healthy controls (matched in demographic characteristics), the participants with attention-deficit hyperactivity disorder were randomly assigned to atomoxetine (n=12) and placebo (n=12) arms in an 8-week, double-blind, placebo-controlled trial. The primary outcome was functional connectivity assessed by a resting-state functional MRI. Seed-based functional connectivity was calculated and compared for the affective, attention, default, and cognitive control networks. At baseline, we found atypical cross talk between the default, cognitive control, and dorsal attention networks and hypoconnectivity within the dorsal attention and default networks in adults with attention-deficit hyperactivity disorder. Our first-ever placebo-controlled clinical trial incorporating resting-state functional MRI showed that treatment with atomoxetine strengthened an anticorrelated relationship between the default and task-positive networks and modulated all major brain networks. The strengthened anticorrelations were associated with improving clinical symptoms in the atomoxetine-treated adults. Our results support the idea that atypical default mode network task-positive network interaction plays an important role in the pathophysiology of adult attention-deficit hyperactivity disorder. Strengthening this atypical relationship following atomoxetine treatment suggests an important pathway to treat attention-deficit hyperactivity disorder. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Mental disorders are not brain disorders.

PubMed

Banner, Natalie F

2013-06-01

As advances in neuroscience and genetics reveal complex associations between brain structures, functions and symptoms of mental disorders, there have been calls for psychiatric classifications to be reconfigured, to conceptualize mental disorders as disorders of the brain. In this paper, I argue that this view is mistaken, and that the level at which we identify mental disorders is, and should be, the person, not the brain. This is not to deny physicalism or argue that the mental realm is somehow distinct from the physical, but rather to suggest the things that are going 'wrong' in mental disorder are picked out at the person-level: they are characterized by breaches in epistemic, rational, evaluative, emotional, social and moral norms. However, as our scientific understanding of the brain becomes advanced, what makes an identified neurobiological difference in brain structure or functioning indicative of pathology is its association with these behaviours at the person-level. Instead of collapsing psychiatry into biomedicine, biomedicine may benefit from drawing closer to the expertise of psychiatry, as it is able to accommodate social, psychological and biological explanations while focusing on the person, within their environment. © 2013 John Wiley & Sons Ltd.

Optimizing real time fMRI neurofeedback for therapeutic discovery and development

PubMed Central

Stoeckel, L.E.; Garrison, K.A.; Ghosh, S.; Wighton, P.; Hanlon, C.A.; Gilman, J.M.; Greer, S.; Turk-Browne, N.B.; deBettencourt, M.T.; Scheinost, D.; Craddock, C.; Thompson, T.; Calderon, V.; Bauer, C.C.; George, M.; Breiter, H.C.; Whitfield-Gabrieli, S.; Gabrieli, J.D.; LaConte, S.M.; Hirshberg, L.; Brewer, J.A.; Hampson, M.; Van Der Kouwe, A.; Mackey, S.; Evins, A.E.

2014-01-01

While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health, the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain–behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders. PMID:25161891

Sleep and Psychiatric Disorders in Persons With Mild Traumatic Brain Injury.

PubMed

Mollayeva, Tatyana; D'Souza, Andrea; Mollayeva, Shirin

2017-08-01

Mild traumatic brain injury (mTBI) frequently challenges the integrity of sleep function by affecting multiple brain areas implicated in controlling the switch between wakefulness and sleep and those involved in circadian and homeostatic processes; the malfunction of each causes a variety of disorders. In this review, we discuss recent data on the dynamics between disorders of sleep and mental/psychiatric disorders in persons with mTBI. This analysis sets the stage for understanding how a variety of physiological, emotional and environmental influences affect sleep and mental activities after injury to the brain. Consideration of the intricate links between sleep and mental functions in future research can increase understanding on the underlying mechanisms of sleep-related and psychiatric comorbidity in mTBI.

Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

PubMed

Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E

2015-07-01

Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family members. Additionally, while age had a relatively strong impact on all neurocognitive traits, the effects of age on cognition did not differ between diagnostic groups. Most brain-behaviour associations were also similar across the age range, with the exception of cortical and ventricular volume and lingual gyrus thickness, which showed weak correlations with verbal fluency and inhibitory control at younger ages that increased in magnitude in older subjects, regardless of diagnosis. Findings indicate that neuroanatomical traits potentially impacted by bipolar disorder are significantly associated with multiple neurobehavioural domains. Structure-function relationships are generally preserved across diagnostic groups, with the notable exception of ventrolateral prefrontal and parietal association cortex, volumetric increases in which may be associated with cognitive resilience specifically in individuals with bipolar disorder. Although age impacted all neurobehavioural traits, we did not find any evidence of accelerated cognitive decline specific to bipolar disorder subjects. Regardless of diagnosis, greater global brain volume may represent a protective factor for the effects of ageing on executive functioning. © 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.

Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior.

PubMed

Patrick, Rhonda P; Ames, Bruce N

2015-06-01

Serotonin regulates a wide variety of brain functions and behaviors. Here, we synthesize previous findings that serotonin regulates executive function, sensory gating, and social behavior and that attention deficit hyperactivity disorder, bipolar disorder, schizophrenia, and impulsive behavior all share in common defects in these functions. It has remained unclear why supplementation with omega-3 fatty acids and vitamin D improve cognitive function and behavior in these brain disorders. Here, we propose mechanisms by which serotonin synthesis, release, and function in the brain are modulated by vitamin D and the 2 marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Brain serotonin is synthesized from tryptophan by tryptophan hydroxylase 2, which is transcriptionally activated by vitamin D hormone. Inadequate levels of vitamin D (∼70% of the population) and omega-3 fatty acids are common, suggesting that brain serotonin synthesis is not optimal. We propose mechanisms by which EPA increases serotonin release from presynaptic neurons by reducing E2 series prostaglandins and DHA influences serotonin receptor action by increasing cell membrane fluidity in postsynaptic neurons. We propose a model whereby insufficient levels of vitamin D, EPA, or DHA, in combination with genetic factors and at key periods during development, would lead to dysfunctional serotonin activation and function and may be one underlying mechanism that contributes to neuropsychiatric disorders and depression. This model suggests that optimizing vitamin D and marine omega-3 fatty acid intake may help prevent and modulate the severity of brain dysfunction. © FASEB.

Pathophysiological implications of neurovascular P450 in brain disorders

PubMed Central

Ghosh, Chaitali; Hossain, Mohammed; Solanki, Jesal; Dadas, Aaron; Marchi, Nicola; Janigro, Damir

2016-01-01

Over the past decades, the significance of cytochrome P450 (CYP) enzymes has expanded beyond their role as peripheral drug metabolizers in the liver and gut. CYP enzymes are also functionally active at the neurovascular interface. CYP expression is modulated by disease states, impacting cellular functions, detoxification, and reactivity to toxic stimuli and brain drug biotransformation. Unveiling the physiological and molecular complexity of brain P450 enzymes will improve our understanding of the mechanisms underlying brain drug availability, pharmacological efficacy, and neurotoxic adverse effects from pharmacotherapy targeting brain disorders. PMID:27312874

Brain Activation during Semantic Processing in Autism Spectrum Disorders via Functional Magnetic Resonance Imaging

ERIC Educational Resources Information Center

Harris, Gordon J.; Chabris, Christopher F.; Clark, Jill; Urban, Trinity; Aharon, Itzhak; Steele, Shelley; McGrath, Lauren; Condouris, Karen; Tager-Flusberg, Helen

2006-01-01

Language and communication deficits are core features of autism spectrum disorders (ASD), even in high-functioning adults with ASD. This study investigated brain activation patterns using functional magnetic resonance imaging in right-handed adult males with ASD and a control group, matched on age, handedness, and verbal IQ. Semantic processing in…

Altered brain functional networks in people with Internet gaming disorder: Evidence from resting-state fMRI.

PubMed

Wang, Lingxiao; Wu, Lingdan; Lin, Xiao; Zhang, Yifen; Zhou, Hongli; Du, Xiaoxia; Dong, Guangheng

2016-08-30

Although numerous neuroimaging studies have detected structural and functional abnormality in specific brain regions and connections in subjects with Internet gaming disorder (IGD), the topological organization of the whole-brain network in IGD remain unclear. In this study, we applied graph theoretical analysis to explore the intrinsic topological properties of brain networks in Internet gaming disorder (IGD). 37 IGD subjects and 35 matched healthy control (HC) subjects underwent a resting-state functional magnetic resonance imaging scan. The functional networks were constructed by thresholding partial correlation matrices of 90 brain regions. Then we applied graph-based approaches to analysis their topological attributes, including small-worldness, nodal metrics, and efficiency. Both IGD and HC subjects show efficient and economic brain network, and small-world topology. Although there was no significant group difference in global topology metrics, the IGD subjects showed reduced regional centralities in the prefrontal cortex, left posterior cingulate cortex, right amygdala, and bilateral lingual gyrus, and increased functional connectivity in sensory-motor-related brain networks compared to the HC subjects. These results imply that people with IGD may be associated with functional network dysfunction, including impaired executive control and emotional management, but enhanced coordination among visual, sensorimotor, auditory and visuospatial systems. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Abnormal activation of the occipital lobes during emotion picture processing in major depressive disorder patients

PubMed Central

Li, Jianying; Xu, Cheng; Cao, Xiaohua; Gao, Qiang; Wang, Yan; Wang, Yanfang; Peng, Juyi; Zhang, Kerang

2013-01-01

A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe, temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for cognitive disorder in depressed patients. PMID:25206466

Identification of autism spectrum disorder using deep learning and the ABIDE dataset.

PubMed

Heinsfeld, Anibal Sólon; Franco, Alexandre Rosa; Craddock, R Cameron; Buchweitz, Augusto; Meneguzzi, Felipe

2018-01-01

The goal of the present study was to apply deep learning algorithms to identify autism spectrum disorder (ASD) patients from large brain imaging dataset, based solely on the patients brain activation patterns. We investigated ASD patients brain imaging data from a world-wide multi-site database known as ABIDE (Autism Brain Imaging Data Exchange). ASD is a brain-based disorder characterized by social deficits and repetitive behaviors. According to recent Centers for Disease Control data, ASD affects one in 68 children in the United States. We investigated patterns of functional connectivity that objectively identify ASD participants from functional brain imaging data, and attempted to unveil the neural patterns that emerged from the classification. The results improved the state-of-the-art by achieving 70% accuracy in identification of ASD versus control patients in the dataset. The patterns that emerged from the classification show an anticorrelation of brain function between anterior and posterior areas of the brain; the anticorrelation corroborates current empirical evidence of anterior-posterior disruption in brain connectivity in ASD. We present the results and identify the areas of the brain that contributed most to differentiating ASD from typically developing controls as per our deep learning model.

Neural Signatures of Autism Spectrum Disorders: Insights into Brain Network Dynamics

PubMed Central

Hernandez, Leanna M; Rudie, Jeffrey D; Green, Shulamite A; Bookheimer, Susan; Dapretto, Mirella

2015-01-01

Neuroimaging investigations of autism spectrum disorders (ASDs) have advanced our understanding of atypical brain function and structure, and have recently converged on a model of altered network-level connectivity. Traditional task-based functional magnetic resonance imaging (MRI) and volume-based structural MRI studies have identified widespread atypicalities in brain regions involved in social behavior and other core ASD-related behavioral deficits. More recent advances in MR-neuroimaging methods allow for quantification of brain connectivity using diffusion tensor imaging, functional connectivity, and graph theoretic methods. These newer techniques have moved the field toward a systems-level understanding of ASD etiology, integrating functional and structural measures across distal brain regions. Neuroimaging findings in ASD as a whole have been mixed and at times contradictory, likely due to the vast genetic and phenotypic heterogeneity characteristic of the disorder. Future longitudinal studies of brain development will be crucial to yield insights into mechanisms of disease etiology in ASD sub-populations. Advances in neuroimaging methods and large-scale collaborations will also allow for an integrated approach linking neuroimaging, genetics, and phenotypic data. PMID:25011468

EEG mapping and low-resolution brain electromagnetic tomography (LORETA) in diagnosis and therapy of psychiatric disorders: evidence for a key-lock principle.

PubMed

Saletu, Bernd; Anderer, Peter; Saletu-Zyhlarz, Gerda M; Pascual-Marqui, Roberto D

2005-04-01

Different psychiatric disorders, such as schizophrenia with predominantly positive and negative symptomatology, major depression, generalized anxiety disorder, agoraphobia, obsessive-compulsive disorder, multi-infarct dementia, senile dementia of the Alzheimer type and alcohol dependence, show EEG maps that differ statistically both from each other and from normal controls. Representative drugs of the main psychopharmacological classes, such as sedative and non-sedative neuroleptics and antidepressants, tranquilizers, hypnotics, psychostimulants and cognition-enhancing drugs, induce significant and typical changes to normal human brain function, which in many variables are opposite to the above-mentioned differences between psychiatric patients and normal controls. Thus, by considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. This is supported by 3-dimensional low-resolution brain electromagnetic tomography (LORETA), which identifies regions within the brain that are affected by psychiatric disorders and psychopharmacological substances.

The hubs of the human connectome are generally implicated in the anatomy of brain disorders.

PubMed

Crossley, Nicolas A; Mechelli, Andrea; Scott, Jessica; Carletti, Francesco; Fox, Peter T; McGuire, Philip; Bullmore, Edward T

2014-08-01

Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports integrative processing and adaptive behaviours. Recent studies also suggest that hubs have higher metabolic demands and longer-distance connections than other brain regions, and therefore could be considered biologically costly. Assuming that hubs thus normally combine both high topological value and high biological cost, we predicted that pathological brain lesions would be concentrated in hub regions. To test this general hypothesis, we first identified the hubs of brain anatomical networks estimated from diffusion tensor imaging data on healthy volunteers (n = 56), and showed that computational attacks targeted on hubs disproportionally degraded the efficiency of brain networks compared to random attacks. We then prepared grey matter lesion maps, based on meta-analyses of published magnetic resonance imaging data on more than 20 000 subjects and 26 different brain disorders. Magnetic resonance imaging lesions that were common across all brain disorders were more likely to be located in hubs of the normal brain connectome (P < 10(-4), permutation test). Specifically, nine brain disorders had lesions that were significantly more likely to be located in hubs (P < 0.05, permutation test), including schizophrenia and Alzheimer's disease. Both these disorders had significantly hub-concentrated lesion distributions, although (almost completely) distinct subsets of cortical hubs were lesioned in each disorder: temporal lobe hubs specifically were associated with higher lesion probability in Alzheimer's disease, whereas in schizophrenia lesions were concentrated in both frontal and temporal cortical hubs. These results linking pathological lesions to the topological centrality of nodes in the normal diffusion tensor imaging connectome were generally replicated when hubs were defined instead by the meta-analysis of more than 1500 task-related functional neuroimaging studies of healthy volunteers to create a normative functional co-activation network. We conclude that the high cost/high value hubs of human brain networks are more likely to be anatomically abnormal than non-hubs in many (if not all) brain disorders. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

Neuroimaging Insights into the Pathophysiology of Sleep Disorders

PubMed Central

Desseilles, Martin; Dang-Vu, Thanh; Schabus, Manuel; Sterpenich, Virginie; Maquet, Pierre; Schwartz, Sophie

2008-01-01

Neuroimaging methods can be used to investigate whether sleep disorders are associated with specific changes in brain structure or regional activity. However, it is still unclear how these new data might improve our understanding of the pathophysiology underlying adult sleep disorders. Here we review functional brain imaging findings in major intrinsic sleep disorders (i.e., idiopathic insomnia, narcolepsy, and obstructive sleep apnea) and in abnormal motor behavior during sleep (i.e., periodic limb movement disorder and REM sleep behavior disorder). The studies reviewed include neuroanatomical assessments (voxel-based morphometry, magnetic resonance spectroscopy), metabolic/functional investigations (positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging), and ligand marker measurements. Based on the current state of the research, we suggest that brain imaging is a useful approach to assess the structural and functional correlates of sleep impairments as well as better understand the cerebral consequences of various therapeutic approaches. Modern neuroimaging techniques therefore provide a valuable tool to gain insight into possible pathophysiological mechanisms of sleep disorders in adult humans. Citation: Desseilles M; Dang-Vu TD; Schabus M; Sterpenich V; Maquet P; Schwartz S. Neuroimaging insights into the pathophysiology of sleep disorders. SLEEP 2008;31(6):777–794. PMID:18548822

Effects of omega-3 polyunsaturated fatty acids on human brain morphology and function: What is the evidence?

PubMed

Bos, Dienke J; van Montfort, Simone J T; Oranje, Bob; Durston, Sarah; Smeets, Paul A M

2016-03-01

Public opinion and media coverage suggest that there are benefits of long-chain ω-3 polyunsaturated fatty acid (LC-PUFA) intake on brain functioning. However, it is an open question whether this is indeed the case. Therefore, we reviewed the evidence for effects of ω-3 LC-PUFA on human brain morphology and function. We included studies on (1) naturalistic long-term ω-3 LC-PUFA intake during life (2) the effects of short-term ω-3 LC-PUFA supplementation in healthy subjects and (3) the effects of ω-3 LC-PUFA supplementation as alternative or add-on treatment for psychiatric or neurological disorders. To date, 24 studies have been published on the effect of ω-3 LC-PUFA on brain function and structure. Findings from naturalistic studies and clinical trials in healthy individuals indicate that ω-3 LC-PUFA intake may be associated with increased functional activation of the prefrontal cortex in children, and greater gray matter volume and white matter integrity during aging. However, most naturalistic studies were cross-sectional or did not find any effect on cognition. As such, it is hard to estimate the magnitude of any beneficial effects. Furthermore, there is only limited evidence to support that ω-3 LC-PUFA supplementation is beneficial in brain disorders, such as Alzheimer's Disease, Attention Deficit/Hyperactivity Disorder, Major Depressive Disorder and schizophrenia. Overall, the literature suggests that sensitivity to supplementation may vary over development, and as a consequence of brain disorders. The biological mechanisms underlying any (beneficial) effects ω-3 LC-PUFAs on the brain are currently unknown and need to be investigated. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Alterations of Brain Functional Architecture Associated with Psychopathic Traits in Male Adolescents with Conduct Disorder.

PubMed

Pu, Weidan; Luo, Qiang; Jiang, Yali; Gao, Yidian; Ming, Qingsen; Yao, Shuqiao

2017-09-12

Psychopathic traits of conduct disorder (CD) have a core callous-unemotional (CU) component and an impulsive-antisocial component. Previous task-driven fMRI studies have suggested that psychopathic traits are associated with dysfunction of several brain areas involved in different cognitive functions (e.g., empathy, reward, and response inhibition etc.), but the relationship between psychopathic traits and intrinsic brain functional architecture has not yet been explored in CD. Using a holistic brain-wide functional connectivity analysis, this study delineated the alterations in brain functional networks in patients with conduct disorder. Compared with matched healthy controls, we found decreased anti-synchronization between the fronto-parietal network (FPN) and default mode network (DMN), and increased intra-network synchronization within the frontothalamic-basal ganglia, right frontoparietal, and temporal/limbic/visual networks in CD patients. Correlation analysis showed that the weakened FPN-DMN interaction was associated with CU traits, while the heightened intra-network functional connectivity was related to impulsivity traits in CD patients. Our findings suggest that decoupling of cognitive control (FPN) with social understanding of others (DMN) is associated with the CU traits, and hyper-functions of the reward and motor inhibition systems elevate impulsiveness in CD.

fMRI brain activation in patients with insomnia disorder during a working memory task.

PubMed

Son, Young-Don; Kang, Jae Myeong; Cho, Seong-Jin; Lee, Jung-Sun; Hwang, Hee Young; Kang, Seung-Gul

2018-05-01

This study used functional magnetic resonance imaging (fMRI) to investigate differences in the functional brain activation of patients with insomnia disorder (n = 21, mean age = 36.6) and of good sleepers (n = 26, mean age = 33.2) without other comorbidities or structural brain abnormalities during a working memory task. All participants completed a clinical questionnaire, were subjected to portable polysomnography (PSG), and performed the working memory task during an fMRI scan. The subjects who were suspected of major sleep disorder and comorbid psychiatric disorders except insomnia disorder were excluded. To compare the brain activation on working memory from the insomnia group with those from the good-sleeper group, a two-sample t test was performed. Statistical significance was determined using 3DClustSim with the updated algorithm to obtain a reasonable cluster size and p value for each analysis. We observed higher levels of brain activation in the right lateral inferior frontal cortex and the right superior temporal pole in the insomnia group compared to good sleepers (cluster-based multiple comparison correction, p < 0.001, k = 34 @ α = 0.01). Thus, patients with insomnia disorder showed increased brain activation during working memory relative to good sleepers, and this may be indicative of compensatory brain activation to maintain cognitive performance in patients with insomnia disorder without other comorbidities.

An Update Overview on Brain Imaging Studies of Internet Gaming Disorder

PubMed Central

Weinstein, Aviv M.

2017-01-01

There are a growing number of studies on structural and functional brain mechanisms underlying Internet gaming disorder (IGD). Recent functional magnetic resonance imaging studies showed that IGD adolescents and adults had reduced gray matter volume in regions associated with attention motor coordination executive function and perception. Adolescents with IGD showed lower white matter (WM) integrity measures in several brain regions that are involved in decision-making, behavioral inhibition, and emotional regulation. IGD adolescents had also disruption in the functional connectivity in areas responsible for learning memory and executive function, processing of auditory, visual, and somatosensory stimuli and relay of sensory and motor signals. IGD adolescents also had decreased functional connectivity of PFC-striatal circuits, increased risk-taking choices, and impaired ability to control their impulses similar to other impulse control disorders. Recent studies indicated that altered executive control mechanisms in attention deficit hyperactivity disorder (ADHD) would be a predisposition for developing IGD. Finally, patients with IGD have also shown an increased functional connectivity of several executive control brain regions that may related to comorbidity with ADHD and depression. The behavioral addiction model argues that IGD shows the features of excessive use despite adverse consequences, withdrawal phenomena, and tolerance that characterize substance use disorders. The evidence supports the behavioral addiction model of IGD by showing structural and functional changes in the mechanisms of reward and craving (but not withdrawal) in IGD. Future studies need to investigate WM density and functional connectivity in IGD in order to validate these findings. Furthermore, more research is required about the similarity in neurochemical and neurocognitive brain circuits in IGD and comorbid conditions such as ADHD and depression. PMID:29033857

[Fractal characteristics of the functional state of the brain in patients with anxious phobic disorders].

PubMed

Dik, O E; Sviatogor, I A; Ishinova, V A; Nozdrachev, A D

2012-01-01

The task of estimation of the functional state of the human brain during psychotherapeutic treatment of psychogenic pain in patients with anxious phobic disorders is examined. For solving the task the methods of spectral and multifractal analyses of EEG fragments are applied during the perception of psychogenic pain and its removal by the psychorelaxation technique. Contrary to power spectra singularity spectra allow to distinguish EEGs quanitatively in the examined functional states of the human brain. The pain suppression in patients with anxious phobic disorders during psychorelaxation is accompanied by changing the width of the singularity spectrum and approximation of this multifractal partameter to the value corresponding to a healthy subject.

Genetic control of postnatal human brain growth

PubMed Central

van Dyck, Laura I.; Morrow, Eric M.

2017-01-01

Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

Alpha oscillations and their impairment in affective and post-traumatic stress disorders.

PubMed

Eidelman-Rothman, Moranne; Levy, Jonathan; Feldman, Ruth

2016-09-01

Affective and anxiety disorders are debilitating conditions characterized by impairments in cognitive and social functioning. Elucidating their neural underpinnings may assist in improving diagnosis and developing targeted interventions. Neural oscillations are fundamental for brain functioning. Specifically, oscillations in the alpha frequency range (alpha rhythms) are prevalent in the awake, conscious brain and play an important role in supporting perceptual, cognitive, and social processes. We review studies utilizing various alpha power measurements to assess abnormalities in brain functioning in affective and anxiety disorders as well as obsessive compulsive and post-traumatic stress disorders. Despite some inconsistencies, studies demonstrate associations between aberrant alpha patterns and these disorders both in response to specific cognitive and emotional tasks and during a resting state. We conclude by discussing methodological considerations and future directions, and underscore the need for much further research on the role of alpha functionality in social contexts. As social dysfunction accompanies most psychiatric conditions, research on alpha's involvement in social processes may provide a unique window into the neural mechanisms underlying these disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Leptin and the brain: influences on brain development, cognitive functioning and psychiatric disorders.

PubMed

Farr, Olivia M; Tsoukas, Michael A; Mantzoros, Christos S

2015-01-01

Receptors of leptin, the prototypical adipokine, are expressed throughout the cortex and several other areas of the brain. Although typically studied for its role in energy intake and expenditure, leptin plays a critical role in many other neurocognitive processes and interacts with various other hormones and neurotransmitters to perform these functions. Here, we review the literature on how leptin influences brain development, neural degradation, Alzheimer's disease, psychiatric disorders, and more complicated cognitive functioning and feeding behaviors. We also discuss modulators of leptin and the leptin receptor as they relate to normal cognitive functioning and may mediate some of the actions of leptin in the brain. Although we are beginning to better understand the critical role leptin plays in normal cognitive functioning, there is much to be discovered. Copyright © 2015 Elsevier Inc. All rights reserved.

Evolving knowledge of sex differences in brain structure, function, and chemistry.

PubMed

Cosgrove, Kelly P; Mazure, Carolyn M; Staley, Julie K

2007-10-15

Clinical and epidemiologic evidence demonstrates sex differences in the prevalence and course of various psychiatric disorders. Understanding sex-specific brain differences in healthy individuals is a critical first step toward understanding sex-specific expression of psychiatric disorders. Here, we evaluate evidence on sex differences in brain structure, chemistry, and function using imaging methodologies, including functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and structural magnetic resonance imaging (MRI) in mentally healthy individuals. MEDLINE searches of English-language literature (1980-November 2006) using the terms sex, gender, PET, SPECT, MRI, fMRI, morphometry, neurochemistry, and neurotransmission were performed to extract relevant sources. The literature suggests that while there are many similarities in brain structure, function, and neurotransmission in healthy men and women, there are important differences that distinguish the male from the female brain. Overall, brain volume is greater in men than women; yet, when controlling for total volume, women have a higher percentage of gray matter and men a higher percentage of white matter. Regional volume differences are less consistent. Global cerebral blood flow is higher in women than in men. Sex-specific differences in dopaminergic, serotonergic, and gamma-aminobutyric acid (GABA)ergic markers indicate that male and female brains are neurochemically distinct. Insight into the etiology of sex differences in the normal living human brain provides an important foundation to delineate the pathophysiological mechanisms underlying sex differences in neuropsychiatric disorders and to guide the development of sex-specific treatments for these devastating brain disorders.

CEREBRAL BLOOD FLOW AND METABOLISM IN ANXIETY AND ANXIETY DISORDERS

PubMed Central

Mathew, Roy J.

1994-01-01

Anxiety disorders are some of the commonest psychiatric disorders and anxiety commonly co-exists with other psychiatric conditions. Anxiety can also be a normal emotion. Thus, study of the neurobiological effects of anxiety is of considerable significance. In the normal brain, cerebral blood flow (CBF) and metabolism (CMR) serve as indices of brain function. CBF/CMR research is expected to provide new insight into alterations in brain function in anxiety disorders and other psychiatric disorders. Possible associations between stress I anxiety I panic and cerebral ischemia I stroke give additional significance to the effects of anxiety on CBF. With the advent of non-invasive techniques, study of CBF/CMR in anxiety disorders became easier. A large numbers of research reports are available on the effects of stress, anxiety and panic on CBF/CMR in normals and anxiety disorder patients. This article reviews the available human research on this topic. PMID:21743685

The Role of Sleep in Emotional Brain Function

PubMed Central

Goldstein, Andrea N.; Walker, Matthew P.

2014-01-01

Rapidly emerging evidence continues to describe an intimate and causal relationship between sleep and emotional brain function. These findings are mirrored by longstanding clinical observations demonstrating that nearly all mood and anxiety disorders co-occur with one or more sleep abnormalities. This review aims to (1) provide a synthesis of recent findings describing the emotional brain and behavioral benefits triggered by sleep, and conversely, the detrimental impairments following a lack of sleep, (2) outline a proposed framework in which sleep, and specifically rapid-eye movement (REM) sleep, supports a process of affective brain homeostasis, optimally preparing the organism for next-day social and emotional functioning, and (3) describe how this hypothesized framework can explain the prevalent relationships between sleep and psychiatric disorders, with a particular focus on post-traumatic stress disorder and major depression. PMID:24499013

The epigenetic switches for neural development and psychiatric disorders.

PubMed

Lv, Jingwen; Xin, Yongjuan; Zhou, Wenhao; Qiu, Zilong

2013-07-20

The most remarkable feature of the nervous system is that the development and functions of the brain are largely reshaped by postnatal experiences, in joint with genetic landscapes. The nature vs. nurture argument reminds us that both genetic and epigenetic information is indispensable for the normal function of the brain. The epigenetic regulatory mechanisms in the central nervous system have been revealed over last a decade. Moreover, the mutations of epigenetic modulator genes have been shown to be implicated in neuropsychiatric disorders, such as autism spectrum disorders. The epigenetic study has initiated in the neuroscience field for a relative short period of time. In this review, we will summarize recent discoveries about epigenetic regulation on neural development, synaptic plasticity, learning and memory, as well as neuropsychiatric disorders. Although the comprehensive view of how epigenetic regulation contributes to the function of the brain is still not completed, the notion that brain, the most complicated organ of organisms, is profoundly shaped by epigenetic switches is widely accepted. Copyright © 2013. Published by Elsevier Ltd.

Genetic and Diagnostic Biomarker Development in ASD Toddlers Using Resting State Functional MRI

DTIC Science & Technology

2016-09-01

networks during resting states. Autism spectrum disorder (ASD) begins prenatal, and early maldevelopment is present in many sites and systems that mediate...molecular and genomic evidence indicates autism spectrum disorder (ASD) begins prenatally, most likely by or before the late second trimester 10-15 as...ages 3 to 4 years. 2. KEYWORDS Autism spectrum disorder, ASD, early brain development, intrinsic functional brain networks, fMRI, infants, toddlers

The Neuroanatomy of Autism Spectrum Disorder: An Overview of Structural Neuroimaging Findings and Their Translatability to the Clinical Setting

ERIC Educational Resources Information Center

Ecker, Christine

2017-01-01

Autism spectrum disorder is a complex neurodevelopmental disorder, which is accompanied by differences in brain anatomy, functioning and brain connectivity. Due to its neurodevelopmental character, and the large phenotypic heterogeneity among individuals on the autism spectrum, the neurobiology of autism spectrum disorder is inherently difficult…

Neural, electrophysiological and anatomical basis of brain-network variability and its characteristic changes in mental disorders.

PubMed

Zhang, Jie; Cheng, Wei; Liu, Zhaowen; Zhang, Kai; Lei, Xu; Yao, Ye; Becker, Benjamin; Liu, Yicen; Kendrick, Keith M; Lu, Guangming; Feng, Jianfeng

2016-08-01

SEE MATTAR ET AL DOI101093/AWW151 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Functional brain networks demonstrate significant temporal variability and dynamic reconfiguration even in the resting state. Currently, most studies investigate temporal variability of brain networks at the scale of single (micro) or whole-brain (macro) connectivity. However, the mechanism underlying time-varying properties remains unclear, as the coupling between brain network variability and neural activity is not readily apparent when analysed at either micro or macroscales. We propose an intermediate (meso) scale analysis and characterize temporal variability of the functional architecture associated with a particular region. This yields a topography of variability that reflects the whole-brain and, most importantly, creates an analytical framework to establish the fundamental relationship between variability of regional functional architecture and its neural activity or structural connectivity. We find that temporal variability reflects the dynamical reconfiguration of a brain region into distinct functional modules at different times and may be indicative of brain flexibility and adaptability. Primary and unimodal sensory-motor cortices demonstrate low temporal variability, while transmodal areas, including heteromodal association areas and limbic system, demonstrate the high variability. In particular, regions with highest variability such as hippocampus/parahippocampus, inferior and middle temporal gyrus, olfactory gyrus and caudate are all related to learning, suggesting that the temporal variability may indicate the level of brain adaptability. With simultaneously recorded electroencephalography/functional magnetic resonance imaging and functional magnetic resonance imaging/diffusion tensor imaging data, we also find that variability of regional functional architecture is modulated by local blood oxygen level-dependent activity and α-band oscillation, and is governed by the ratio of intra- to inter-community structural connectivity. Application of the mesoscale variability measure to multicentre datasets of three mental disorders and matched controls involving 1180 subjects reveals that those regions demonstrating extreme, i.e. highest/lowest variability in controls are most liable to change in mental disorders. Specifically, we draw attention to the identification of diametrically opposing patterns of variability changes between schizophrenia and attention deficit hyperactivity disorder/autism. Regions of the default-mode network demonstrate lower variability in patients with schizophrenia, but high variability in patients with autism/attention deficit hyperactivity disorder, compared with respective controls. In contrast, subcortical regions, especially the thalamus, show higher variability in schizophrenia patients, but lower variability in patients with attention deficit hyperactivity disorder. The changes in variability of these regions are also closely related to symptom scores. Our work provides insights into the dynamic organization of the resting brain and how it changes in brain disorders. The nodal variability measure may also be potentially useful as a predictor for learning and neural rehabilitation. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: A review of human brain oscillations as effective endophenotypes

PubMed Central

Rangaswamy, Madhavi; Porjesz, Bernice

2010-01-01

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders. PMID:18634760

Uncovering genes for cognitive (dys)function and predisposition for alcoholism spectrum disorders: a review of human brain oscillations as effective endophenotypes.

PubMed

Rangaswamy, Madhavi; Porjesz, Bernice

2008-10-15

Brain oscillations provide a rich source of potentially useful endophenotypes (intermediate phenotypes) for psychiatric genetics, as they represent important correlates of human information processing and are associated with fundamental processes from perception to cognition. These oscillations are highly heritable, are modulated by genes controlling neurotransmitters in the brain, and provide links to associative and integrative brain functions. These endophenotypes represent traits that are less complex and more proximal to gene function than either diagnostic labels or traditional cognitive measures, providing a powerful strategy in searching for genes in psychiatric disorders. These intermediate phenotypes identify both affected and unaffected members of an affected family, including offspring at risk, providing a more direct connection with underlying biological vulnerability. Our group has utilized heritable neurophysiological features (i.e., brain oscillations) as endophenotypes, making it possible to identify susceptibility genes that may be difficult to detect with diagnosis alone. We have discussed our findings of significant linkage and association between brain oscillations and genes in GABAergic, cholinergic and glutamatergic systems (GABRA2, CHRM2, and GRM8). We have also shown that some oscillatory indices from both resting and active cognitive states have revealed a common subset of genetic foci that are shared with the diagnosis of alcoholism and related disorders. Implications of our findings have been discussed in the context of physiological and pharmacological studies on receptor function. These findings underscore the utility of quantitative neurophysiological endophenotypes in the study of the genetics of brain function and the genetic diathesis underlying complex psychiatric disorders.

Larger Brains in Medication Naive High-Functioning Subjects with Pervasive Developmental Disorder

ERIC Educational Resources Information Center

Palmen, Saskia J. M. C.; Pol, Hilleke E. Hulshoff; Kemner, Chantal; Schnack, Hugo G.; Janssen, Joost; Kahn, Rene S.; van Engeland, Herman

2004-01-01

Background: Are brain volumes of individuals with Pervasive Developmental Disorder (PDD) still enlarged in adolescence and adulthood, and if so, is this enlargement confined to the gray and/or the white matter and is it global or more prominent in specific brain regions. Methods: Brain MRI scans were made of 21 adolescents with PDD and 21 closely…

Korean Brain Rehabilitation Registry for Rehabilitation of Persons with Brain Disorders: Annual Report in 2009

PubMed Central

Yang, Seung Nam; Park, Si-Woon; Jung, Han Young; Rah, Ueon Woo; Kim, Yun-Hee; Chun, Min Ho; Paik, Nam-Jong; Yoo, Seung Don; Pyun, Sung-Bom; Kim, Min Wook; Lee, Sam-Gyu; Park, Byung Kyu; Shin, Heesuk; Shin, Yong Il; Lee, Heeyeon

2012-01-01

This first annual report provides a description of patients discharged from rehabilitation facilities in Korea based on secondary data analysis of Korean Brain Rehabilitation Registry V1.0 subscribed in 2009. The analysis included 1,697 records of patients with brain disorders including stroke, traumatic brain injury, brain tumor and other disorders from 24 rehabilitation facilities across Korea. The data comprised 1,380 cases of stroke, 104 cases of brain injury, 55 cases of brain tumor, and 58 cases of other brain diseases. The functional status of each patient was measured using the Korean version of the Modified Barthel Index (KMBI). The average change in the KMBI score was 15.9 for all patients in the inpatient rehabilitation facility. The average length of stay for inpatient rehabilitation was 36.9 days. The transfer rates to other hospitals were high, being 62.4% when all patients were considered. Patients with brain disorders of Korea in 2009 and measurable functional improvement was observed in patients. However, relatively high percentages of patients were not discharged to the community after inpatient rehabilitation. Based on the results of this study, consecutive reports of the status of rehabilitation need to be conducted in order to provide useful information to many practitioners. PMID:22690103

Multimodal Brain Imaging in Autism Spectrum Disorder and the Promise of Twin Research

ERIC Educational Resources Information Center

Mevel, Katell; Fransson, Peter; Bölte, Sven

2015-01-01

Current evidence suggests the phenotype of autism spectrum disorder to be driven by a complex interaction of genetic and environmental factors impacting onto brain maturation, synaptic function, and cortical networks. However, findings are heterogeneous, and the exact neurobiological pathways of autism spectrum disorder still remain poorly…

Brain Structure Abnormalities in Adolescent Girls with Conduct Disorder

ERIC Educational Resources Information Center

Fairchild, Graeme; Hagan, Cindy C.; Walsh, Nicholas D.; Passamonti, Luca; Calder, Andrew J.; Goodyer, Ian M.

2013-01-01

Background: Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD.…

Somatic influences on subjective well-being and affective disorders: the convergence of thermosensory and central serotonergic systems

PubMed Central

Raison, Charles L.; Hale, Matthew W.; Williams, Lawrence E.; Wager, Tor D.; Lowry, Christopher A.

2015-01-01

Current theories suggest that the brain is the sole source of mental illness. However, affective disorders, and major depressive disorder (MDD) in particular, may be better conceptualized as brain-body disorders that involve peripheral systems as well. This perspective emphasizes the embodied, multifaceted physiology of well-being, and suggests that afferent signals from the body may contribute to cognitive and emotional states. In this review, we focus on evidence from preclinical and clinical studies suggesting that afferent thermosensory signals contribute to well-being and depression. Although thermoregulatory systems have traditionally been conceptualized as serving primarily homeostatic functions, increasing evidence suggests neural pathways responsible for regulating body temperature may be linked more closely with emotional states than previously recognized, an affective warmth hypothesis. Human studies indicate that increasing physical warmth activates brain circuits associated with cognitive and affective functions, promotes interpersonal warmth and prosocial behavior, and has antidepressant effects. Consistent with these effects, preclinical studies in rodents demonstrate that physical warmth activates brain serotonergic neurons implicated in antidepressant-like effects. Together, these studies suggest that (1) thermosensory pathways interact with brain systems that control affective function, (2) these pathways are dysregulated in affective disorders, and (3) activating warm thermosensory pathways promotes a sense of well-being and has therapeutic potential in the treatment of affective disorders. PMID:25628593

A systematic review of associations between functional MRI activity and polygenic risk for schizophrenia and bipolar disorder.

PubMed

Dezhina, Zalina; Ranlund, Siri; Kyriakopoulos, Marinos; Williams, Steve C R; Dima, Danai

2018-05-10

Genetic factors account for up to 80% of the liability for schizophrenia (SCZ) and bipolar disorder (BD). Genome-wide association studies have successfully identified several genes associated with increased risk for both disorders. This has allowed researchers to model the aggregate effect of genes associated with disease status and create a polygenic risk score (PGRS) for each individual. The interest in imaging genetics using PGRS has grown in recent years, with several studies now published. We have conducted a systematic review to examine the effects of PGRS of SCZ, BD and cross psychiatric disorders on brain function and connectivity using fMRI data. Results indicate that the effect of genetic load for SCZ and BD on brain function affects task-related recruitment, with frontal areas having a more prominent role, independent of task. Additionally, the results suggest that the polygenic architecture of psychotic disorders is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions. Future imaging genetics studies with large samples, especially population studies, would be uniquely informative in mapping the spatial distribution of the genetic risk to psychiatric disorders on brain processes during various cognitive tasks and may lead to the discovery of biological pathways that could be crucial in mediating the link between genetic factors and alterations in brain networks.

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder

PubMed Central

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-01-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC–vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder. PMID:28944772

Multimodal Investigation of Network Level Effects Using Intrinsic Functional Connectivity, Anatomical Covariance, and Structure-to-Function Correlations in Unmedicated Major Depressive Disorder.

PubMed

Scheinost, Dustin; Holmes, Sophie E; DellaGioia, Nicole; Schleifer, Charlie; Matuskey, David; Abdallah, Chadi G; Hampson, Michelle; Krystal, John H; Anticevic, Alan; Esterlis, Irina

2018-04-01

Converging evidence suggests that major depressive disorder (MDD) affects multiple large-scale brain networks. Analyses of the correlation or covariance of regional brain structure and function applied to structural and functional MRI data may provide insights into systems-level organization and structure-to-function correlations in the brain in MDD. This study applied tensor-based morphometry and intrinsic connectivity distribution to identify regions of altered volume and intrinsic functional connectivity in data from unmedicated individuals with MDD (n=17) and healthy comparison participants (HC, n=20). These regions were then used as seeds for exploratory anatomical covariance and connectivity analyses. Reduction in volume in the anterior cingulate cortex (ACC) and lower structural covariance between the ACC and the cerebellum were observed in the MDD group. Additionally, individuals with MDD had significantly lower whole-brain intrinsic functional connectivity in the medial prefrontal cortex (mPFC). This mPFC region showed altered connectivity to the ventral lateral PFC (vlPFC) and local circuitry in MDD. Global connectivity in the ACC was negatively correlated with reported depressive symptomatology. The mPFC-vlPFC connectivity was positively correlated with depressive symptoms. Finally, we observed increased structure-to-function correlation in the PFC/ACC in the MDD group. Although across all analysis methods and modalities alterations in the PFC/ACC were a common finding, each modality and method detected alterations in subregions belonging to distinct large-scale brain networks. These exploratory results support the hypothesis that MDD is a systems level disorder affecting multiple brain networks located in the PFC and provide new insights into the pathophysiology of this disorder.

Abnormal functional brain connectivity and personality traits in myotonic dystrophy type 1.

PubMed

Serra, Laura; Silvestri, Gabriella; Petrucci, Antonio; Basile, Barbara; Masciullo, Marcella; Makovac, Elena; Torso, Mario; Spanò, Barbara; Mastropasqua, Chiara; Harrison, Neil A; Bianchi, Maria L E; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

2014-05-01

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy observed in adults, is a genetic multisystem disorder affecting several other organs besides skeletal muscle, including the brain. Cognitive and personality abnormalities have been reported; however, no studies have investigated brain functional networks and their relationship with personality traits/disorders in patients with DM1. To use resting-state functional magnetic resonance imaging to assess the potential relationship between personality traits/disorders and changes to functional connectivity within the default mode network (DMN) in patients with DM1. We enrolled 27 patients with genetically confirmed DM1 and 16 matched healthy control individuals. Patients underwent personality assessment using clinical interview and Minnesota Multiphasic Personality Inventory-2 administration; all participants underwent resting-state functional magnetic resonance imaging. Investigations were conducted at the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Catholic University of Sacred Heart, and Azienda Ospedaliera San Camillo Forlanini. Resting-state functional magnetic resonance imaging. Measures of personality traits in patients and changes in functional connectivity within the DMN in patients and controls. Changes in functional connectivity and atypical personality traits in patients were correlated. We combined results obtained from the Minnesota Multiphasic Personality Inventory-2 and clinical interview to identify a continuum of atypical personality profiles ranging from schizotypal personality traits to paranoid personality disorder within our DM1 patients. We also demonstrated an increase in functional connectivity in the bilateral posterior cingulate and left parietal DMN nodes in DM1 patients compared with controls. Moreover, patients with DM1 showed strong associations between DMN functional connectivity and schizotypal-paranoid traits. Our findings provide novel biological evidence that DM1 is a clinical condition that also involves an alteration of functional connectivity of the brain. We speculate that these functional brain abnormalities, similarly to frank psychiatric disorders, may account for the atypical personality traits observed in patients with DM1.

Relationship between diet, the gut microbiota, and brain function.

PubMed

Tengeler, Anouk C; Kozicz, Tamas; Kiliaan, Amanda J

2018-04-28

The human intestinal microbiota, comprising trillions of microorganisms, exerts a substantial effect on the host. The microbiota plays essential roles in the function and development of several physiological processes, including those in the brain. A disruption in the microbial composition of the gut has been associated with many metabolic, inflammatory, neurodevelopmental, and neurodegenerative disorders. Nutrition is one of several key factors that shape the microbial composition during infancy and throughout life, thereby affecting brain structure and function. This review examines the effect of the gut microbiota on brain function. The ability of external factors, such as diet, to influence the microbial composition implies a certain vulnerability of the gut microbiota. However, it also offers a potential therapeutic strategy for ameliorating symptoms of mental and physical disorders. Therefore, this review examines the potential effect of nutritional components on gut microbial composition and brain function.

Thermodynamic laws apply to brain function.

PubMed

Salerian, Alen J

2010-02-01

Thermodynamic laws and complex system dynamics govern brain function. Thus, any change in brain homeostasis by an alteration in brain temperature, neurotransmission or content may cause region-specific brain dysfunction. This is the premise for the Salerian Theory of Brain built upon a new paradigm for neuropsychiatric disorders: the governing influence of neuroanatomy, neurophysiology, thermodynamic laws. The principles of region-specific brain function thermodynamics are reviewed. The clinical and supporting evidence including the paradoxical effects of various agents that alter brain homeostasis is demonstrated.

Cross-hemispheric functional connectivity in the human fetal brain.

PubMed

Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

2013-02-20

Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

The Major Histocompatibility Complex and Autism Spectrum Disorder

PubMed Central

Needleman, Leigh A.; McAllister, A. Kimberley

2015-01-01

Autism spectrum disorder (ASD) is a complex disorder that appears to be caused by interactions between genetic changes and environmental insults during early development. A wide range of factors have been linked to the onset of ASD, but recently both genetic associations and environmental factors point to a central role for immune- related genes and immune responses to environmental stimuli. Specifically, many of the proteins encoded by the major histocompatibility complex (MHC) play a vital role in the formation, refinement, maintenance, and plasticity of the brain. Manipulations of levels of MHC molecules have illustrated how disrupted MHC signaling can significantly alter brain connectivity and function. Thus, an emerging hypothesis in our field is that disruptions in MHC expression in the developing brain caused by mutations and/or immune dysregulation may contribute to the altered brain connectivity and function characteristic of ASD. This review provides an overview of the structure and function of the three classes of MHC molecules in the immune system, healthy brain, and their possible involvement in ASD. PMID:22760919

Are Mental Disorders Brain Diseases, and What Does This Mean? A Clinical-Neuropsychological Perspective.

PubMed

Frisch, Stefan

Neuroscientific research has substantially increased our knowledge about mental disorders in recent years. Along with these benefits, radical postulates have been articulated according to which understanding and treatment of mental disorders should generally be based on biological terms, such as neurons/brain areas, transmitters, genes etc. Proponents of such a 'biological psychiatry' claim that mental disorders are analogous to neurological disorders and refer to neurology and neuropsychology to corroborate their claims. The present article argues that, from a clinical-neuropsychological perspective, 'biological psychiatry' is based on a mechanistic, 'cerebrocentric' framework of brain (dys-)function which has its roots in experimental neuroscience but runs up against narrow limits in clinical neurology and neuropsychology. In fact, understanding and treating neurological disorders generally demands a systems perspective including brain, organism and environment as intrinsically entangled. In this way, 'biological' characterizes a 'holistic', nonreductionist level of explanation, according to which the significance of particular mechanisms can only be estimated in the context of the organism (or person). This is evident in the common observation that local brain damage does not just lead to an isolated loss of function, but to multiple attempts of reorganization and readaptation; it initiates new developments. Furthermore, treating brain disorders necessarily includes aspects of individuality and subjectivity, a conclusion that contradicts the purely 'objectivist', third-person stance put forward by some proponents of biological psychiatry. In sum, understanding and treating brain damage sequelae in the clinical neurosciences demands a biopsychosocial perspective, for both conceptual and historical reasons. The same may hold for psychiatry when adopting a brain-based view on mental disorders. In such a perspective, biological psychiatry seems an interesting project but falls short of its original claims. © 2016 S. Karger AG, Basel.

Long-term neural and physiological phenotyping of a single human

PubMed Central

Poldrack, Russell A.; Laumann, Timothy O.; Koyejo, Oluwasanmi; Gregory, Brenda; Hover, Ashleigh; Chen, Mei-Yen; Gorgolewski, Krzysztof J.; Luci, Jeffrey; Joo, Sung Jun; Boyd, Ryan L.; Hunicke-Smith, Scott; Simpson, Zack Booth; Caven, Thomas; Sochat, Vanessa; Shine, James M.; Gordon, Evan; Snyder, Abraham Z.; Adeyemo, Babatunde; Petersen, Steven E.; Glahn, David C.; Reese Mckay, D.; Curran, Joanne E.; Göring, Harald H. H.; Carless, Melanie A.; Blangero, John; Dougherty, Robert; Leemans, Alexander; Handwerker, Daniel A.; Frick, Laurie; Marcotte, Edward M.; Mumford, Jeanette A.

2015-01-01

Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders. PMID:26648521

Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders

PubMed Central

Sakai, Kaori; Shoji, Hirotaka; Kohno, Takao; Miyakawa, Tsuyoshi; Hattori, Mitsuharu

2016-01-01

The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder. PMID:27346785

Deep-Brain Stimulation for Basal Ganglia Disorders.

PubMed

Wichmann, Thomas; Delong, Mahlon R

2011-07-01

The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of 'motor' portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the 'limbic' basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders.

Brain hyperconnectivity in children with autism and its links to social deficits.

PubMed

Supekar, Kaustubh; Uddin, Lucina Q; Khouzam, Amirah; Phillips, Jennifer; Gaillard, William D; Kenworthy, Lauren E; Yerys, Benjamin E; Vaidya, Chandan J; Menon, Vinod

2013-11-14

Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting nearly 1 in 88 children, is thought to result from aberrant brain connectivity. Remarkably, there have been no systematic attempts to characterize whole-brain connectivity in children with ASD. Here, we use neuroimaging to show that there are more instances of greater functional connectivity in the brains of children with ASD in comparison to those of typically developing children. Hyperconnectivity in ASD was observed at the whole-brain and subsystems levels, across long- and short-range connections, and was associated with higher levels of fluctuations in regional brain signals. Brain hyperconnectivity predicted symptom severity in ASD, such that children with greater functional connectivity exhibited more severe social deficits. We replicated these findings in two additional independent cohorts, demonstrating again that at earlier ages, the brain of children with ASD is largely functionally hyperconnected in ways that contribute to social dysfunction. Our findings provide unique insights into brain mechanisms underlying childhood autism. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

The neural correlates of obsessive-compulsive disorder: a multimodal perspective.

PubMed

Moreira, P S; Marques, P; Soriano-Mas, C; Magalhães, R; Sousa, N; Soares, J M; Morgado, P

2017-08-29

Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric conditions. An extensive body of the literature has described some of the neurobiological mechanisms underlying the core manifestations of the disorder. Nevertheless, most reports have focused on individual modalities of structural/functional brain alterations, mainly through targeted approaches, thus possibly precluding the power of unbiased exploratory approaches. Eighty subjects (40 OCD and 40 healthy controls) participated in a multimodal magnetic resonance imaging (MRI) investigation, integrating structural and functional data. Voxel-based morphometry analysis was conducted to compare between-group volumetric differences. The whole-brain functional connectome, derived from resting-state functional connectivity (FC), was analyzed with the network-based statistic methodology. Results from structural and functional analysis were integrated in mediation models. OCD patients revealed volumetric reductions in the right superior temporal sulcus. Patients had significantly decreased FC in two distinct subnetworks: the first, involving the orbitofrontal cortex, temporal poles and the subgenual anterior cingulate cortex; the second, comprising the lingual and postcentral gyri. On the opposite, a network formed by connections between thalamic and occipital regions had significantly increased FC in patients. Integrative models revealed direct and indirect associations between volumetric alterations and FC networks. This study suggests that OCD patients display alterations in brain structure and FC, involving complex networks of brain regions. Furthermore, we provided evidence for direct and indirect associations between structural and functional alterations representing complex patterns of interactions between separate brain regions, which may be of upmost relevance for explaining the pathophysiology of the disorder.

The Place of Drugs in the Management of Behavior Disorders after Traumatic Brain Injury.

ERIC Educational Resources Information Center

Rose, Martyn J.

1988-01-01

The article examines the role of drug treatment stressing the need to treat disorders of brain function rather than direct behavior control. Treatment principles concern classification, dosage, monitoring effects, timing of therapy, the distinction between passive and active disorders as well as syndromal, manipulative, ritualistic, cyclothymic,…

Brain State Differentiation and Behavioral Inflexibility in Autism†

PubMed Central

Uddin, Lucina Q.; Supekar, Kaustubh; Lynch, Charles J.; Cheng, Katherine M.; Odriozola, Paola; Barth, Maria E.; Phillips, Jennifer; Feinstein, Carl; Abrams, Daniel A.; Menon, Vinod

2015-01-01

Autism spectrum disorders (ASDs) are characterized by social impairments alongside cognitive and behavioral inflexibility. While social deficits in ASDs have extensively been characterized, the neurobiological basis of inflexibility and its relation to core clinical symptoms of the disorder are unknown. We acquired functional neuroimaging data from 2 cohorts, each consisting of 17 children with ASDs and 17 age- and IQ-matched typically developing (TD) children, during stimulus-evoked brain states involving performance of social attention and numerical problem solving tasks, as well as during intrinsic, resting brain states. Effective connectivity between key nodes of the salience network, default mode network, and central executive network was used to obtain indices of functional organization across evoked and intrinsic brain states. In both cohorts examined, a machine learning algorithm was able to discriminate intrinsic (resting) and evoked (task) functional brain network configurations more accurately in TD children than in children with ASD. Brain state discriminability was related to severity of restricted and repetitive behaviors, indicating that weak modulation of brain states may contribute to behavioral inflexibility in ASD. These findings provide novel evidence for a potential link between neurophysiological inflexibility and core symptoms of this complex neurodevelopmental disorder. PMID:25073720

Neurological soft signs are not "soft" in brain structure and functional networks: evidence from ALE meta-analysis.

PubMed

Zhao, Qing; Li, Zhi; Huang, Jia; Yan, Chao; Dazzan, Paola; Pantelis, Christos; Cheung, Eric F C; Lui, Simon S Y; Chan, Raymond C K

2014-05-01

Neurological soft signs (NSS) are associated with schizophrenia and related psychotic disorders. NSS have been conventionally considered as clinical neurological signs without localized brain regions. However, recent brain imaging studies suggest that NSS are partly localizable and may be associated with deficits in specific brain areas. We conducted an activation likelihood estimation meta-analysis to quantitatively review structural and functional imaging studies that evaluated the brain correlates of NSS in patients with schizophrenia and other psychotic disorders. Six structural magnetic resonance imaging (sMRI) and 15 functional magnetic resonance imaging (fMRI) studies were included. The results from meta-analysis of the sMRI studies indicated that NSS were associated with atrophy of the precentral gyrus, the cerebellum, the inferior frontal gyrus, and the thalamus. The results from meta-analysis of the fMRI studies demonstrated that the NSS-related task was significantly associated with altered brain activation in the inferior frontal gyrus, bilateral putamen, the cerebellum, and the superior temporal gyrus. Our findings from both sMRI and fMRI meta-analyses further support the conceptualization of NSS as a manifestation of the "cerebello-thalamo-prefrontal" brain network model of schizophrenia and related psychotic disorders.

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

Functional network dysfunction in anxiety and anxiety disorders

PubMed Central

Sylvester, C.M.; Corbetta, M.; Raichle, M.E.; Rodebaugh, T.; Schlaggar, B.L.; Sheline, Y.I.; Zorumski, C.F.; Lenze, E.J.

2012-01-01

A recent paradigm shift in systems neuroscience is the division of the human brain into functional networks. Functional networks are collections of brain regions with strongly correlated activity both at rest and during cognitive tasks, and each network is believed to implement a different aspect of cognition. Here, we propose that anxiety disorders and high trait anxiety are associated with a particular pattern of functional network dysfunction: increased functioning of the cingulo-opercular and ventral attention networks as well as decreased functioning of the fronto-parietal and default mode networks. This functional network model can be used to differentiate the pathology of anxiety disorders from other psychiatric illnesses such as major depression and provides targets for novel treatment strategies. PMID:22658924

Functional Evaluation of Hidden Figures Object Analysis in Children with Autistic Disorder

ERIC Educational Resources Information Center

Malisza, Krisztina L.; Clancy, Christine; Shiloff, Deborah; Foreman, Derek; Holden, Jeanette; Jones, Cheryl; Paulson, K.; Summers, Randy; Yu, C. T.; Chudley, Albert E.

2011-01-01

Functional magnetic resonance imaging (fMRI) during performance of a hidden figures task (HFT) was used to compare differences in brain function in children diagnosed with autism disorder (AD) compared to children with attention-deficit/hyperactivity disorder (ADHD) and typical controls (TC). Overall greater functional MRI activity was observed in…

Brain/MINDS: brain-mapping project in Japan

PubMed Central

Okano, Hideyuki; Miyawaki, Atsushi; Kasai, Kiyoto

2015-01-01

There is an emerging interest in brain-mapping projects in countries across the world, including the USA, Europe, Australia and China. In 2014, Japan started a brain-mapping project called Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS). Brain/MINDS aims to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain, and takes advantage of a unique non-human primate animal model, the common marmoset (Callithrix jacchus). In Brain/MINDS, the RIKEN Brain Science Institute acts as a central institute. The objectives of Brain/MINDS can be categorized into the following three major subject areas: (i) structure and functional mapping of a non-human primate brain (the marmoset brain); (ii) development of innovative neurotechnologies for brain mapping; and (iii) human brain mapping; and clinical research. Brain/MINDS researchers are highly motivated to identify the neuronal circuits responsible for the phenotype of neurological and psychiatric disorders, and to understand the development of these devastating disorders through the integration of these three subject areas. PMID:25823872

A selective involvement of putamen functional connectivity in youth with internet gaming disorder.

PubMed

Hong, Soon-Beom; Harrison, Ben J; Dandash, Orwa; Choi, Eun-Jung; Kim, Seong-Chan; Kim, Ho-Hyun; Shim, Do-Hyun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung

2015-03-30

Brain cortico-striatal circuits have consistently been implicated in the pathology of addiction related disorders. We applied a reliable seed-based analysis of the resting-state brain activity to comprehensively delineate the subdivisions of striatal functional connectivity implicated in internet gaming disorder. Among twelve right-handed male adolescents with internet gaming disorder and 11 right-handed and gender-matched healthy controls, we examined group differences in the functional connectivity of dorsal and ventral subdivisions of the caudate nucleus and putamen, as well as the association of these connectivity indices with behavioral measures of internet use. Adolescents with internet gaming disorder showed significantly reduced dorsal putamen functional connectivity with the posterior insula-parietal operculum. More time spent playing online games predicted significantly greater functional connectivity between the dorsal putamen and bilateral primary somatosensory cortices in adolescents with internet gaming disorder, and significantly lower functional connectivity between the dorsal putamen and bilateral sensorimotor cortices in healthy controls. The dorsal putamen functional connectivity was significantly and specifically different in adolescents with internet gaming disorder. The findings suggest a possible biomarker of internet gaming disorder. Copyright © 2015. Published by Elsevier B.V.

Advances in Electrophysiological Research

PubMed Central

Kamarajan, Chella; Porjesz, Bernice

2015-01-01

Electrophysiological measures of brain function are effective tools to understand neurocognitive phenomena and sensitive indicators of pathophysiological processes associated with various clinical conditions, including alcoholism. Individuals with alcohol use disorder (AUD) and their high-risk offspring have consistently shown dysfunction in several electrophysiological measures in resting state (i.e., electroencephalogram) and during cognitive tasks (i.e., event-related potentials and event-related oscillations). Researchers have recently developed sophisticated signal-processing techniques to characterize different aspects of brain dynamics, which can aid in identifying the neural mechanisms underlying alcoholism and other related complex disorders. These quantitative measures of brain function also have been successfully used as endophenotypes to identify and help understand genes associated with AUD and related disorders. Translational research also is examining how brain electrophysiological measures potentially can be applied to diagnosis, prevention, and treatment. PMID:26259089

Progress and roadblocks in the search for brain-based biomarkers of autism and attention-deficit/hyperactivity disorder.

PubMed

Uddin, L Q; Dajani, D R; Voorhies, W; Bednarz, H; Kana, R K

2017-08-22

Children with neurodevelopmental disorders benefit most from early interventions and treatments. The development and validation of brain-based biomarkers to aid in objective diagnosis can facilitate this important clinical aim. The objective of this review is to provide an overview of current progress in the use of neuroimaging to identify brain-based biomarkers for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), two prevalent neurodevelopmental disorders. We summarize empirical work that has laid the foundation for using neuroimaging to objectively quantify brain structure and function in ways that are beginning to be used in biomarker development, noting limitations of the data currently available. The most successful machine learning methods that have been developed and applied to date are discussed. Overall, there is increasing evidence that specific features (for example, functional connectivity, gray matter volume) of brain regions comprising the salience and default mode networks can be used to discriminate ASD from typical development. Brain regions contributing to successful discrimination of ADHD from typical development appear to be more widespread, however there is initial evidence that features derived from frontal and cerebellar regions are most informative for classification. The identification of brain-based biomarkers for ASD and ADHD could potentially assist in objective diagnosis, monitoring of treatment response and prediction of outcomes for children with these neurodevelopmental disorders. At present, however, the field has yet to identify reliable and reproducible biomarkers for these disorders, and must address issues related to clinical heterogeneity, methodological standardization and cross-site validation before further progress can be achieved.

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

Typical and atypical brain development: a review of neuroimaging studies

PubMed Central

Dennis, Emily L.; Thompson, Paul M.

2013-01-01

In the course of development, the brain undergoes a remarkable process of restructuring as it adapts to the environment and becomes more efficient in processing information. A variety of brain imaging methods can be used to probe how anatomy, connectivity, and function change in the developing brain. Here we review recent discoveries regarding these brain changes in both typically developing individuals and individuals with neurodevelopmental disorders. We begin with typical development, summarizing research on changes in regional brain volume and tissue density, cortical thickness, white matter integrity, and functional connectivity. Space limits preclude the coverage of all neurodevelopmental disorders; instead, we cover a representative selection of studies examining neural correlates of autism, attention deficit/hyperactivity disorder, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Down syndrome, and Turner syndrome. Where possible, we focus on studies that identify an age by diagnosis interaction, suggesting an altered developmental trajectory. The studies we review generally cover the developmental period from infancy to early adulthood. Great progress has been made over the last 20 years in mapping how the brain matures with MR technology. With ever-improving technology, we expect this progress to accelerate, offering a deeper understanding of brain development, and more effective interventions for neurodevelopmental disorders. PMID:24174907

Typical and atypical brain development: a review of neuroimaging studies.

PubMed

Dennis, Emily L; Thompson, Paul M

2013-09-01

In the course of development, the brain undergoes a remarkable process of restructuring as it adapts to the environment and becomes more efficient in processing information. A variety of brain imaging methods can be used to probe how anatomy, connectivity, and function change in the developing brain. Here we review recent discoveries regarding these brain changes in both typically developing individuals and individuals with neurodevelopmental disorders. We begin with typical development, summarizing research on changes in regional brain volume and tissue density, cortical thickness, white matter integrity, and functional connectivity. Space limits preclude the coverage of all neurodevelopmental disorders; instead, we cover a representative selection of studies examining neural correlates of autism, attention deficit/hyperactivity disorder, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Down syndrome, and Turner syndrome. Where possible, we focus on studies that identify an age by diagnosis interaction, suggesting an altered developmental trajectory. The studies we review generally cover the developmental period from infancy to early adulthood. Great progress has been made over the last 20 years in mapping how the brain matures with MR technology. With ever-improving technology, we expect this progress to accelerate, offering a deeper understanding of brain development, and more effective interventions for neurodevelopmental disorders.

Association of familial risk for schizophrenia with thalamic and medial prefrontal functional connectivity during attentional control.

PubMed

Antonucci, Linda A; Taurisano, Paolo; Fazio, Leonardo; Gelao, Barbara; Romano, Raffaella; Quarto, Tiziana; Porcelli, Annamaria; Mancini, Marina; Di Giorgio, Annabella; Caforio, Grazia; Pergola, Giulio; Popolizio, Teresa; Bertolino, Alessandro; Blasi, Giuseppe

2016-05-01

Anomalies in behavioral correlates of attentional processing and related brain activity are crucial correlates of schizophrenia and associated with familial risk for this brain disorder. However, it is not clear how brain functional connectivity during attentional processes is key for schizophrenia and linked with trait vs. state related variables. To address this issue, we investigated patterns of functional connections during attentional control in healthy siblings of patients with schizophrenia, who share with probands genetic features but not variables related to the state of the disorder. 356 controls, 55 patients with schizophrenia on stable treatment with antipsychotics and 40 healthy siblings of patients with this brain disorder underwent the Variable Attentional Control (VAC) task during fMRI. Independent Component Analysis (ICA) is allowed to identify independent components (IC) of BOLD signal recorded during task performance. Results indicated reduced connectivity strength in patients with schizophrenia as well as in their healthy siblings in left thalamus within an attentional control component and greater connectivity in right medial prefrontal cortex (PFC) within the so-called Default Mode Network (DMN) compared to healthy individuals. These results suggest a relationship between familial risk for schizophrenia and brain functional networks during attentional control, such that this biological phenotype may be considered a useful intermediate phenotype in order to link genes effects to aspects of the pathophysiology of this brain disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

The functional neuroanatomy of bipolar disorder: a consensus model

PubMed Central

Strakowski, Stephen M; Adler, Caleb M; Almeida, Jorge; Altshuler, Lori L; Blumberg, Hilary P; Chang, Kiki D; DelBello, Melissa P; Frangou, Sophia; McIntosh, Andrew; Phillips, Mary L; Sussman, Jessika E; Townsend, Jennifer D

2013-01-01

Objectives Functional neuroimaging methods have proliferated in recent years, such that functional magnetic resonance imaging, in particular, is now widely used to study bipolar disorder. However, discrepant findings are common. A workgroup was organized by the Department of Psychiatry, University of Cincinnati (Cincinnati, OH, USA) to develop a consensus functional neuroanatomic model of bipolar I disorder based upon the participants’ work as well as that of others. Methods Representatives from several leading bipolar disorder neuroimaging groups were organized to present an overview of their areas of expertise as well as focused reviews of existing data. The workgroup then developed a consensus model of the functional neuroanatomy of bipolar disorder based upon these data. Results Among the participants, a general consensus emerged that bipolar I disorder arises from abnormalities in the structure and function of key emotional control networks in the human brain. Namely, disruption in early development (e.g., white matter connectivity, prefrontal pruning) within brain networks that modulate emotional behavior leads to decreased connectivity among ventral prefrontal networks and limbic brain regions, especially amygdala. This developmental failure to establish healthy ventral prefrontal–limbic modulation underlies the onset of mania and ultimately, with progressive changes throughout these networks over time and with affective episodes, a bipolar course of illness. Conclusions This model provides a potential substrate to guide future investigations and areas needing additional focus are identified. PMID:22631617

The Role of Intrinsic Brain Functional Connectivity in Vulnerability and Resilience to Bipolar Disorder.

PubMed

Doucet, Gaelle E; Bassett, Danielle S; Yao, Nailin; Glahn, David C; Frangou, Sophia

2017-12-01

Bipolar disorder is a heritable disorder characterized by mood dysregulation associated with brain functional dysconnectivity. Previous research has focused on the detection of risk- and disease-associated dysconnectivity in individuals with bipolar disorder and their first-degree relatives. The present study seeks to identify adaptive brain connectivity features associated with resilience, defined here as avoidance of illness or delayed illness onset in unaffected siblings of patients with bipolar disorder. Graph theoretical methods were used to examine global and regional brain network topology in head-motion-corrected resting-state functional MRI data acquired from 78 patients with bipolar disorder, 64 unaffected siblings, and 41 healthy volunteers. Global network properties were preserved in patients and their siblings while both groups showed reductions in the cohesiveness of the sensorimotor network. In the patient group, these sensorimotor network abnormalities were coupled with reduced integration of core default mode network regions in the ventromedial cortex and hippocampus. Conversely, integration of the default mode network was increased in the sibling group compared with both the patient group and the healthy volunteer group. The authors found that trait-related vulnerability to bipolar disorder was associated with reduced resting-state cohesiveness of the sensorimotor network in patients with bipolar disorder. However, integration of the default mode network emerged as a key feature differentiating disease expression and resilience between the patients and their siblings. This is indicative of the presence of neural mechanisms that may promote resilience, or at least delay illness onset.

Global brain connectivity alterations in patients with schizophrenia and bipolar spectrum disorders.

PubMed

Skåtun, Kristina C; Kaufmann, Tobias; Tønnesen, Siren; Biele, Guido; Melle, Ingrid; Agartz, Ingrid; Alnæs, Dag; Andreassen, Ole A; Westlye, Lars T

2016-08-01

The human brain is organized into functionally distinct modules of which interactions constitute the human functional connectome. Accumulating evidence has implicated perturbations in the patterns of brain connectivity across a range of neurologic and neuropsychiatric disorders, but little is known about diagnostic specificity. Schizophrenia and bipolar disorders are severe mental disorders with partly overlapping symptomatology. Neuroimaging has demonstrated brain network disintegration in the pathophysiologies; however, to which degree the 2 diagnoses present with overlapping abnormalities remains unclear. We collected resting-state fMRI data from patients with schizophrenia or bipolar disorder and from healthy controls. Aiming to characterize connectivity differences across 2 severe mental disorders, we derived global functional connectivity using eigenvector centrality mapping, which allows for regional inference of centrality or importance in the brain network. Seventy-one patients with schizophrenia, 43 with bipolar disorder and 196 healthy controls participated in our study. We found significant effects of diagnosis in 12 clusters, where pairwise comparisons showed decreased global connectivity in high-centrality clusters: sensory regions in patients with schizophrenia and subcortical regions in both patient groups. Increased connectivity occurred in frontal and parietal clusters in patients with schizophrenia, with intermediate effects in those with bipolar disorder. Patient groups differed in most cortical clusters, with the strongest effects in sensory regions. Methodological concerns of in-scanner motion and the use of full correlation measures may make analyses more vulnerable to noise. Our results show decreased eigenvector centrality of limbic structures in both patient groups and in sensory regions in patients with schizophrenia as well as increased centrality in frontal and parietal regions in both groups, with stronger effects in patients with schizophrenia.

Corticostriatal Connectivity in Antisocial Personality Disorder by MAO-A Genotype and Its Relationship to Aggressive Behavior.

PubMed

Kolla, Nathan J; Dunlop, Katharine; Meyer, Jeffrey H; Downar, Jonathan

2018-05-09

The influence of genetic variation on resting-state neural networks represents a burgeoning line of inquiry in psychiatric research. Monoamine oxidase A, an X-linked gene, is one example of a molecular target linked to brain activity in psychiatric illness. Monoamine oxidase A genetic variants, including the high and low variable nucleotide tandem repeat polymorphisms, have been shown to differentially affect brain functional connectivity in healthy humans. However, it is currently unknown whether these same polymorphisms influence resting-state brain activity in clinical conditions. Given its high burden on society and strong connection to violent behavior, antisocial personality disorder is a logical condition to study, since in vivo markers of monoamine oxidase A brain enzyme are reduced in key affect-modulating regions, and striatal levels of monoamine oxidase A show a relation with the functional connectivity of this same region. We utilized monoamine oxidase A genotyping and seed-to-voxel-based functional connectivity to investigate the relationship between genotype and corticostriatal connectivity in 21 male participants with severe antisocial personality disorder and 19 male healthy controls. Dorsal striatal connectivity to the frontal pole and anterior cingulate gyrus differentiated antisocial personality disorder subjects and healthy controls by monoamine oxidase A genotype. Furthermore, the linear relationship of proactive aggression to superior ventral striatal-angular gyrus functional connectivity differed by monoamine oxidase A genotype in the antisocial personality disorder groups. These results suggest that monoamine oxidase A genotype may affect corticostriatal connectivity in antisocial personality disorder and that these functional connections may also underlie use of proactive aggression in a genotype-specific manner.

Deep-Brain Stimulation for Basal Ganglia Disorders

PubMed Central

Wichmann, Thomas; DeLong, Mahlon R.

2011-01-01

The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of ‘motor’ portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the ‘limbic’ basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders. PMID:21804953

Translational potential of astrocytes in brain disorders

PubMed Central

Verkhratsky, Alexei; Steardo, Luca; Montana, Vedrana

2015-01-01

Fundamentally, all brain disorders can be broadly defined as the homeostatic failure of this organ. As the brain is composed of many different cells types, including but not limited to neurons and glia, it is only logical that all the cell types/constituents could play a role in health and disease. Yet, for a long time the sole conceptualization of brain pathology was focused on the well-being of neurons. Here, we challenge this neuron-centric view and present neuroglia as a key element in neuropathology, a process that has a toll on astrocytes, which undergo complex morpho-functional changes that can in turn affect the course of the disorder. Such changes can be grossly identified as reactivity, atrophy with loss of function and pathological remodeling. We outline the pathogenic potential of astrocytes in variety of disorders, ranging from neurotrauma, infection, toxic damage, stroke, epilepsy, neurodevelopmental, neurodegenerative and psychiatric disorders, Alexander disease to neoplastic changes seen in gliomas. We hope that in near future we would witness glial-based translational medicine with generation of deliverables for the containment and cure of disorders. We point out that such as a task will require a holistic and multi-disciplinary approach that will take in consideration the concerted operation of all the cell types in the brain. PMID:26386136

Functional characteristics of the brain in college students with internet gaming disorder.

PubMed

Liu, Jun; Li, Weihui; Zhou, Shunke; Zhang, Li; Wang, Zhiyuan; Zhang, Yan; Jiang, Yebin; Li, Lingjiang

2016-03-01

Internet gaming disorder (IGD) is a subtype of internet addiction disorder (IAD), but its pathogenesis remains unclear. This study investigated brain function in IGD individuals using task-state functional magnetic resonance imaging (fMRI). It is a prospective study in 19 IGD individuals and 19 matched healthy controls. They all received internet videogame stimuli while a 3.0 T fMRI was used to assess echo planar imaging. Brain activity was analyzed using the Brain Voyager software package. Functional data were spatially smoothed using Gaussian kernel. The threshold level was positioned at 10 pixels, and the activation range threshold was set to 10 voxels. Activated brain regions were compared between the two groups, as well as the amount of activated voxels. The internet videogame stimuli activated brain regions in both groups. Compared with controls, the IGD group showed increased activation in the right superior parietal lobule, right insular lobe, right precuneus, right cingulated gyrus, right superior temporal gyrus, and left brainstem. There was a significant difference in the number of activated voxels between the two groups. An average of 1078 voxels was activated in the IGD group compared with only 232 in the control group. Internet videogame play activates the vision, space, attention, and execution centers located in the occipital, temporal, parietal, and frontal gyri. Abnormal brain function was noted in IGD subjects, with hypofunction of the frontal cortex. IGD subjects showed laterality activation of the right cerebral hemisphere.

Machine learning classifier using abnormal brain network topological metrics in major depressive disorder.

PubMed

Guo, Hao; Cao, Xiaohua; Liu, Zhifen; Li, Haifang; Chen, Junjie; Zhang, Kerang

2012-12-05

Resting state functional brain networks have been widely studied in brain disease research. However, it is currently unclear whether abnormal resting state functional brain network metrics can be used with machine learning for the classification of brain diseases. Resting state functional brain networks were constructed for 28 healthy controls and 38 major depressive disorder patients by thresholding partial correlation matrices of 90 regions. Three nodal metrics were calculated using graph theory-based approaches. Nonparametric permutation tests were then used for group comparisons of topological metrics, which were used as classified features in six different algorithms. We used statistical significance as the threshold for selecting features and measured the accuracies of six classifiers with different number of features. A sensitivity analysis method was used to evaluate the importance of different features. The result indicated that some of the regions exhibited significantly abnormal nodal centralities, including the limbic system, basal ganglia, medial temporal, and prefrontal regions. Support vector machine with radial basis kernel function algorithm and neural network algorithm exhibited the highest average accuracy (79.27 and 78.22%, respectively) with 28 features (P<0.05). Correlation analysis between feature importance and the statistical significance of metrics was investigated, and the results revealed a strong positive correlation between them. Overall, the current study demonstrated that major depressive disorder is associated with abnormal functional brain network topological metrics and statistically significant nodal metrics can be successfully used for feature selection in classification algorithms.

Brain differences between persistent and remitted attention deficit hyperactivity disorder.

PubMed

Mattfeld, Aaron T; Gabrieli, John D E; Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Kotte, Amelia; Kagan, Elana; Whitfield-Gabrieli, Susan

2014-09-01

Previous resting state studies examining the brain basis of attention deficit hyperactivity disorder have not distinguished between patients who persist versus those who remit from the diagnosis as adults. To characterize the neurobiological differences and similarities of persistence and remittance, we performed resting state functional magnetic resonance imaging in individuals who had been longitudinally and uniformly characterized as having or not having attention deficit hyperactivity disorder in childhood and again in adulthood (16 years after baseline assessment). Intrinsic functional brain organization was measured in patients who had a persistent diagnosis in childhood and adulthood (n = 13), in patients who met diagnosis in childhood but not in adulthood (n = 22), and in control participants who never had attention deficit hyperactivity disorder (n = 17). A positive functional correlation between posterior cingulate and medial prefrontal cortices, major components of the default-mode network, was reduced only in patients whose diagnosis persisted into adulthood. A negative functional correlation between medial and dorsolateral prefrontal cortices was reduced in both persistent and remitted patients. The neurobiological dissociation between the persistence and remittance of attention deficit hyperactivity disorder may provide a framework for the relation between the clinical diagnosis, which indicates the need for treatment, and additional deficits that are common, such as executive dysfunctions. © 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.

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.

Age-associated changes in rich-club organisation in autistic and neurotypical human brains

PubMed Central

Watanabe, Takamitsu; Rees, Geraint

2015-01-01

Macroscopic structural networks in the human brain have a rich-club architecture comprising both highly inter-connected central regions and sparsely connected peripheral regions. Recent studies show that disruption of this functionally efficient organisation is associated with several psychiatric disorders. However, despite increasing attention to this network property, whether age-associated changes in rich-club organisation occur during human adolescence remains unclear. Here, analysing a publicly shared diffusion tensor imaging dataset, we found that, during adolescence, brains of typically developing (TD) individuals showed increases in rich-club organisation and inferred network functionality, whereas individuals with autism spectrum disorders (ASD) did not. These differences between TD and ASD groups were statistically significant for both structural and functional properties. Moreover, this typical age-related changes in rich-club organisation were characterised by progressive involvement of the right anterior insula. In contrast, in ASD individuals, did not show typical increases in grey matter volume, and this relative anatomical immaturity was correlated with the severity of ASD social symptoms. These results provide evidence that rich-club architecture is one of the bases of functionally efficient brain networks underpinning complex cognitive functions in adult human brains. Furthermore, our findings suggest that immature rich-club organisation might be associated with some neurodevelopmental disorders. PMID:26537477

[Effectiveness of music in brain rehabilitation. A systematic review].

PubMed

Sihvonen, Aleksi J; Leo, Vera; Särkämö, Teppo; Soinila, Seppo

2014-01-01

There is no curative treatment for diseases causing brain injury. Music causes extensive activation of the brain, promoting the repair of neural systems. Addition of music listening to rehabilitation enhances the regulation or motor functions in Parkinson and stroke patients, accelerates the recovery of speech disorder and cognitive injuries after stroke, and decreases the behavioral disorders of dementia patients. Music enhances the ability to concentrate and decreases mental confusion. The effect of music can also be observed as structural and functional changes of the brain. The effect is based, among other things, on lessening of physiologic stress and depression and on activation of the dopaminergic mesolimbic system.

Aberrant Spontaneous and Task-Dependent Functional Connections in the Anxious Brain

PubMed Central

MacNamara, Annmarie; DiGangi, Julia; Phan, K. Luan

2016-01-01

A number of brain regions have been implicated in the anxiety disorders, yet none of these regions in isolation has been distinguished as the sole or discrete site responsible for anxiety disorder pathology. Therefore, the identification of dysfunctional neural networks as represented by alterations in the temporal correlation of blood-oxygen level dependent (BOLD) signal across several brain regions in anxiety disorders has been increasingly pursued in the past decade. Here, we review task-independent (e.g., resting state) and task-induced functional connectivity magnetic resonance imaging (fcMRI) studies in the adult anxiety disorders (including trauma- and stressor-related and obsessive compulsive disorders). The results of this review suggest that anxiety disorder pathophysiology involves aberrant connectivity between amygdala-frontal and frontal-striatal regions, as well as within and between canonical “intrinsic” brain networks - the default mode and salience networks, and that evidence of these aberrations may help inform findings of regional activation abnormalities observed in the anxiety disorders. Nonetheless, significant challenges remain, including the need to better understand mixed findings observed using different methods (e.g., resting state and task-based approaches); the need for more developmental work; the need to delineate disorder-specific and transdiagnostic fcMRI aberrations in the anxiety disorders; and the need to better understand the clinical significance of fcMRI abnormalities. In meeting these challenges, future work has the potential to elucidate aberrant neural networks as intermediate, brain-based phenotypes to predict disease onset and progression, refine diagnostic nosology, and ascertain treatment mechanisms and predictors of treatment response across anxiety, trauma-related and obsessive compulsive disorders. PMID:27141532

Joint Attention and Brain Functional Connectivity in Infants and Toddlers.

PubMed

Eggebrecht, Adam T; Elison, Jed T; Feczko, Eric; Todorov, Alexandre; Wolff, Jason J; Kandala, Sridhar; Adams, Chloe M; Snyder, Abraham Z; Lewis, John D; Estes, Annette M; Zwaigenbaum, Lonnie; Botteron, Kelly N; McKinstry, Robert C; Constantino, John N; Evans, Alan; Hazlett, Heather C; Dager, Stephen; Paterson, Sarah J; Schultz, Robert T; Styner, Martin A; Gerig, Guido; Das, Samir; Kostopoulos, Penelope; Schlaggar, Bradley L; Petersen, Steven E; Piven, Joseph; Pruett, John R

2017-03-01

Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development. © The Author 2017. Published by Oxford University Press.

Joint Attention and Brain Functional Connectivity in Infants and Toddlers

PubMed Central

Eggebrecht, Adam T.; Elison, Jed T.; Feczko, Eric; Todorov, Alexandre; Wolff, Jason J.; Kandala, Sridhar; Adams, Chloe M.; Snyder, Abraham Z.; Lewis, John D.; Estes, Annette M.; Zwaigenbaum, Lonnie; Botteron, Kelly N.; McKinstry, Robert C.; Constantino, John N.; Evans, Alan; Hazlett, Heather C.; Dager, Stephen; Paterson, Sarah J.; Schultz, Robert T.; Styner, Martin A.; Gerig, Guido; Das, Samir; Kostopoulos, Penelope; Schlaggar, Bradley L.; Petersen, Steven E.; Piven, Joseph; Pruett, John R.

2017-01-01

Abstract Initiating joint attention (IJA), the behavioral instigation of coordinated focus of 2 people on an object, emerges over the first 2 years of life and supports social-communicative functioning related to the healthy development of aspects of language, empathy, and theory of mind. Deficits in IJA provide strong early indicators for autism spectrum disorder, and therapies targeting joint attention have shown tremendous promise. However, the brain systems underlying IJA in early childhood are poorly understood, due in part to significant methodological challenges in imaging localized brain function that supports social behaviors during the first 2 years of life. Herein, we show that the functional organization of the brain is intimately related to the emergence of IJA using functional connectivity magnetic resonance imaging and dimensional behavioral assessments in a large semilongitudinal cohort of infants and toddlers. In particular, though functional connections spanning the brain are involved in IJA, the strongest brain-behavior associations cluster within connections between a small subset of functional brain networks; namely between the visual network and dorsal attention network and between the visual network and posterior cingulate aspects of the default mode network. These observations mark the earliest known description of how functional brain systems underlie a burgeoning fundamental social behavior, may help improve the design of targeted therapies for neurodevelopmental disorders, and, more generally, elucidate physiological mechanisms essential to healthy social behavior development. PMID:28062515

Mind, brain, and personality disorders.

PubMed

Gabbard, Glen O

2005-04-01

The use of the terms "mind" and "brain" in psychiatry is often associated with a set of polarities. Concepts such as environment, psychosocial, and psychotherapy are linked with "mind," while genes, biology, and medication are often associated with "brain." The author examines these dichotomies as they apply to personality disorders. Research on antisocial and borderline personality disorders that is relevant to these dichotomies is evaluated. The implications of the findings for the understanding of pathogenesis and treatment are reconsidered. In the clinical setting, it is problematic to lump together terms such as "genes," "brain," and "biological" as though they are separate and distinct from terms such as "environment," "mind," and "psychosocial." These dichotomies are problematic, because genes and environment are inextricably intertwined in the pathogenesis of personality disorders, psychosocial experiences may result in permanent changes in the brain, and psychotherapy may have its effect by altering brain structure and function. The "theory of mind" is a useful construct for bridging "mind" and "brain" in the treatment of personality disorders. Severe personality disorders are best understood and treated without "either-or" dichotomies of brain and mind. Each domain has a different language, however, and the language of the mind is necessary to help the patient develop a theory of mind.

Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

PubMed

Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

2017-07-04

This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders.

PubMed

Kaminsky, Natalie; Bihari, Ofer; Kanner, Sivan; Barzilai, Ari

2016-06-01

The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a "hostile" environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit. Copyright © 2016 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

Reduced Prefrontal Hemodynamic Response in Pediatric Obsessive-Compulsive Disorder as Measured by Near-Infrared Spectroscopy

ERIC Educational Resources Information Center

Ota, Toyosaku; Iida, Junzo; Sawada, Masayuki; Suehiro, Yuko; Yamamuro, Kazuhiko; Matsuura, Hiroki; Tanaka, Shohei; Kishimoto, Naoko; Negoro, Hideki; Kishimoto, Toshifumi

2013-01-01

Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders. Functional neuroimaging studies of patients with obsessive-compulsive disorder (OCD) have suggested that the frontal cortex and subcortical structures may play a role in the pathophysiology of the disorder.…

Integrating Functional Brain Neuroimaging and Developmental Cognitive Neuroscience in Child Psychiatry Research

ERIC Educational Resources Information Center

Pavuluri, Mani N.; Sweeney, John A.

2008-01-01

The use of cognitive neuroscience and functional brain neuroimaging to understand brain dysfunction in pediatric psychiatric disorders is discussed. Results show that bipolar youths demonstrate impairment in affective and cognitive neural systems and in these two circuits' interface. Implications for the diagnosis and treatment of psychiatric…

Topologically convergent and divergent functional connectivity patterns in unmedicated unipolar depression and bipolar disorder.

PubMed

Wang, Y; Wang, J; Jia, Y; Zhong, S; Zhong, M; Sun, Y; Niu, M; Zhao, L; Zhao, L; Pan, J; Huang, L; Huang, R

2017-07-04

Bipolar disorder (BD), particularly BD II, is frequently misdiagnosed as unipolar depression (UD), leading to inappropriate treatment and poor clinical outcomes. Although depressive symptoms may be expressed similarly in UD and BD, the similarities and differences in the architecture of brain functional networks between the two disorders are still unknown. In this study, we hypothesized that UD and BD II patients would show convergent and divergent patterns of disrupted topological organization of the functional connectome, especially in the default mode network (DMN) and the limbic network. Brain resting-state functional magnetic resonance imaging (fMRI) data were acquired from 32 UD-unmedicated patients, 31 unmedicated BD II patients (current episode depressed) and 43 healthy subjects. Using graph theory, we systematically studied the topological organization of their whole-brain functional networks at the following three levels: whole brain, modularity and node. First, both the UD and BD II patients showed increased characteristic path length and decreased global efficiency compared with the controls. Second, both the UD and BD II patients showed disrupted intramodular connectivity within the DMN and limbic system network. Third, decreased nodal characteristics (nodal strength and nodal efficiency) were found predominantly in brain regions in the DMN, limbic network and cerebellum of both the UD and BD II patients, whereas differences between the UD and BD II patients in the nodal characteristics were also observed in the precuneus and temporal pole. Convergent deficits in the topological organization of the whole brain, DMN and limbic networks may reflect overlapping pathophysiological processes in unipolar and bipolar depression. Our discovery of divergent regional connectivity that supports emotion processing could help to identify biomarkers that will aid in differentiating these disorders.

Topologically convergent and divergent functional connectivity patterns in unmedicated unipolar depression and bipolar disorder

PubMed Central

Wang, Y; Wang, J; Jia, Y; Zhong, S; Zhong, M; Sun, Y; Niu, M; Zhao, L; Zhao, L; Pan, J; Huang, L; Huang, R

2017-01-01

Bipolar disorder (BD), particularly BD II, is frequently misdiagnosed as unipolar depression (UD), leading to inappropriate treatment and poor clinical outcomes. Although depressive symptoms may be expressed similarly in UD and BD, the similarities and differences in the architecture of brain functional networks between the two disorders are still unknown. In this study, we hypothesized that UD and BD II patients would show convergent and divergent patterns of disrupted topological organization of the functional connectome, especially in the default mode network (DMN) and the limbic network. Brain resting-state functional magnetic resonance imaging (fMRI) data were acquired from 32 UD-unmedicated patients, 31 unmedicated BD II patients (current episode depressed) and 43 healthy subjects. Using graph theory, we systematically studied the topological organization of their whole-brain functional networks at the following three levels: whole brain, modularity and node. First, both the UD and BD II patients showed increased characteristic path length and decreased global efficiency compared with the controls. Second, both the UD and BD II patients showed disrupted intramodular connectivity within the DMN and limbic system network. Third, decreased nodal characteristics (nodal strength and nodal efficiency) were found predominantly in brain regions in the DMN, limbic network and cerebellum of both the UD and BD II patients, whereas differences between the UD and BD II patients in the nodal characteristics were also observed in the precuneus and temporal pole. Convergent deficits in the topological organization of the whole brain, DMN and limbic networks may reflect overlapping pathophysiological processes in unipolar and bipolar depression. Our discovery of divergent regional connectivity that supports emotion processing could help to identify biomarkers that will aid in differentiating these disorders. PMID:28675389

Psychotropic medication, psychiatric disorders, and higher brain functions

PubMed Central

Schulz, Pierre; Steimer, Thierry

2000-01-01

Conventional psychiatric diagnosis is founded on symptom description; this then governs the choice of psychotropic medication. This purely descriptive approach resembles a description of diphtheria from the premicrobiology era. Based on current advances in basic and clinical neuroscience, we propose inserting an intermediate level of analysis between psychiatric symptoms and pharmacologic modes of action. Paradigm 1 is to analyze psychiatric symptoms in terms of which higher brain function(s) is (are) abnormal, ie, symptoms should be analyzed as higher brain dysfunction: a case study in obsessive-compulsive disorder reveals pointers in four common symptoms to the higher functions of working memory, emotional overlay, absence of voluntary control, and the ability to evaluate personal mental phenomena. Paradigm 2 is to view psychotropic drugs as modifying normal higher brain functions, rather than merely treating symptoms, which they do only secondarily: thus depression may respond to agents that act on related aspects of mental life derived from higher brain functions, eg, the ability to enhance bonding. We advocate a strategy in which psychiatric illness is progressively reclassified through knowledge in clinical neuroscience and treatment targets are revised accordingly. PMID:22034249

Omics analysis of mouse brain models of human diseases.

PubMed

Paban, Véronique; Loriod, Béatrice; Villard, Claude; Buee, Luc; Blum, David; Pietropaolo, Susanna; Cho, Yoon H; Gory-Faure, Sylvie; Mansour, Elodie; Gharbi, Ali; Alescio-Lautier, Béatrice

2017-02-05

The identification of common gene/protein profiles related to brain alterations, if they exist, may indicate the convergence of the pathogenic mechanisms driving brain disorders. Six genetically engineered mouse lines modelling neurodegenerative diseases and neuropsychiatric disorders were considered. Omics approaches, including transcriptomic and proteomic methods, were used. The gene/protein lists were used for inter-disease comparisons and further functional and network investigations. When the inter-disease comparison was performed using the gene symbol identifiers, the number of genes/proteins involved in multiple diseases decreased rapidly. Thus, no genes/proteins were shared by all 6 mouse models. Only one gene/protein (Gfap) was shared among 4 disorders, providing strong evidence that a common molecular signature does not exist among brain diseases. The inter-disease comparison of functional processes showed the involvement of a few major biological processes indicating that brain diseases of diverse aetiologies might utilize common biological pathways in the nervous system, without necessarily involving similar molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional neuroanatomy of disorders of consciousness.

PubMed

Di Perri, Carol; Stender, Johan; Laureys, Steven; Gosseries, Olivia

2014-01-01

Our understanding of the mechanisms of loss and recovery of consciousness, following severe brain injury or during anesthesia, is changing rapidly. Recent neuroimaging studies have shown that patients with chronic disorders of consciousness and subjects undergoing general anesthesia present a complex dysfunctionality in the architecture of brain connectivity. At present, the global hallmark of impaired consciousness appears to be a multifaceted dysfunctional connectivity pattern with both within-network loss of connectivity in a widespread frontoparietal network and between-network hyperconnectivity involving other regions such as the insula and ventral tegmental area. Despite ongoing efforts, the mechanisms underlying the emergence of consciousness after severe brain injury are not thoroughly understood. Important questions remain unanswered: What triggers the connectivity impairment leading to disorders of consciousness? Why do some patients recover from coma, while others with apparently similar brain injuries do not? Understanding these mechanisms could lead to a better comprehension of brain function and, hopefully, lead to new therapeutic strategies in this challenging patient population. © 2013.

Brain damage and behavioural disorders in fish induced by plastic nanoparticles delivered through the food chain.

PubMed

Mattsson, Karin; Johnson, Elyse V; Malmendal, Anders; Linse, Sara; Hansson, Lars-Anders; Cedervall, Tommy

2017-09-13

The tremendous increases in production of plastic materials has led to an accumulation of plastic pollution worldwide. Many studies have addressed the physical effects of large-sized plastics on organisms, whereas few have focused on plastic nanoparticles, despite their distinct chemical, physical and mechanical properties. Hence our understanding of their effects on ecosystem function, behaviour and metabolism of organisms remains elusive. Here we demonstrate that plastic nanoparticles reduce survival of aquatic zooplankton and penetrate the blood-to-brain barrier in fish and cause behavioural disorders. Hence, for the first time, we uncover direct interactions between plastic nanoparticles and brain tissue, which is the likely mechanism behind the observed behavioural disorders in the top consumer. In a broader perspective, our findings demonstrate that plastic nanoparticles are transferred up through a food chain, enter the brain of the top consumer and affect its behaviour, thereby severely disrupting the function of natural ecosystems.

Similar Brain Activation during False Belief Tasks in a Large Sample of Adults with and without Autism

PubMed Central

Dufour, Nicholas; Redcay, Elizabeth; Young, Liane; Mavros, Penelope L.; Moran, Joseph M.; Triantafyllou, Christina; Gabrieli, John D. E.; Saxe, Rebecca

2013-01-01

Reading about another person’s beliefs engages ‘Theory of Mind’ processes and elicits highly reliable brain activation across individuals and experimental paradigms. Using functional magnetic resonance imaging, we examined activation during a story task designed to elicit Theory of Mind processing in a very large sample of neurotypical (N = 462) individuals, and a group of high-functioning individuals with autism spectrum disorders (N = 31), using both region-of-interest and whole-brain analyses. This large sample allowed us to investigate group differences in brain activation to Theory of Mind tasks with unusually high sensitivity. There were no differences between neurotypical participants and those diagnosed with autism spectrum disorder. These results imply that the social cognitive impairments typical of autism spectrum disorder can occur without measurable changes in the size, location or response magnitude of activity during explicit Theory of Mind tasks administered to adults. PMID:24073267

The FMRP regulon: from targets to disease convergence

PubMed Central

Fernández, Esperanza; Rajan, Nicholas; Bagni, Claudia

2013-01-01

The fragile X mental retardation protein (FMRP) is an RNA-binding protein that regulates mRNA metabolism. FMRP has been largely studied in the brain, where the absence of this protein leads to fragile X syndrome, the most frequent form of inherited intellectual disability. Since the identification of the FMRP gene in 1991, many studies have primarily focused on understanding the function/s of this protein. Hundreds of potential FMRP mRNA targets and several interacting proteins have been identified. Here, we report the identification of FMRP mRNA targets in the mammalian brain that support the key role of this protein during brain development and in regulating synaptic plasticity. We compared the genes from databases and genome-wide association studies with the brain FMRP transcriptome, and identified several FMRP mRNA targets associated with autism spectrum disorders, mood disorders and schizophrenia, showing a potential common pathway/s for these apparently different disorders. PMID:24167470

Similar brain activation during false belief tasks in a large sample of adults with and without autism.

PubMed

Dufour, Nicholas; Redcay, Elizabeth; Young, Liane; Mavros, Penelope L; Moran, Joseph M; Triantafyllou, Christina; Gabrieli, John D E; Saxe, Rebecca

2013-01-01

Reading about another person's beliefs engages 'Theory of Mind' processes and elicits highly reliable brain activation across individuals and experimental paradigms. Using functional magnetic resonance imaging, we examined activation during a story task designed to elicit Theory of Mind processing in a very large sample of neurotypical (N = 462) individuals, and a group of high-functioning individuals with autism spectrum disorders (N = 31), using both region-of-interest and whole-brain analyses. This large sample allowed us to investigate group differences in brain activation to Theory of Mind tasks with unusually high sensitivity. There were no differences between neurotypical participants and those diagnosed with autism spectrum disorder. These results imply that the social cognitive impairments typical of autism spectrum disorder can occur without measurable changes in the size, location or response magnitude of activity during explicit Theory of Mind tasks administered to adults.

The Effect of Combat Traumatic Brain Injury on Executive Function

DTIC Science & Technology

2011-03-01

attention deficit / hyperactivity disorder ( ADHD ) as these are similar to problems of executive functioning...affect working memory. Also the neurotransmitters active in attention deficit / hyperactivity disorder ( ADHD ), which displays symptoms similar to those of... disorders such as autism and attention - deficit / hyperactivity disorder (Zelazo, P.D., 2005). As children grow they learn to chose and select,

Classifying social anxiety disorder using multivoxel pattern analyses of brain function and structure☆

PubMed Central

Frick, Andreas; Gingnell, Malin; Marquand, Andre F.; Howner, Katarina; Fischer, Håkan; Kristiansson, Marianne; Williams, Steven C.R.; Fredrikson, Mats; Furmark, Tomas

2014-01-01

Functional neuroimaging of social anxiety disorder (SAD) support altered neural activation to threat-provoking stimuli focally in the fear network, while structural differences are distributed over the temporal and frontal cortices as well as limbic structures. Previous neuroimaging studies have investigated the brain at the voxel level using mass-univariate methods which do not enable detection of more complex patterns of activity and structural alterations that may separate SAD from healthy individuals. Support vector machine (SVM) is a supervised machine learning method that capitalizes on brain activation and structural patterns to classify individuals. The aim of this study was to investigate if it is possible to discriminate SAD patients (n = 14) from healthy controls (n = 12) using SVM based on (1) functional magnetic resonance imaging during fearful face processing and (2) regional gray matter volume. Whole brain and region of interest (fear network) SVM analyses were performed for both modalities. For functional scans, significant classifications were obtained both at whole brain level and when restricting the analysis to the fear network while gray matter SVM analyses correctly classified participants only when using the whole brain search volume. These results support that SAD is characterized by aberrant neural activation to affective stimuli in the fear network, while disorder-related alterations in regional gray matter volume are more diffusely distributed over the whole brain. SVM may thus be useful for identifying imaging biomarkers of SAD. PMID:24239689

Adaptations for Students with ADHD

ERIC Educational Resources Information Center

McGrady, Mart

2005-01-01

ADHD is a neurobiological-based brain disorder, most often hereditary, affecting nearly one in twenty students. The ADHD brain functions differently because the area between the frontal lobe and rear lobe is having short-circuit problems and is not transmitting necessary information. The technical part of the disorder does not engage us as…

The diagnosis of organic brain syndrome.

PubMed

Berger, D M

1977-03-01

Because it stems from a variety of causes and interacting factors, organic brain syndrome is a difficult condition to diagnose. Several factors make it distinguishable from functional disorders, schizophrenia or hysteria. The syndrome cannot be considered in isolation from the patient's personality, however, since this will affect his coping with the disorder.

Potential Beneficial Effects of Probiotics on Human Migraine Headache: A Literature Review.

PubMed

Dai, Yu-Jie; Wang, Hai-Yan; Wang, Xi-Jian; Kaye, Alan D; Sun, Yong-Hai

2017-02-01

Recent studies have shown that migraine headache is often associated with concomitant gastrointestinal diseases. There is a higher prevalence of headaches in patients with gastrointestinal disorders. These associations between migraine and gastrointestinal disorders suggest a potential link to a bidirectional modulation of gut microbiota and brain function. The underlying working mechanistic links between migraine and gastrointestinal diseases may include increased intestinal epithelial permeability and inflammation. This review presents an overview of the relationship between gut microbiota and brain function, especially with regard to migraine headache. Literature review. Anesthesia and Operation Center, Department of Anesthesiology, Chinese PLA General Hospital. The present investigation included a PubMed search using the following terms: migraine headache, gut microbiota, brain function, and probiotics. In this literature review, we mainly discussed the relationship between gut microbiota and brain function, especially with regard to migraine headache. The potential effects of probiotics supplement on migraine headache were also included. There is limited evidence from clinical studies of the positive effects of probiotics in patients with migraine headache. Large-scale randomized, placebo-controlled clinical trials are warranted to evaluate the clinical efficacy and safety of probiotics in patients with migraine headache. Similar to migraine headache, disorders of the brain involving depression and anxiety have been demonstrated to be associated with increased gut permeability. An improvement in gut microbiota and reduction of inflammation can have positive effects on strengthening gut and brain function. Moreover, it can be inferred that probiotics may have a beneficial effect on the frequency and severity of migraine headache attacks. Large-scale randomized, placebo-controlled studies are warranted in the future to evaluate the clinical efficacy and safety of probiotics in patients with migraine headache.Key words: Migraine headache, gut microbiota, brain function, probiotics.

Meta-connectomics: human brain network and connectivity meta-analyses.

PubMed

Crossley, N A; Fox, P T; Bullmore, E T

2016-04-01

Abnormal brain connectivity or network dysfunction has been suggested as a paradigm to understand several psychiatric disorders. We here review the use of novel meta-analytic approaches in neuroscience that go beyond a summary description of existing results by applying network analysis methods to previously published studies and/or publicly accessible databases. We define this strategy of combining connectivity with other brain characteristics as 'meta-connectomics'. For example, we show how network analysis of task-based neuroimaging studies has been used to infer functional co-activation from primary data on regional activations. This approach has been able to relate cognition to functional network topology, demonstrating that the brain is composed of cognitively specialized functional subnetworks or modules, linked by a rich club of cognitively generalized regions that mediate many inter-modular connections. Another major application of meta-connectomics has been efforts to link meta-analytic maps of disorder-related abnormalities or MRI 'lesions' to the complex topology of the normative connectome. This work has highlighted the general importance of network hubs as hotspots for concentration of cortical grey-matter deficits in schizophrenia, Alzheimer's disease and other disorders. Finally, we show how by incorporating cellular and transcriptional data on individual nodes with network models of the connectome, studies have begun to elucidate the microscopic mechanisms underpinning the macroscopic organization of whole-brain networks. We argue that meta-connectomics is an exciting field, providing robust and integrative insights into brain organization that will likely play an important future role in consolidating network models of psychiatric disorders.

Exploring difference and overlap between schizophrenia, schizoaffective and bipolar disorders using resting-state brain functional networks.

PubMed

Du, Yuhui; Liu, Jingyu; Sui, Jing; He, Hao; Pearlson, Godfrey D; Calhoun, Vince D

2014-01-01

Schizophrenia, schizoaffective and bipolar disorders share some common symptoms. However, the biomarkers underlying those disorders remain unclear. In fact, there is still controversy about the schizoaffective disorder with respect to its validity of independent category and its relationship with schizophrenia and bipolar disorders. In this paper, based on brain functional networks extracted from resting-state fMRI using a recently proposed group information guided ICA (GIG-ICA) method, we explore the biomarkers for discriminating healthy controls, schizophrenia patients, bipolar patients, and patients with two symptom defined subsets of schizoaffective disorder, and then investigate the relationship between different groups. The results demonstrate that the discriminating regions mainly including frontal, parietal, precuneus, cingulate, supplementary motor, cerebellar, insular and supramarginal cortices perform well in distinguishing the different diagnostic groups. The results also suggest that schizoaffective disorder may be an independent disorder, although its subtype characterized by depressive episodes shares more similarity with schizophrenia.

Disrupted Cerebro-cerebellar Intrinsic Functional Connectivity in Young Adults with High-functioning Autism Spectrum Disorder: A Data-driven, Whole-brain, High Temporal Resolution fMRI Study.

PubMed

Arnold Anteraper, Sheeba; Guell, Xavier; D'Mello, Anila; Joshi, Neha; Whitfield-Gabrieli, Susan; Joshi, Gagan

2018-06-13

To examine the resting-state functional-connectivity (RsFc) in young adults with high-functioning autism spectrum disorder (HF-ASD) using state-of-the-art fMRI data acquisition and analysis techniques. Simultaneous multi-slice, high temporal resolution fMRI acquisition; unbiased whole-brain connectome-wide multivariate pattern analysis (MVPA) techniques for assessing RsFc; and post-hoc whole-brain seed-to-voxel analyses using MVPA results as seeds. MVPA revealed two clusters of abnormal connectivity in the cerebellum. Whole-brain seed-based functional connectivity analyses informed by MVPA-derived clusters showed significant under connectivity between the cerebellum and social, emotional, and language brain regions in the HF-ASD group compared to healthy controls. The results we report are coherent with existing structural, functional, and RsFc literature in autism, extend previous literature reporting cerebellar abnormalities in the neuropathology of autism, and highlight the cerebellum as a potential target for therapeutic, diagnostic, predictive, and prognostic developments in ASD. The description of functional connectivity abnormalities using whole-brain, data-driven analyses as reported in the present study may crucially advance the development of ASD biomarkers, targets for therapeutic interventions, and neural predictors for measuring treatment response.

Congenital Amusia Persists in the Developing Brain after Daily Music Listening

PubMed Central

Mignault Goulet, Geneviève; Moreau, Patricia; Robitaille, Nicolas; Peretz, Isabelle

2012-01-01

Congenital amusia is a neurodevelopmental disorder that affects about 3% of the adult population. Adults experiencing this musical disorder in the absence of macroscopically visible brain injury are described as cases of congenital amusia under the assumption that the musical deficits have been present from birth. Here, we show that this disorder can be expressed in the developing brain. We found that (10–13 year-old) children exhibit a marked deficit in the detection of fine-grained pitch differences in both musical and acoustical context in comparison to their normally developing peers comparable in age and general intelligence. This behavioral deficit could be traced down to their abnormal P300 brain responses to the detection of subtle pitch changes. The altered pattern of electrical activity does not seem to arise from an anomalous functioning of the auditory cortex, because all early components of the brain potentials, the N100, the MMN, and the P200 appear normal. Rather, the brain and behavioral measures point to disrupted information propagation from the auditory cortex to other cortical regions. Furthermore, the behavioral and neural manifestations of the disorder remained unchanged after 4 weeks of daily musical listening. These results show that congenital amusia can be detected in childhood despite regular musical exposure and normal intellectual functioning. PMID:22606299

In vivo functional connectome of human brainstem nuclei of the ascending arousal, autonomic, and motor systems by high spatial resolution 7-Tesla fMRI.

PubMed

Bianciardi, Marta; Toschi, Nicola; Eichner, Cornelius; Polimeni, Jonathan R; Setsompop, Kawin; Brown, Emery N; Hämäläinen, Matti S; Rosen, Bruce R; Wald, Lawrence L

2016-06-01

Our aim was to map the in vivo human functional connectivity of several brainstem nuclei with the rest of the brain by using seed-based correlation of ultra-high magnetic field functional magnetic resonance imaging (fMRI) data. We used the recently developed template of 11 brainstem nuclei derived from multi-contrast structural MRI at 7 Tesla as seed regions to determine their connectivity to the rest of the brain. To achieve this, we used the increased contrast-to-noise ratio of 7-Tesla fMRI compared with 3 Tesla and time-efficient simultaneous multi-slice imaging to cover the brain with high spatial resolution (1.1-mm isotropic nominal resolution) while maintaining a short repetition time (2.5 s). The delineated Pearson's correlation-based functional connectivity diagrams (connectomes) of 11 brainstem nuclei of the ascending arousal, motor, and autonomic systems from 12 controls are presented and discussed in the context of existing histology and animal work. Considering that the investigated brainstem nuclei play a crucial role in several vital functions, the delineated preliminary connectomes might prove useful for future in vivo research and clinical studies of human brainstem function and pathology, including disorders of consciousness, sleep disorders, autonomic disorders, Parkinson's disease, and other motor disorders.

Deep brain stimulation for psychiatric disorders: Is there an impact on social functioning?

PubMed Central

Saleh, Christian; Hasler, Gregor

2017-01-01

Background: Deep brain stimulation (DBS) for refractory psychiatric disorders shows promising effects on symptom-reduction, however, little is known regarding the effects of DBS on social outcome. Methods: A PubMed search based on original studies of DBS for psychiatric disorders [treatment resistant depression (TRD), Gilles de la Tourette's syndrome (GTS), and obsessive compulsive disorder (OCD)] was conducted. Data on social outcome following surgery were extracted and analyzed. Results: Social functioning was not a primary outcome measure in the reviewed article. The literature is incomplete and inconclusive on this variable, however from the reported data, there is some evidence that DBS has the potential to improve social functioning. Conclusions: More systematic and detailed data gathering and reporting on social outcome with longer follow-ups are needed to evaluate more exhaustively the role of DBS in refractory psychiatric disorders. PMID:28781911

Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder.

PubMed

Palmen, Saskia J M C; Hulshoff Pol, Hilleke E; Kemner, Chantal; Schnack, Hugo G; Durston, Sarah; Lahuis, Bertine E; Kahn, René S; Van Engeland, Herman

2005-04-01

To establish whether high-functioning children with autism spectrum disorder (ASD) have enlarged brains in later childhood, and if so, whether this enlargement is confined to the gray and/or to the white matter and whether it is global or more prominent in specific brain regions. Brain MRI scans were acquired from 21 medication-naive, high-functioning children with ASD between 7 and 15 years of age and 21 comparison subjects matched for gender, age, IQ, height, weight, handedness, and parental education, but not pubertal status. Patients showed a significant increase of 6% in intracranium, total brain, cerebral gray matter, cerebellum, and of more than 40% in lateral and third ventricles compared to controls. The cortical gray-matter volume was evenly affected in all lobes. After correction for brain volume, ventricular volumes remained significantly larger in patients. High-functioning children with ASD showed a global increase in gray-matter, but not white-matter and cerebellar volume, proportional to the increase in brain volume, and a disproportional increase in ventricular volumes, still present after correction for brain volume. Advanced pubertal development in the patients compared to the age-matched controls may have contributed to the findings reported in the present study.

The Human BNST: Functional Role in Anxiety and Addiction

PubMed Central

Avery, S N; Clauss, J A; Blackford, J U

2016-01-01

The consequences of chronic stress on brain structure and function are far reaching. Whereas stress can produce short-term adaptive changes in the brain, chronic stress leads to long-term maladaptive changes that increase vulnerability to psychiatric disorders, such as anxiety and addiction. These two disorders are the most prevalent psychiatric disorders in the United States, and are typically chronic, disabling, and highly comorbid. Emerging evidence implicates a tiny brain region—the bed nucleus of the stria terminalis (BNST)—in the body's stress response and in anxiety and addiction. Rodent studies provide compelling evidence that the BNST plays a central role in sustained threat monitoring, a form of adaptive anxiety, and in the withdrawal and relapse stages of addiction; however, little is known about the role of BNST in humans. Here, we review current evidence for BNST function in humans, including evidence for a role in the production of both adaptive and maladaptive anxiety. We also review preliminary evidence of the role of BNST in addiction in humans. Together, these studies provide a foundation of knowledge about the role of BNST in adaptive anxiety and stress-related disorders. Although the field is in its infancy, future investigations of human BNST function have tremendous potential to illuminate mechanisms underlying stress-related disorders and identify novel neural targets for treatment. PMID:26105138

The Human BNST: Functional Role in Anxiety and Addiction.

PubMed

Avery, S N; Clauss, J A; Blackford, J U

2016-01-01

The consequences of chronic stress on brain structure and function are far reaching. Whereas stress can produce short-term adaptive changes in the brain, chronic stress leads to long-term maladaptive changes that increase vulnerability to psychiatric disorders, such as anxiety and addiction. These two disorders are the most prevalent psychiatric disorders in the United States, and are typically chronic, disabling, and highly comorbid. Emerging evidence implicates a tiny brain region-the bed nucleus of the stria terminalis (BNST)-in the body's stress response and in anxiety and addiction. Rodent studies provide compelling evidence that the BNST plays a central role in sustained threat monitoring, a form of adaptive anxiety, and in the withdrawal and relapse stages of addiction; however, little is known about the role of BNST in humans. Here, we review current evidence for BNST function in humans, including evidence for a role in the production of both adaptive and maladaptive anxiety. We also review preliminary evidence of the role of BNST in addiction in humans. Together, these studies provide a foundation of knowledge about the role of BNST in adaptive anxiety and stress-related disorders. Although the field is in its infancy, future investigations of human BNST function have tremendous potential to illuminate mechanisms underlying stress-related disorders and identify novel neural targets for treatment.

The neurology of mTOR.

PubMed

Lipton, Jonathan O; Sahin, Mustafa

2014-10-22

The mechanistic target of rapamycin (mTOR) signaling pathway is a crucial cellular signaling hub that, like the nervous system itself, integrates internal and external cues to elicit critical outputs including growth control, protein synthesis, gene expression, and metabolic balance. The importance of mTOR signaling to brain function is underscored by the myriad disorders in which mTOR pathway dysfunction is implicated, such as autism, epilepsy, and neurodegenerative disorders. Pharmacological manipulation of mTOR signaling holds therapeutic promise and has entered clinical trials for several disorders. Here, we review the functions of mTOR signaling in the normal and pathological brain, highlighting ongoing efforts to translate our understanding of cellular physiology into direct medical benefit for neurological disorders.

Sparse network-based models for patient classification using fMRI

PubMed Central

Rosa, Maria J.; Portugal, Liana; Hahn, Tim; Fallgatter, Andreas J.; Garrido, Marta I.; Shawe-Taylor, John; Mourao-Miranda, Janaina

2015-01-01

Pattern recognition applied to whole-brain neuroimaging data, such as functional Magnetic Resonance Imaging (fMRI), has proved successful at discriminating psychiatric patients from healthy participants. However, predictive patterns obtained from whole-brain voxel-based features are difficult to interpret in terms of the underlying neurobiology. Many psychiatric disorders, such as depression and schizophrenia, are thought to be brain connectivity disorders. Therefore, pattern recognition based on network models might provide deeper insights and potentially more powerful predictions than whole-brain voxel-based approaches. Here, we build a novel sparse network-based discriminative modeling framework, based on Gaussian graphical models and L1-norm regularized linear Support Vector Machines (SVM). In addition, the proposed framework is optimized in terms of both predictive power and reproducibility/stability of the patterns. Our approach aims to provide better pattern interpretation than voxel-based whole-brain approaches by yielding stable brain connectivity patterns that underlie discriminative changes in brain function between the groups. We illustrate our technique by classifying patients with major depressive disorder (MDD) and healthy participants, in two (event- and block-related) fMRI datasets acquired while participants performed a gender discrimination and emotional task, respectively, during the visualization of emotional valent faces. PMID:25463459

Right brain, left brain in depressive disorders: Clinical and theoretical implications of behavioral, electrophysiological and neuroimaging findings.

PubMed

Bruder, Gerard E; Stewart, Jonathan W; McGrath, Patrick J

2017-07-01

The right and left side of the brain are asymmetric in anatomy and function. We review electrophysiological (EEG and event-related potential), behavioral (dichotic and visual perceptual asymmetry), and neuroimaging (PET, MRI, NIRS) evidence of right-left asymmetry in depressive disorders. Recent electrophysiological and fMRI studies of emotional processing have provided new evidence of altered laterality in depressive disorders. EEG alpha asymmetry and neuroimaging findings at rest and during cognitive or emotional tasks are consistent with reduced left prefrontal activity in depressed patients, which may impair downregulation of amygdala response to negative emotional information. Dichotic listening and visual hemifield findings for non-verbal or emotional processing have revealed abnormal perceptual asymmetry in depressive disorders, and electrophysiological findings have shown reduced right-lateralized responsivity to emotional stimuli in occipitotemporal or parietotemporal cortex. We discuss models of neural networks underlying these alterations. Of clinical relevance, individual differences among depressed patients on measures of right-left brain function are related to diagnostic subtype of depression, comorbidity with anxiety disorders, and clinical response to antidepressants or cognitive behavioral therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bipolar disorder: a neural network perspective on a disorder of emotion and motivation.

PubMed

Wessa, Michèle; Kanske, Philipp; Linke, Julia

2014-01-01

Bipolar disorder (BD) is a severe, chronic disease with a heritability of 60-80%. BD is frequently misdiagnosed due to phenomenological overlap with other psychopathologies, an important issue that calls for the identification of biological and psychological vulnerability and disease markers. Altered structural and functional connectivity, mainly between limbic and prefrontal brain areas, have been proposed to underlie emotional and motivational dysregulation in BD and might represent relevant vulnerability and disease markers. In the present laboratory review we discuss functional and structural neuroimaging findings on emotional and motivational dysregulation from our research group in BD patients and healthy individuals at risk to develop BD. As a main result of our studies, we observed altered orbitofrontal and limbic activity and reduced connectivity between dorsal prefrontal and limbic brain regions, as well as reduced integrity of fiber tracts connecting prefrontal and subcortical brain structures in BD patients and high-risk individuals. Our results provide novel insights into pathophysiological mechanisms of bipolar disorder. The current laboratory review provides a specific view of our group on altered brain connectivity and underlying psychological processes in bipolar disorder based on our own work, integrating relevant findings from others. Thereby we attempt to advance neuropsychobiological models of BD.

Structural and functional connectivity of the human brain in autism spectrum disorders and attention-deficit/hyperactivity disorder: A rich club organization study

PubMed Central

Ray, Siddharth; Miller, Meghan; Karalunas, Sarah; Robertson, C.J.; Grayson, David; Cary, Paul; Hawkey, Elizabeth; Painter, Julia G.; Kriz, Daniel; Fombonne, Eric; Nigg, Joel T.; Fair, Damien A.

2015-01-01

Attention deficit hyperactive disorder (ADHD) and Autism spectrum disorders (ASD) are two of the most common and vexing neurodevelopmental disorders among children. Although the two disorders share many behavioral and neuropsychological characteristics, most MRI studies examine only one of the disorders at a time. Using graph theory combined with structural and functional connectivity, we examined the large-scale network organization among three groups of children: a group with ADHD (8-12 years, n = 20), a group with ASD (7-13 years, n = 16), and typically developing controls (TD) (8-12 years, n = 20). We apply the concept of the rich-club organization, whereby central, highly connected hub regions are also highly connected to themselves. We examine the brain into two different network domains: (1) inside a rich-club network phenomena, and (2) outside a rich-club network phenomena. ASD and ADHD populations had markedly different patterns of rich club and non rich-club connections in both functional and structural data. The ASD group exhibited higher connectivity in structural and functional networks but only inside the rich-club networks. These findings were replicated using the autism brain imaging data exchange (ABIDE) dataset with ASD (n = 85) and TD (n = 101). The ADHD group exhibited a lower generalized fractional anisotropy (GFA) and functional connectivity inside the rich-club networks, but a higher number of axonal fibers and correlation coefficient values outside the rich-club. Despite some shared biological features and frequent comorbity, these data suggest ADHD and ASD exhibit distinct large-scale connectivity patterns in middle childhood. PMID:25116862

The contribution of single case studies to the neuroscience of vision.

PubMed

Zihl, Josef; Heywood, Charles A

2016-03-01

Visual neuroscience is concerned with the neurobiological foundations of visual perception, that is, the morphological, physiological, and functional organization of the visual brain and its co-operative partners. One important approach for understanding the functional organization of the visual brain is the study of visual perception from the pathological perspective. The study of patients with focal injury to the visual brain allows conclusions about the representation of visual perceptual functions in the framework of association and dissociation of functions. Selective disorders have been reported for more "elementary" visual capabilities, for example, color and movement vision, but also for visuo-cognitive capacities, such as visual agnosia or the visual field of attention. Because these visual disorders occur rather seldom as selective and specific dysfunctions, single cases have always played, and still play, a significant role in gaining insights into the functional organization of the visual brain. © 2016 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

NIRS Study of the Effects of Computerized Brain Training Games for Cognitive Rehabilitation of Major Depressive Disorder Patients in Remission: A Pilot Study.

PubMed

Payzieva, Shaira; Maxmudova, D

2014-01-01

We used functional Near-Infrared Spectroscopy (fNIRS) to estimate brain activity in Major Depressive Disorder (MDD) patients (in remission), while they played a computerized brain training games for cognitive rehabilitation. MDD is characterized by marked deterioration in affect as well as significant impairment in cognitive function. It was found, that depressed patients showed long-lasting impaired cognitive performance on cognitive demanding tasks despite significant improvement in the depression symptoms. Previous studies have shown that video games can improve cognitive functions. But assessment was made only with cognitive tests. The main objective of this research was to study the effects of brain training games on cognitive functions of MDD patients in remission with objective instrumental NIRS method. Tissue oxygen saturation (StO2) and absolute concentrations of oxyhemoglobin ([O2Hb]), deoxyhemoglobin ([HHb]) and total hemoglobin ([tHb]) were measured by functional near-infrared spectroscopy (fNIRS) - Oxyprem (BORL, Zurich, Switzerland). Preliminary results are discussed.

Developmental origins of brain disorders: roles for dopamine

PubMed Central

Money, Kelli M.; Stanwood, Gregg D.

2013-01-01

Neurotransmitters and neuromodulators, such as dopamine, participate in a wide range of behavioral and cognitive functions in the adult brain, including movement, cognition, and reward. Dopamine-mediated signaling plays a fundamental neurodevelopmental role in forebrain differentiation and circuit formation. These developmental effects, such as modulation of neuronal migration and dendritic growth, occur before synaptogenesis and demonstrate novel roles for dopaminergic signaling beyond neuromodulation at the synapse. Pharmacologic and genetic disruptions demonstrate that these effects are brain region- and receptor subtype-specific. For example, the striatum and frontal cortex exhibit abnormal neuronal structure and function following prenatal disruption of dopamine receptor signaling. Alterations in these processes are implicated in the pathophysiology of neuropsychiatric disorders, and emerging studies of neurodevelopmental disruptions may shed light on the pathophysiology of abnormal neuronal circuitry in neuropsychiatric disorders. PMID:24391541

Epigenetics in Developmental Disorder: ADHD and Endophenotypes

PubMed Central

Archer, Trevor; Oscar-Berman, Marlene; Blum, Kenneth

2011-01-01

Heterogeneity in attention-deficit/hyperactivity disorder (ADHD), with complex interactive operations of genetic and environmental factors, is expressed in a variety of disorder manifestations: severity, co-morbidities of symptoms, and the effects of genes on phenotypes. Neurodevelopmental influences of genomic imprinting have set the stage for the structural-physiological variations that modulate the cognitive, affective, and pathophysiological domains of ADHD. The relative contributions of genetic and environmental factors provide rapidly proliferating insights into the developmental trajectory of the condition, both structurally and functionally. Parent-of-origin effects seem to support the notion that genetic risks for disease process debut often interact with the social environment, i.e., the parental environment in infants and young children. The notion of endophenotypes, markers of an underlying liability to the disorder, may facilitate detection of genetic risks relative to a complex clinical disorder. Simple genetic association has proven insufficient to explain the spectrum of ADHD. At a primary level of analysis, the consideration of epigenetic regulation of brain signalling mechanisms, dopamine, serotonin, and noradrenaline is examined. Neurotrophic factors that participate in the neurogenesis, survival, and functional maintenance of brain systems, are involved in neuroplasticity alterations underlying brain disorders, and are implicated in the genetic predisposition to ADHD, but not obviously, nor in a simple or straightforward fashion. In the context of intervention, genetic linkage studies of ADHD pharmacological intervention have demonstrated that associations have fitted the “drug response phenotype,” rather than the disorder diagnosis. Despite conflicting evidence for the existence, or not, of genetic associations between disorder diagnosis and genes regulating the structure and function of neurotransmitters and brain-derived neurotrophic factor (BDNF), associations between symptoms-profiles endophenotypes and single nucleotide polymorphisms appear reassuring. PMID:22224195

The Diagnosis of Organic Brain Syndrome

PubMed Central

Berger, David M.

1977-01-01

Because it stems from a variety of causes and interacting factors, organic brain syndrome is a difficult condition to diagnose. Several factors make it distinguishable from functional disorders, schizophrenia or hysteria. The syndrome cannot be considered in isolation from the patient's personality, however, since this will affect his coping with the disorder. PMID:21304779

Bipolar disorder type I and II show distinct relationships between cortical thickness and executive function.

PubMed

Abé, C; Rolstad, S; Petrovic, P; Ekman, C-J; Sparding, T; Ingvar, M; Landén, M

2018-06-15

Frontal cortical abnormalities and executive function impairment co-occur in bipolar disorder. Recent studies have shown that bipolar subtypes differ in the degree of structural and functional impairments. The relationships between cognitive performance and cortical integrity have not been clarified and might differ across patients with bipolar disorder type I, II, and healthy subjects. Using a vertex-wise whole-brain analysis, we investigated how cortical integrity, as measured by cortical thickness, correlates with executive performance in patients with bipolar disorder type I, II, and controls (N = 160). We found focal associations between executive function and cortical thickness in the medial prefrontal cortex in bipolar II patients and controls, but not in bipolar I disorder. In bipolar II patients, we observed additional correlations in lateral prefrontal and occipital regions. Our findings suggest that bipolar disorder patients show altered structure-function relationships, and importantly that those relationships may differ between bipolar subtypes. The findings are line with studies suggesting subtype-specific neurobiological and cognitive profiles. This study contributes to a better understanding of brain structure-function relationships in bipolar disorder and gives important insights into the neuropathophysiology of diagnostic subtypes. © 2018 The Authors Acta Psychiatrica Scandinavica Published by John Wiley & Sons Ltd.

Uncovering the mechanism(s) of deep brain stimulation

NASA Astrophysics Data System (ADS)

Gang, Li; Chao, Yu; Ling, Lin; C-Y Lu, Stephen

2005-01-01

Deep brain stimulators, often called `pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

Abnormal small-world architecture of top–down control networks in obsessive–compulsive disorder

PubMed Central

Zhang, Tijiang; Wang, Jinhui; Yang, Yanchun; Wu, Qizhu; Li, Bin; Chen, Long; Yue, Qiang; Tang, Hehan; Yan, Chaogan; Lui, Su; Huang, Xiaoqi; Chan, Raymond C.K.; Zang, Yufeng; He, Yong; Gong, Qiyong

2011-01-01

Background Obsessive–compulsive disorder (OCD) is a common neuropsychiatric disorder that is characterized by recurrent intrusive thoughts, ideas or images and repetitive ritualistic behaviours. Although focal structural and functional abnormalities in specific brain regions have been widely studied in populations with OCD, changes in the functional relations among them remain poorly understood. This study examined OCD–related alterations in functional connectivity patterns in the brain’s top–down control network. Methods We applied resting-state functional magnetic resonance imaging to investigate the correlation patterns of intrinsic or spontaneous blood oxygen level–dependent signal fluctuations in 18 patients with OCD and 16 healthy controls. The brain control networks were first constructed by thresholding temporal correlation matrices of 39 brain regions associated with top–down control and then analyzed using graph theory-based approaches. Results Compared with healthy controls, the patients with OCD showed decreased functional connectivity in the posterior temporal regions and increased connectivity in various control regions such as the cingulate, precuneus, thalamus and cerebellum. Furthermore, the brain’s control networks in the healthy controls showed small-world architecture (high clustering coefficients and short path lengths), suggesting an optimal balance between modularized and distributed information processing. In contrast, the patients with OCD showed significantly higher local clustering, implying abnormal functional organization in the control network. Further analysis revealed that the changes in network properties occurred in regions of increased functional connectivity strength in patients with OCD. Limitations The patient group in the present study was heterogeneous in terms of symptom clusters, and most of the patients with OCD were medicated. Conclusion Our preliminary results suggest that the organizational patterns of intrinsic brain activity in the control networks are altered in patients with OCD and thus provide empirical evidence for aberrant functional connectivity in the large-scale brain systems in people with this disorder. PMID:20964957

A Genome-Wide Association Study of Amygdala Activation in Youths with and without Bipolar Disorder

ERIC Educational Resources Information Center

Liu, Xinmin; Akula, Nirmala; Skup, Martha; Brotman, Melissa A.; Leibenluft, Ellen; McMahon, Francis J.

2010-01-01

Objective: Functional magnetic resonance imaging is commonly used to characterize brain activity underlying a variety of psychiatric disorders. A previous functional magnetic resonance imaging study found that amygdala activation during a face-processing task differed between pediatric patients with bipolar disorder (BD) and healthy controls. We…

Research Review: Environmental exposures, neurodevelopment and child mental health – new paradigms for the study of brain and behavioral effects

PubMed Central

Rauh, Virginia A.; Margolis, Amy

2016-01-01

Background Environmental exposures play a critical role in the genesis of some child mental health problems. Methods We open with a discussion of children’s vulnerability to neurotoxic substances, changes in the distribution of toxic exposures, and co-occurrence of social and physical exposures. We address trends in prevalence of mental health disorders, and approaches to the definition of disorders that are sensitive to the subtle effects of toxic exposures. We suggest broadening outcomes to include dimensional measures of autism spectrum disorders, attention deficit hyperactivity disorder, and child learning capacity, as well as direct assessment of brain function. Findings We consider the impact of two important exposures on children’s mental health: lead and pesticides. We argue that longitudinal research designs may capture the cascading effects of exposures across biological systems and the full-range of neuropsychological endpoints. Neuroimaging is a valuable tool for observing brain maturation under varying environmental conditions. A dimensional approach to measurement may be sensitive to subtle sub-clinical toxic effects, permitting the development of exposure-related profiles and testing of complex functional relationships between brain and behavior. Questions about the neurotoxic effects of chemicals become more pressing when viewed through the lens of environmental justice. Conclusions Reduction in the burden of child mental health disorders will require longitudinal study of neurotoxic exposures, incorporating dimensional approaches to outcome assessment and measures of brain function. Research that seeks to identify links between toxic exposures and mental health outcomes has enormous public health and societal value. PMID:26987761

Research Review: Environmental exposures, neurodevelopment, and child mental health - new paradigms for the study of brain and behavioral effects.

PubMed

Rauh, Virginia A; Margolis, Amy E

2016-07-01

Environmental exposures play a critical role in the genesis of some child mental health problems. We open with a discussion of children's vulnerability to neurotoxic substances, changes in the distribution of toxic exposures, and cooccurrence of social and physical exposures. We address trends in prevalence of mental health disorders, and approaches to the definition of disorders that are sensitive to the subtle effects of toxic exposures. We suggest broadening outcomes to include dimensional measures of autism spectrum disorders, attention-deficit hyperactivity disorder, and child learning capacity, as well as direct assessment of brain function. We consider the impact of two important exposures on children's mental health: lead and pesticides. We argue that longitudinal research designs may capture the cascading effects of exposures across biological systems and the full-range of neuropsychological endpoints. Neuroimaging is a valuable tool for observing brain maturation under varying environmental conditions. A dimensional approach to measurement may be sensitive to subtle subclinical toxic effects, permitting the development of exposure-related profiles and testing of complex functional relationships between brain and behavior. Questions about the neurotoxic effects of chemicals become more pressing when viewed through the lens of environmental justice. Reduction in the burden of child mental health disorders will require longitudinal study of neurotoxic exposures, incorporating dimensional approaches to outcome assessment, and measures of brain function. Research that seeks to identify links between toxic exposures and mental health outcomes has enormous public health and societal value. © 2016 Association for Child and Adolescent Mental Health.

Differential brain network activity across mood states in bipolar disorder.

PubMed

Brady, Roscoe O; Tandon, Neeraj; Masters, Grace A; Margolis, Allison; Cohen, Bruce M; Keshavan, Matcheri; Öngür, Dost

2017-01-01

This study aimed to identify how the activity of large-scale brain networks differs between mood states in bipolar disorder. The authors measured spontaneous brain activity in subjects with bipolar disorder in mania and euthymia and compared these states to a healthy comparison population. 23 subjects with bipolar disorder type I in a manic episode, 24 euthymic bipolar I subjects, and 23 matched healthy comparison (HC) subjects underwent resting state fMRI scans. Using an existing parcellation of the whole brain, we measured functional connectivity between brain regions and identified significant differences between groups. In unbiased whole-brain analyses, functional connectivity between parietal, occipital, and frontal nodes within the dorsal attention network (DAN) were significantly greater in mania than euthymia or HC subjects. In the default mode network (DMN), connectivity between dorsal frontal nodes and the rest of the DMN differentiated both mood state and diagnosis. The bipolar groups were separate cohorts rather than subjects imaged longitudinally across mood states. Bipolar mood states are associated with highly significant alterations in connectivity in two large-scale brain networks. These same networks also differentiate bipolar mania and euthymia from a HC population. State related changes in DAN and DMN connectivity suggest a circuit based pathology underlying cognitive dysfunction as well as activity/reactivity in bipolar mania. Altered activities in neural networks may be biomarkers of bipolar disorder diagnosis and mood state that are accessible to neuromodulation and are promising novel targets for scientific investigation and possible clinical intervention. Copyright © 2016 Elsevier B.V. All rights reserved.

A role for the serotonin reuptake transporter in the brain and intestinal features of autism spectrum disorders and developmental antidepressant exposure.

PubMed

Margolis, Kara Gross

2017-10-01

Many disease conditions considered CNS-predominant harbor significant intestinal comorbidities. Serotonin (5-HT) and the serotonin reuptake transporter (SERT) have increasingly been shown to play important roles in both brain and intestinal development and long-term function. 5-HT and SERT may thus modulate critical functions in the development and perpetuation of brain-gut axis disease. We discuss the potential roles of 5-HT and SERT in the brain and intestinal manifestations of autism spectrum disorders and developmental antidepressant exposure. The potential therapeutic value of 5-HT 4 modulation in the subsequent treatment of these conditions is also addressed. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered intrinsic functional brain architecture in female patients with bulimia nervosa

PubMed Central

Wang, Li; Kong, Qing-Mei; Li, Ke; Li, Xue-Ni; Zeng, Ya-Wei; Chen, Chao; Qian, Ying; Feng, Shi-Jie; Li, Ji-Tao; Su, Yun’Ai; Correll, Christoph U.; Mitchell, Philip B.; Yan, Chao-Gan; Zhang, Da-Rong; Si, Tian-Mei

2017-01-01

Background Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. Methods We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. Results We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. Limitations We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. Conclusion Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large-scale distributed brain regions. These abnormalities contribute to more comprehensive understanding of the neural mechanism underlying pathological eating and body perception in women with bulimia nervosa. PMID:28949286

Altered intrinsic functional brain architecture in female patients with bulimia nervosa.

PubMed

Wang, Li; Kong, Qing-Mei; Li, Ke; Li, Xue-Ni; Zeng, Ya-Wei; Chen, Chao; Qian, Ying; Feng, Shi-Jie; Li, Ji-Tao; Su, Yun'Ai; Correll, Christoph U; Mitchell, Philip B; Yan, Chao-Gan; Zhang, Da-Rong; Si, Tian-Mei

2017-11-01

Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large-scale distributed brain regions. These abnormalities contribute to more comprehensive understanding of the neural mechanism underlying pathological eating and body perception in women with bulimia nervosa.

The polygenic risk for bipolar disorder influences brain regional function relating to visual and default state processing of emotional information.

PubMed

Dima, Danai; de Jong, Simone; Breen, Gerome; Frangou, Sophia

2016-01-01

Genome-wise association studies have identified a number of common single-nucleotide polymorphisms (SNPs), each of small effect, associated with risk to bipolar disorder (BD). Several risk-conferring SNPs have been individually shown to influence regional brain activation thus linking genetic risk for BD to altered brain function. The current study examined whether the polygenic risk score method, which models the cumulative load of all known risk-conferring SNPs, may be useful in the identification of brain regions whose function may be related to the polygenic architecture of BD. We calculated the individual polygenic risk score for BD (PGR-BD) in forty-one patients with the disorder, twenty-five unaffected first-degree relatives and forty-six unrelated healthy controls using the most recent Psychiatric Genomics Consortium data. Functional magnetic resonance imaging was used to define task-related brain activation patterns in response to facial affect and working memory processing. We found significant effects of the PGR-BD score on task-related activation irrespective of diagnostic group. There was a negative association between the PGR-BD score and activation in the visual association cortex during facial affect processing. In contrast, the PGR-BD score was associated with failure to deactivate the ventromedial prefrontal region of the default mode network during working memory processing. These results are consistent with the threshold-liability model of BD, and demonstrate the usefulness of the PGR-BD score in identifying brain functional alternations associated with vulnerability to BD. Additionally, our findings suggest that the polygenic architecture of BD is not regionally confined but impacts on the task-dependent recruitment of multiple brain regions.

Advances in neuroimaging of traumatic brain injury and posttraumatic stress disorder

PubMed Central

Van Boven, Robert W.; Harrington, Greg S.; Hackney, David B.; Ebel, Andreas; Gauger, Grant; Bremner, J. Douglas; D’Esposito, Mark; Detre, John A.; Haacke, E. Mark; Jack, Clifford R.; Jagust, William J.; Le Bihan, Denis; Mathis, Chester A.; Mueller, Susanne; Mukherjee, Pratik; Schuff, Norbert; Chen, Anthony; Weiner, Michael W.

2011-01-01

Improved diagnosis and treatment of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are needed for our military and veterans, their families, and society at large. Advances in brain imaging offer important biomarkers of structural, functional, and metabolic information concerning the brain. This article reviews the application of various imaging techniques to the clinical problems of TBI and PTSD. For TBI, we focus on findings and advances in neuroimaging that hold promise for better detection, characterization, and monitoring of objective brain changes in symptomatic patients with combat-related, closed-head brain injuries not readily apparent by standard computed tomography or conventional magnetic resonance imaging techniques. PMID:20104401

Pathological anxiety and function/dysfunction in the brain's fear/defense circuitry.

PubMed

Lang, Peter J; McTeague, Lisa M; Bradley, Margaret M

2014-01-01

Research from the University of Florida Center for the Study of Emotion and Attention aims to develop neurobiological measures that objectively discriminate among symptom patterns in patients with anxiety disorders. From this perspective, anxiety and mood pathologies are considered to be brain disorders, resulting from dysfunction and maladaptive plasticity in the neural circuits that determine fearful/defensive and appetitive/reward behavior (Insel et al., 2010). We review recent studies indicating that an enhanced probe startle reflex during the processing of fear memory cues (mediated by cortico-limbic circuitry and thus indicative of plastic brain changes), varies systematically in strength over a spectrum-wide dimension of anxiety pathology-across and within diagnoses-extending from strong focal fear reactions to a consistently blunted reaction in patients with more generalized anxiety and comorbid mood disorders. Preliminary studies with functional magnetic resonance imaging (fMRI) encourage the hypothesis that fear/defense circuit dysfunction covaries with this same dimension of psychopathology. Plans are described for an extended study of the brain's motivation circuitry in anxiety spectrum patients, with the aim of defining the specifics of circuit dysfunction in severe disorders. A sub-project explores the use of real-time fMRI feedback in circuit analysis and as a modality to up-regulate circuit function in the context of blunted affect.

Lesions causing freezing of gait localize to a cerebellar functional network

PubMed Central

Fasano, Alfonso; Laganiere, Simon E.; Lam, Susy; Fox, Michael D.

2016-01-01

Objective Freezing of gait is a disabling symptom in Parkinson’s disease and related disorders, but the brain regions involved in symptom generation remain unclear. Here we analyze brain lesions causing acute onset freezing of gait to identify regions causally involved in symptom generation. Methods Fourteen cases of lesion-induced freezing of gait were identified from the literature and lesions were mapped to a common brain atlas. Because lesion-induced symptoms can come from sites connected to the lesion location, not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has been recently shown to identify regions involved in symptom generation across a variety of lesion-induced disorders. Results Lesion location was heterogeneous and no single region could be considered necessary for symptom generation. However, over 90% (13/14) of lesions were functionally connected to a focal area in the dorsal medial cerebellum. This cerebellar area overlapped previously recognized regions that are activated by locomotor tasks, termed the cerebellar locomotor region. Connectivity to this region was specific to lesions causing freezing of gait compared to lesions causing other movement disorders (hemichorea or asterixis). Interpretation Lesions causing freezing of gait are located within a common functional network characterized by connectivity to the cerebellar locomotor region. These results based on causal brain lesions complement prior neuroimaging studies in Parkinson’s disease patients, advancing our understanding of the brain regions involved in freezing of gait. PMID:28009063

Abnormal Functional Connectivity in Autism Spectrum Disorders during Face Processing

ERIC Educational Resources Information Center

Kleinhans, Natalia M.; Richards, Todd; Sterling, Lindsey; Stegbauer, Keith C.; Mahurin, Roderick; Johnson, L. Clark; Greenson, Jessica; Dawson, Geraldine; Aylward, Elizabeth

2008-01-01

Abnormalities in the interactions between functionally linked brain regions have been suggested to be associated with the clinical impairments observed in autism spectrum disorders (ASD). We investigated functional connectivity within the limbic system during face identification; a primary component of social cognition, in 19 high-functioning…

Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

PubMed Central

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

2014-01-01

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

Decreased Functional Brain Connectivity in Adolescents with Internet Addiction

PubMed Central

Hong, Soon-Beom; Zalesky, Andrew; Cocchi, Luca; Fornito, Alex; Choi, Eun-Jung; Kim, Ho-Hyun; Suh, Jeong-Eun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung

2013-01-01

Background Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry. Methods Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures. Results Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (∼24% with prefrontal and ∼27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio. Conclusions Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology. PMID:23451272

Affection of Fundamental Brain Activity By Using Sounds For Patients With Prosodic Disorders: A Pilot Study

NASA Astrophysics Data System (ADS)

Imai, Emiko; Katagiri, Yoshitada; Seki, Keiko; Kawamata, Toshio

2011-06-01

We present a neural model of the production of modulated speech streams in the brain, referred to as prosody, which indicates the limbic structure essential for producing prosody both linguistically and emotionally. This model suggests that activating the fundamental brain including monoamine neurons at the basal ganglia will potentially contribute to helping patients with prosodic disorders coming from functional defects of the fundamental brain to overcome their speech problem. To establish effective clinical treatment for such prosodic disorders, we examine how sounds affect the fundamental activity by using electroencephalographic measurements. Throughout examinations with various melodious sounds, we found that some melodies with lilting rhythms successfully give rise to the fast alpha rhythms at the electroencephalogram which reflect the fundamental brain activity without any negative feelings.

Repeat neurobehavioral study of borderline personality disorder.

PubMed Central

van Reekum, R; Links, P S; Finlayson, M A; Boyle, M; Boiago, I; Ostrander, L A; Moustacalis, E

1996-01-01

Previous research has tentatively identified a large subgroup of patients with borderline personality disorder (BPD) with histories of developmental or acquired brain insults. Similarly, these studies have demonstrated a possible biological correlation between the severity of BPD and the number of previous brain insults. The possibility of frontal system cognitive dysfunction in BPD has been raised. This single-blind, case-control study of BPD showed that 13 of 24 subjects with BPD had suffered a brain insult. Correlations between neurodevelopmental/acquired brain injury score and the diagnostic interview for borderline (DIB) score (r = 0.47), and between frontal system cognitive functioning and DIB score (r = -0.37) were seen. Neurocognitive testing and comparison with a cohort of subjects with traumatic brain injury (TBI) showed a pattern of similar cognitive functioning between the 2 groups, with the only differences on individual tests being in the direction of worse functioning in the group with BPD on 2 tasks. These results support the hypotheses described above. The main limitation reflects the low numbers of subjects. PMID:8580113

Biomarkers for Success: Using Neuroimaging to Predict Relapse and Develop Brain Stimulation Treatments for Cocaine-Dependent Individuals.

PubMed

Hanlon, C A; Dowdle, L T; Jones, J L

2016-01-01

Cocaine dependence is one of the most difficult substance use disorders to treat. While the powerful effects of cocaine use on behavior were documented in the 19th century, it was not until the late 20th century that we realized cocaine use was affecting brain tissue and function. Following a brief introduction (Section 1), this chapter will summarize our current knowledge regarding alterations in neural circuit function typically observed in chronic cocaine users (Section 2) and highlight an emerging body of literature which suggests that pretreatment limbic circuit activity may be a reliable predictor of clinical outcomes among individuals seeking treatment for cocaine (Section 3). Finally, as the field of addiction research strives to translate this neuroimaging data into something clinically meaningful, we will highlight several new brain stimulation approaches which utilize functional brain imaging data to design noninvasive brain stimulation interventions for individuals seeking treatment for substance dependence disorders (Section 4). © 2016 Elsevier Inc. All rights reserved.

Assessing Language Dominance with Functional MRI: The Role of Control Tasks and Statistical Analysis

ERIC Educational Resources Information Center

Dodoo-Schittko, Frank; Rosengarth, Katharina; Doenitz, Christian; Greenlee, Mark W.

2012-01-01

There is a discrepancy between the brain regions revealed by functional neuroimaging techniques and those brain regions where a loss of function, either by lesion or by electrocortical stimulation, induces language disorders. To differentiate between essential and non-essential language-related processes, we investigated the effects of linguistic…

Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

PubMed

Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

2016-09-01

Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Absence of sex differences in mental rotation performance in autism spectrum disorder.

PubMed

Rohde, Melanie S; Georgescu, Alexandra L; Vogeley, Kai; Fimmers, Rolf; Falter-Wagner, Christine M

2017-08-01

Mental rotation is one of the most investigated cognitive functions showing consistent sex differences. The 'Extreme Male Brain' hypothesis attributes the cognitive profile of individuals with autism spectrum disorder to an extreme version of the male cognitive profile. Previous investigations focused almost exclusively on males with autism spectrum disorder with only limited implications for affected females. This study is the first testing a sample of 12 female adults with high-functioning autism spectrum disorder compared to 14 males with autism spectrum disorder, 12 typically developing females and 14 typically developing males employing a computerised version of the mental rotation test. Reaction time and accuracy served as dependent variables. Their linear relationship with degree of rotation allows separation of rotational aspects of the task, indicated by slopes of the psychometric function, and non-rotational aspects, indicated by intercepts of the psychometric function. While the typical and expected sex difference for rotational task aspects was corroborated in typically developing individuals, no comparable sex difference was found in autism spectrum disorder individuals. Autism spectrum disorder and typically developing individuals did not differ in mental rotation performance. This finding does not support the extreme male brain hypothesis of autism.

Emerging Roles of BAI Adhesion-GPCRs in Synapse Development and Plasticity.

PubMed

Duman, Joseph G; Tu, Yen-Kuei; Tolias, Kimberley F

2016-01-01

Synapses mediate communication between neurons and enable the brain to change in response to experience, which is essential for learning and memory. The sites of most excitatory synapses in the brain, dendritic spines, undergo rapid remodeling that is important for neural circuit formation and synaptic plasticity. Abnormalities in synapse and spine formation and plasticity are associated with a broad range of brain disorders, including intellectual disabilities, autism spectrum disorders (ASD), and schizophrenia. Thus, elucidating the mechanisms that regulate these neuronal processes is critical for understanding brain function and disease. The brain-specific angiogenesis inhibitor (BAI) subfamily of adhesion G-protein-coupled receptors (adhesion-GPCRs) has recently emerged as central regulators of synapse development and plasticity. In this review, we will summarize the current knowledge regarding the roles of BAIs at synapses, highlighting their regulation, downstream signaling, and physiological functions, while noting the roles of other adhesion-GPCRs at synapses. We will also discuss the relevance of BAIs in various neurological and psychiatric disorders and consider their potential importance as pharmacological targets in the treatment of these diseases.

Attention-deficit hyperactivity disorder (ADHD) and tuberous sclerosis complex.

PubMed

D'Agati, Elisa; Moavero, Romina; Cerminara, Caterina; Curatolo, Paolo

2009-10-01

The neurobiological basis of attention-deficit hyperactivity disorder (ADHD) in tuberous sclerosis complex is still largely unknown. Cortical tubers may disrupt several brain networks that control different types of attention. Frontal lobe dysfunction due to seizures or epileptiform electroencephalographic discharges may perturb the development of brain systems that underpin attentional and hyperactive functions during a critical early stage of brain maturation. Comorbidity of attention-deficit hyperactivity disorder (ADHD) with mental retardation and autism spectrum disorders is frequent in children with tuberous sclerosis. Attention-deficit hyperactivity disorder (ADHD) may also reflect a direct effect of the abnormal genetic program. Treatment of children with tuberous sclerosis complex with combined symptoms of attention-deficit hyperactivity disorder (ADHD) and epilepsy may represent a challenge for clinicians, because antiepileptic therapy and drugs used to treat attention-deficit hyperactivity disorder (ADHD) may aggravate the clinical picture of each other.

MicroRNAs in neuronal function and dysfunction

PubMed Central

Im, Heh-In; Kenny, Paul J.

2012-01-01

MicroRNAs (miRNAs) are small noncoding RNA transcripts expressed throughout the brain that can regulate neuronal gene expression at the post-transcriptional level. Here, we provide an overview of the role for miRNAs in brain development and function, and review evidence suggesting that dysfunction in miRNA signaling contributes to neurodevelopment disorders such as Rett and fragile X syndromes, as well as complex behavioral disorders including schizophrenia, depression and drug addiction. A better understanding of how miRNAs influence the development of neuropsychiatric disorders may reveal fundamental insights into the causes of these devastating illnesses and offer novel targets for therapeutic development. PMID:22436491

Research Review: Constraining Heterogeneity--The Social Brain and Its Development in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Pelphrey, Kevin A.; Shultz, Sarah; Hudac, Caitlin M.; Vander Wyk, Brent C.

2011-01-01

The expression of autism spectrum disorder (ASD) is highly heterogeneous, owing to the complex interactions between genes, the brain, and behavior throughout development. Here we present a model of ASD that implicates an early and initial failure to develop the specialized functions of one or more of the set of neuroanatomical structures involved…

[Visual perception and its disorders].

PubMed

Ruf-Bächtiger, L

1989-11-21

It's the brain and not the eye that decides what is perceived. In spite of this fact, quite a lot is known about the functioning of the eye and the first sections of the optic tract, but little about the actual process of perception. Examination of visual perception and its malfunctions relies therefore on certain hypotheses. Proceeding from the model of functional brain systems, variant functional domains of visual perception can be distinguished. Among the more important of these domains are: digit span, visual discrimination and figure-ground discrimination. Evaluation of these functional domains allows us to understand those children with disorders of visual perception better and to develop more effective treatment methods.

Neurosteroid vitamin D system as a nontraditional drug target in neuropsychopharmacology.

PubMed

Stewart, Adam; Wong, Keith; Cachat, Jonathan; Elegante, Marco; Gilder, Tom; Mohnot, Sopan; Wu, Nadine; Minasyan, Anna; Tuohimaa, Pentti; Kalueff, Allan V

2010-09-01

Vitamin D is becoming increasingly recognized as a nontraditional drug target for different brain pathologies. Although widely known for their role in calcium metabolism, vitamin D and its receptor have been linked to several brain disorders, including cognitive decline, epilepsy, affective disorders, and schizophrenia. Here we discuss mounting evidence, and parallel recent clinical and animal behavioral, genetic and pharmacological data to emphasize the emerging role of the neurosteroid vitamin D system in brain function.

Peroxisomes in brain development and function☆

PubMed Central

Berger, Johannes; Dorninger, Fabian; Forss-Petter, Sonja; Kunze, Markus

2016-01-01

Peroxisomes contain numerous enzymatic activities that are important for mammalian physiology. Patients lacking either all peroxisomal functions or a single enzyme or transporter function typically develop severe neurological deficits, which originate from aberrant development of the brain, demyelination and loss of axonal integrity, neuroinflammation or other neurodegenerative processes. Whilst correlating peroxisomal properties with a compilation of pathologies observed in human patients and mouse models lacking all or individual peroxisomal functions, we discuss the importance of peroxisomal metabolites and tissue- and cell type-specific contributions to the observed brain pathologies. This enables us to deconstruct the local and systemic contribution of individual metabolic pathways to specific brain functions. We also review the recently discovered variability of pathological symptoms in cases with unexpectedly mild presentation of peroxisome biogenesis disorders. Finally, we explore the emerging evidence linking peroxisomes to more common neurological disorders such as Alzheimer’s disease, autism and amyotrophic lateral sclerosis. This article is part of a Special Issue entitled: Peroxisomes edited by Ralf Erdmann. PMID:26686055

Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

PubMed

Bock, J; Breuer, S; Poeggel, G; Braun, K

2017-03-01

In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using ( 14 C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

An 'integrative neuroscience' perspective on ADHD: linking cognition, emotion, brain and genetic measures with implications for clinical support.

PubMed

Williams, Leanne M; Tsang, Tracey W; Clarke, Simon; Kohn, Michael

2010-10-01

There remains a translational gap between research findings and their implementation in clinical practice that applies to attention-deficit/hyperactivity disorder (ADHD), as well as to other major disorders of brain health in childhood, adolescence and adulthood. Research studies have identified potential 'markers' to support diagnostic, functional assessment and treatment decisions, but there is little consensus about these markers. Of these potential markers, cognitive measures of thinking functions, such as sustaining attention and associated electrical brain activity, show promise in complementing the clinical management process. Emerging evidence highlights the relevance of emotional, as well as thinking, functions to ADHD. Here, we outline an integrative neuroscience framework for ADHD that offers one means to bring together cognitive measures of thinking functions with measures of emotion, and their brain and genetic correlates. Understanding these measures and the relationships between them is a first step towards the development of tools that will help to assess the heterogeneity of ADHD, and aid in tailoring treatment choices.

A Systematic Review and Meta-analysis of Neuroimaging in Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) Taking Attention-Deficit Hyperactivity Disorder (ADHD) Into Account.

PubMed

Noordermeer, Siri D S; Luman, Marjolein; Oosterlaan, Jaap

2016-03-01

Oppositional defiant disorder (ODD) and conduct disorder (CD) are common behavioural disorders in childhood and adolescence and are associated with brain abnormalities. This systematic review and meta-analysis investigates structural (sMRI) and functional MRI (fMRI) findings in individuals with ODD/CD with and without attention-deficit hyperactivity disorder (ADHD). Online databases were searched for controlled studies, resulting in 12 sMRI and 17 fMRI studies. In line with current models on ODD/CD, studies were classified in hot and cool executive functioning (EF). Both the meta-analytic and narrative reviews showed evidence of smaller brain structures and lower brain activity in individuals with ODD/CD in mainly hot EF-related areas: bilateral amygdala, bilateral insula, right striatum, left medial/superior frontal gyrus, and left precuneus. Evidence was present in both structural and functional studies, and irrespective of the presence of ADHD comorbidity. There is strong evidence that abnormalities in the amygdala are specific for ODD/CD as compared to ADHD, and correlational studies further support the association between abnormalities in the amygdala and ODD/CD symptoms. Besides the left precuneus, there was no evidence for abnormalities in typical cool EF related structures, such as the cerebellum and dorsolateral prefrontal cortex. Resulting areas are associated with emotion-processing, error-monitoring, problem-solving and self-control; areas associated with neurocognitive and behavioural deficits implicated in ODD/CD. Our findings confirm the involvement of hot, and to a smaller extent cool, EF associated brain areas in ODD/CD, and support an integrated model for ODD/CD (e.g. Blair, Development and Psychopathology, 17(3), 865-891, 2005).

Perinatal inflammation and adult psychopathology: From preclinical models to humans.

PubMed

Depino, Amaicha Mara

2018-05-01

Perinatal environment plays a crucial role in brain development and determines its function through life. Epidemiological studies and clinical reports link perinatal exposure to infection and/or immune activation to various psychiatric disorders. In addition, accumulating evidence from animal models shows that perinatal inflammation can affect various behaviors relevant to psychiatric disorders such as schizophrenia, autism, anxiety and depression. Remarkably, the effects on behavior and brain function do not always depend on the type of inflammatory stimulus or the perinatal age targeted, so diverse inflammatory events can have similar consequences on the brain. Moreover, other perinatal environmental factors that affect behavior (e.g. diet and stress) also elicit inflammatory responses. Understanding the interplay between perinatal environment and inflammation on brain development is required to identify the mechanisms through which perinatal inflammation affect brain function in the adult animal. Evidence for the role of the peripheral immune system and glia on perinatal programming of behavior is discussed in this review, along with recent evidence for the role of epigenetic mechanisms affecting gene expression in the brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease.

PubMed

Eyles, Darryl W; Burne, Thomas H J; McGrath, John J

2013-01-01

Increasingly vitamin D deficiency is being associated with a number of psychiatric conditions. In particular for disorders with a developmental basis, such as autistic spectrum disorder and schizophrenia the neurobiological plausibility of this association is strengthened by the preclinical data indicating vitamin D deficiency in early life affects neuronal differentiation, axonal connectivity, dopamine ontogeny and brain structure and function. More recently epidemiological associations have been made between low vitamin D and psychiatric disorders not typically associated with abnormalities in brain development such as depression and Alzheimer's disease. Once again the preclinical findings revealing that vitamin D can regulate catecholamine levels and protect against specific Alzheimer-like pathology increase the plausibility of this link. In this review we have attempted to integrate this clinical epidemiology with potential vitamin D-mediated basic mechanisms. Throughout the review we have highlighted areas where we think future research should focus. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders.

PubMed

O'Donnell, Cian; Gonçalves, J Tiago; Portera-Cailliau, Carlos; Sejnowski, Terrence J

2017-10-11

A leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this one-dimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here, we combined computational simulations with analysis of in vivo two-photon Ca 2+ imaging data from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: (1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; (2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; (3) The direction of circuit alterations in Fmr1 KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher dimensional models that can better capture the multidimensional computational functions of neural circuits.

Beyond excitation/inhibition imbalance in multidimensional models of neural circuit changes in brain disorders

PubMed Central

Gonçalves, J Tiago; Portera-Cailliau, Carlos

2017-01-01

A leading theory holds that neurodevelopmental brain disorders arise from imbalances in excitatory and inhibitory (E/I) brain circuitry. However, it is unclear whether this one-dimensional model is rich enough to capture the multiple neural circuit alterations underlying brain disorders. Here, we combined computational simulations with analysis of in vivo two-photon Ca2+ imaging data from somatosensory cortex of Fmr1 knock-out (KO) mice, a model of Fragile-X Syndrome, to test the E/I imbalance theory. We found that: (1) The E/I imbalance model cannot account for joint alterations in the observed neural firing rates and correlations; (2) Neural circuit function is vastly more sensitive to changes in some cellular components over others; (3) The direction of circuit alterations in Fmr1 KO mice changes across development. These findings suggest that the basic E/I imbalance model should be updated to higher dimensional models that can better capture the multidimensional computational functions of neural circuits. PMID:29019321

Using real-time fMRI brain-computer interfacing to treat eating disorders.

PubMed

Sokunbi, Moses O

2018-05-15

Real-time functional magnetic resonance imaging based brain-computer interfacing (fMRI neurofeedback) has shown encouraging outcomes in the treatment of psychiatric and behavioural disorders. However, its use in the treatment of eating disorders is very limited. Here, we give a brief overview of how to design and implement fMRI neurofeedback intervention for the treatment of eating disorders, considering the basic and essential components. We also attempt to develop potential adaptations of fMRI neurofeedback intervention for the treatment of anorexia nervosa, bulimia nervosa and binge eating disorder. Copyright © 2018 Elsevier B.V. All rights reserved.

Brain function in carriers of a genome-wide supported bipolar disorder variant.

PubMed

Erk, Susanne; Meyer-Lindenberg, Andreas; Schnell, Knut; Opitz von Boberfeld, Carola; Esslinger, Christine; Kirsch, Peter; Grimm, Oliver; Arnold, Claudia; Haddad, Leila; Witt, Stephanie H; Cichon, Sven; Nöthen, Markus M; Rietschel, Marcella; Walter, Henrik

2010-08-01

The neural abnormalities underlying genetic risk for bipolar disorder, a severe, common, and highly heritable psychiatric condition, are largely unknown. An opportunity to define these mechanisms is provided by the recent discovery, through genome-wide association, of a single-nucleotide polymorphism (rs1006737) strongly associated with bipolar disorder within the CACNA1C gene, encoding the alpha subunit of the L-type voltage-dependent calcium channel Ca(v)1.2. To determine whether the genetic risk associated with rs1006737 is mediated through hippocampal function. Functional magnetic resonance imaging study. University hospital. A total of 110 healthy volunteers of both sexes and of German descent in the Hardy-Weinberg equilibrium for rs1006737. Blood oxygen level-dependent signal during an episodic memory task and behavioral and psychopathological measures. Using an intermediate phenotype approach, we show that healthy carriers of the CACNA1C risk variant exhibit a pronounced reduction of bilateral hippocampal activation during episodic memory recall and diminished functional coupling between left and right hippocampal regions. Furthermore, risk allele carriers exhibit activation deficits of the subgenual anterior cingulate cortex, a region repeatedly associated with affective disorders and the mediation of adaptive stress-related responses. The relevance of these findings for affective disorders is supported by significantly higher psychopathology scores for depression, anxiety, obsessive-compulsive thoughts, interpersonal sensitivity, and neuroticism in risk allele carriers, correlating negatively with the observed regional brain activation. Our data demonstrate that rs1006737 or genetic variants in linkage disequilibrium with it are functional in the human brain and provide a neurogenetic risk mechanism for bipolar disorder backed by genome-wide evidence.

Global brain atrophy is associated with physical performance and the risk of falls in older adults with cognitive impairment.

PubMed

Yamada, Minoru; Takechi, Hajime; Mori, Shuhei; Aoyama, Tomoki; Arai, Hidenori

2013-04-01

Falls are common in patients with cognitive disorder. The purpose of this study was to determine whether global brain atrophy is associated with cognitive function, physical performance and fall incidents in older adults with mild cognitive disorder. A total of 31 older adults with mild cognitive disorders (mean age 78.9 ± 7.3 years) were studied, and 10 of them had experienced falls and the others had not in the past 1 year. Cognitive function and physical performance were measured in these patients. Global brain atrophy was determined by the Voxel-Based Specific Regional Analysis System for Alzheimer's Disease software. Fallers showed significantly worse scores than the non-fallers in the Global Brain Atrophy Index, Clock Drawing Test (CDT), Verbal Fluency Test (animal), maximum walking time and Timed Up & Go (TUG) Test. The Global Brain Atrophy Index was correlated with the Verbal Fluency Test (animal; r = -0.522), the Verbal Fluency Test with letter (ka; r = -0.337), CDT (r = -0.547), TUG (r = 0.276) and Five Chair Stands Test (r = 0.303) by age-adjusted correlation analyses. Stepwise regression analysis showed that the Global Brain Atrophy Index (β = 1.265, 95% CI 1.022-1.567) was a significant and independent determinant of falls (R(2) = 0.356, P = 0.003). Global brain atrophy might be indicated as one of the risk factors for falls in older adults with mild cognitive disorders. © 2012 Japan Geriatrics Society.

A psychology of the human brain-gut-microbiome axis.

PubMed

Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

2017-04-01

In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

Connectivity dynamics in typical development and its relationship to autistic traits and autism spectrum disorder.

PubMed

Rashid, Barnaly; Blanken, Laura M E; Muetzel, Ryan L; Miller, Robyn; Damaraju, Eswar; Arbabshirani, Mohammad R; Erhardt, Erik B; Verhulst, Frank C; van der Lugt, Aad; Jaddoe, Vincent W V; Tiemeier, Henning; White, Tonya; Calhoun, Vince

2018-03-30

Recent advances in neuroimaging techniques have provided significant insights into developmental trajectories of human brain function. Characterizations of typical neurodevelopment provide a framework for understanding altered neurodevelopment, including differences in brain function related to developmental disorders and psychopathology. Historically, most functional connectivity studies of typical and atypical development operate under the assumption that connectivity remains static over time. We hypothesized that relaxing stationarity assumptions would reveal novel features of both typical brain development related to children on the autism spectrum. We employed a "chronnectomic" (recurring, time-varying patterns of connectivity) approach to evaluate transient states of connectivity using resting-state functional MRI in a population-based sample of 774 6- to 10-year-old children. Dynamic connectivity was evaluated using a sliding-window approach, and revealed four transient states. Internetwork connectivity increased with age in modularized dynamic states, illustrating an important pattern of connectivity in the developing brain. Furthermore, we demonstrated that higher levels of autistic traits and ASD diagnosis were associated with longer dwell times in a globally disconnected state. These results provide a roadmap to the chronnectomic organization of the developing brain and suggest that characteristics of functional brain connectivity are related to children on the autism spectrum. © 2018 Wiley Periodicals, Inc.

Craving Responses to Methamphetamine and Sexual Visual Cues in Individuals With Methamphetamine Use Disorder After Long-Term Drug Rehabilitation

PubMed Central

Huang, Shucai; Zhang, Zhixue; Dai, Yuanyuan; Zhang, Changcun; Yang, Cheng; Fan, Lidan; Liu, Jun; Hao, Wei; Chen, Hongxian

2018-01-01

Studies utilizing functional magnetic resonance imaging (fMRI) cue-reactivity paradigms have demonstrated that short-term abstinent or current methamphetamine (MA) users have increased brain activity in the ventral striatum, caudate nucleus and medial frontal cortex, when exposed to MA-related visual cues. However, patterns of brain activity following cue-reactivity in subjects with long-term MA abstinence, especially long-term compulsory drug rehabilitation, have not been well studied. To enrich knowledge in this field, functional brain imaging was conducted during a cue-reactivity paradigm task in 28 individuals with MA use disorder following long-term compulsory drug rehabilitation, and 27 healthy control subjects. The results showed that, when compared with controls, individuals with MA use disorder displayed elevated activity in the bilateral medial prefrontal cortex (mPFC) and right lateral posterior cingulate cortex in response to MA-related images. Additionally, the anterior cingulate region of mPFC activation during the MA-related cue-reactivity paradigm was positively correlated with craving alterations and previous frequency of drug use. No significant differences in brain activity in response to pornographic images were found between the two groups. Compared to MA cues, individuals with MA use disorder had increased activation in the occipital lobe when exposed to pornographic cues. In conclusion, the present study indicates that, even after long-term drug rehabilitation, individuals with MA use disorder have unique brain activity when exposed to MA-related cues. Additionally, our results illustrate that the libido brain response might be restored, and that sexual demand might be more robust than drug demand, in individuals with MA use disorder following long-term drug rehabilitation. PMID:29725310

Craving Responses to Methamphetamine and Sexual Visual Cues in Individuals With Methamphetamine Use Disorder After Long-Term Drug Rehabilitation.

PubMed

Huang, Shucai; Zhang, Zhixue; Dai, Yuanyuan; Zhang, Changcun; Yang, Cheng; Fan, Lidan; Liu, Jun; Hao, Wei; Chen, Hongxian

2018-01-01

Studies utilizing functional magnetic resonance imaging (fMRI) cue-reactivity paradigms have demonstrated that short-term abstinent or current methamphetamine (MA) users have increased brain activity in the ventral striatum, caudate nucleus and medial frontal cortex, when exposed to MA-related visual cues. However, patterns of brain activity following cue-reactivity in subjects with long-term MA abstinence, especially long-term compulsory drug rehabilitation, have not been well studied. To enrich knowledge in this field, functional brain imaging was conducted during a cue-reactivity paradigm task in 28 individuals with MA use disorder following long-term compulsory drug rehabilitation, and 27 healthy control subjects. The results showed that, when compared with controls, individuals with MA use disorder displayed elevated activity in the bilateral medial prefrontal cortex (mPFC) and right lateral posterior cingulate cortex in response to MA-related images. Additionally, the anterior cingulate region of mPFC activation during the MA-related cue-reactivity paradigm was positively correlated with craving alterations and previous frequency of drug use. No significant differences in brain activity in response to pornographic images were found between the two groups. Compared to MA cues, individuals with MA use disorder had increased activation in the occipital lobe when exposed to pornographic cues. In conclusion, the present study indicates that, even after long-term drug rehabilitation, individuals with MA use disorder have unique brain activity when exposed to MA-related cues. Additionally, our results illustrate that the libido brain response might be restored, and that sexual demand might be more robust than drug demand, in individuals with MA use disorder following long-term drug rehabilitation.

Brain disease, connectivity, plasticity and cognitive therapy: A neurological view of mental disorders.

PubMed

Lubrini, G; Martín-Montes, A; Díez-Ascaso, O; Díez-Tejedor, E

2018-04-01

Our conception of the mind-brain relationship has evolved from the traditional idea of dualism to current evidence that mental functions result from brain activity. This paradigm shift, combined with recent advances in neuroimaging, has led to a novel definition of brain functioning in terms of structural and functional connectivity. The purpose of this literature review is to describe the relationship between connectivity, brain lesions, cerebral plasticity, and functional recovery. Assuming that brain function results from the organisation of the entire brain in networks, brain dysfunction would be a consequence of altered brain network connectivity. According to this approach, cognitive and behavioural impairment following brain damage result from disrupted functional organisation of brain networks. However, the dynamic and versatile nature of these circuits makes recovering brain function possible. Cerebral plasticity allows for functional reorganisation leading to recovery, whether spontaneous or resulting from cognitive therapy, after brain disease. Current knowledge of brain connectivity and cerebral plasticity provides new insights into normal brain functioning, the mechanisms of brain damage, and functional recovery, which in turn serve as the foundations of cognitive therapy. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Interaction between BDNF rs6265 Met allele and low family cohesion is associated with smaller left hippocampal volume in pediatric bipolar disorder.

PubMed

Zeni, Cristian Patrick; Mwangi, Benson; Cao, Bo; Hasan, Khader M; Walss-Bass, Consuelo; Zunta-Soares, Giovana; Soares, Jair C

2016-01-01

Genetic and environmental factors are implicated in the onset and evolution of pediatric bipolar disorder, and may be associated to structural brain abnormalities. The aim of our study was to assess the impact of the interaction between the Brain-Derived Neurotrophic Factor (BDNF) rs6265 polymorphism and family functioning on hippocampal volumes of children and adolescents with bipolar disorder, and typically-developing controls. We evaluated the family functioning cohesion subscale using the Family Environment Scale-Revised, genotyped the BDNF rs6265 polymorphism, and performed structural brain imaging in 29 children and adolescents with bipolar disorder, and 22 healthy controls. We did not find significant differences between patients with BD or controls in left or right hippocampus volume (p=0.44, and p=0.71, respectively). However, we detected a significant interaction between low scores on the cohesion subscale and the presence of the Met allele at BNDF on left hippocampal volume of patients with bipolar disorder (F=3.4, p=0.043). None of the factors independently (BDNF Val66Met, cohesion scores) was significantly associated with hippocampal volume differences. small sample size, cross-sectional study. These results may lead to a better understanding of the impact of the interaction between genes and environment factors on brain structures associated to bipolar disorder and its manifestations. Copyright © 2015 Elsevier B.V. All rights reserved.

Hepatic Encephalopathy

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Is there "brain OAB" and how can we recognize it? International Consultation on Incontinence-Research Society (ICI-RS) 2017.

PubMed

Apostolidis, Apostolos; Wagg, Adrian; Rahnam A'i, Mohammad S; Panicker, Jalesh N; Vrijens, Desiree; von Gontard, Alexander

2018-02-01

In light of mounting evidence supporting the association of brain regions with the control of urine storage and voiding, the high placebo effect in OAB studies as well as certain anecdotal observations from clinical practice with OAB patients, the role of the brain in OAB was explored. At the ICI-RS 2017 meeting, a panel of Functional Urologists and Basic Scientists presented literature data generating a proposal to discuss whether there is "brain OAB" and how we could recognize it. Existing data point toward organic brain causes of OAB, in particular concerning white matter disease (WMD) and aging, but with currently speculative mechanisms. Imaging techniques have revealed connectivity changes between brain regions which may explain brain-peripheral interactions in OAB patients, further to acknowledged structural and functional changes in the central nervous system (CNS). Furthermore, psychological disorders like stress and depression have been identified as causes of OAB, with animal and human studies proposing a neurochemical and neuroendocrine pathophysiological basis, involving either the serotoninergic system or the hypothalamic-pituitary-adrenal axis. Finally, childhood data suggest that OAB could be a developmental disorder involving the CNS, although childhood OAB could be a different condition than that of adults in many children. Future research should aim to identify the pathogenesis of WMD and the aging processes affecting the brain and the bladder, with possible benefits in prevention strategies, as well as connectivity disorders within the CNS, the pathophysiology of OAB in childhood and the neurochemical pathways connecting affective disorders with OAB. © 2018 Wiley Periodicals, Inc.

Genomic connectivity networks based on the BrainSpan atlas of the developing human brain

NASA Astrophysics Data System (ADS)

Mahfouz, Ahmed; Ziats, Mark N.; Rennert, Owen M.; Lelieveldt, Boudewijn P. F.; Reinders, Marcel J. T.

2014-03-01

The human brain comprises systems of networks that span the molecular, cellular, anatomic and functional levels. Molecular studies of the developing brain have focused on elucidating networks among gene products that may drive cellular brain development by functioning together in biological pathways. On the other hand, studies of the brain connectome attempt to determine how anatomically distinct brain regions are connected to each other, either anatomically (diffusion tensor imaging) or functionally (functional MRI and EEG), and how they change over development. A global examination of the relationship between gene expression and connectivity in the developing human brain is necessary to understand how the genetic signature of different brain regions instructs connections to other regions. Furthermore, analyzing the development of connectivity networks based on the spatio-temporal dynamics of gene expression provides a new insight into the effect of neurodevelopmental disease genes on brain networks. In this work, we construct connectivity networks between brain regions based on the similarity of their gene expression signature, termed "Genomic Connectivity Networks" (GCNs). Genomic connectivity networks were constructed using data from the BrainSpan Transcriptional Atlas of the Developing Human Brain. Our goal was to understand how the genetic signatures of anatomically distinct brain regions relate to each other across development. We assessed the neurodevelopmental changes in connectivity patterns of brain regions when networks were constructed with genes implicated in the neurodevelopmental disorder autism (autism spectrum disorder; ASD). Using graph theory metrics to characterize the GCNs, we show that ASD-GCNs are relatively less connected later in development with the cerebellum showing a very distinct expression of ASD-associated genes compared to other brain regions.

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.

Treatment of Sleep Disorders after Traumatic Brain Injury

PubMed Central

Castriotta, Richard J.; Atanasov, Strahil; Wilde, Mark C.; Masel, Brent E.; Lai, Jenny M.; Kuna, Samuel T.

2009-01-01

Study Objectives: Determine whether treatment of sleep disorders identified in brain injured adults would result in resolution of those sleep disorders and improvement of symptoms and daytime function. Methods: Prospective evaluation of unselected traumatic brain injury patients with nocturnal polysomnography (NPSG), multiple sleep latency test (MSLT), Epworth Sleepiness Scale (ESS), and neuropsychological testing including Psychomotor Vigilance Test (PVT), Profile of Mood States (POMS), and Functional Outcome of Sleep Questionnaire (FOSQ) before and after treatment with continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA), modafinil (200 mg) for narcolepsy and posttraumatic hypersomnia (PTH), or pramipexole (0.375 mg) for periodic limb movements in sleep (PLMS). Setting: Three academic medical centers. Participants: Fifty-seven (57) adults ≥ 3 months post traumatic brain injury (TBI). Measurements And Results: Abnormal sleep studies were found in 22 subjects (39%), of whom 13 (23%) had OSA, 2 (3%) had PTH, 3 (5%) had narcolepsy, 4 (7%) had PLMS, and 12 had objective excessive daytime sleepiness with MSLT score < 10 minutes. Apneas, hypopneas, and snoring were eliminated by CPAP in OSA subjects, but there was no significant change in MSLT scores. Periodic limb movements were eliminated with pramipexole. One of 3 narcolepsy subjects and 1 of 2 PTH subjects had resolution of hypersomnia with modafinil. There was no significant change in FOSQ, POMS, or PVT results after treatment. Conclusions: Treatment of sleep disorders after TBI may result in polysomnographic resolution without change in sleepiness or neuropsychological function. Citation: Castriotta RJ; Atanasov S; Wilde MC; Masel BE; Lai JM; Kuna ST. Treatment of sleep disorders after traumatic brain injury. J Clin Sleep Med 2009;5(2):137-144. PMID:19968047

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

PubMed

Wichmann, Thomas; DeLong, Mahlon R

2016-04-01

Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

Gamma knife radiosurgery in movement disorders: Indications and limitations.

PubMed

Higuchi, Yoshinori; Matsuda, Shinji; Serizawa, Toru

2017-01-01

Functional radiosurgery has advanced steadily during the past half century since the development of the gamma knife technique for treating intractable cancer pain. Applications of radiosurgery for intracranial diseases have increased with a focus on understanding radiobiology. Currently, the use of gamma knife radiosurgery to ablate deep brain structures is not widespread because visualization of the functional targets remains difficult despite the increased availability of advanced neuroimaging technology. Moreover, most existing reports have a small sample size or are retrospective. However, increased experience with intraoperative neurophysiological evaluations in radiofrequency thalamotomy and deep brain stimulation supports anatomical and neurophysiological approaches to the ventralis intermedius nucleus. Two recent prospective studies have promoted the clinical application of functional radiosurgery for movement disorders. For example, unilateral gamma knife thalamotomy is a potential alternative to radiofrequency thalamotomy and deep brain stimulation techniques for intractable tremor patients with contraindications for surgery. Despite the promising efficacy of gamma knife thalamotomy, however, these studies did not include sufficient follow-up to confirm long-term effects. Herein, we review the radiobiology literature, various techniques, and the treatment efficacy of gamma knife radiosurgery for patients with movement disorders. Future research should focus on randomized controlled studies and long-term effects. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Executive function and functional and structural brain differences in middle-age adults with autism spectrum disorder.

PubMed

Braden, B Blair; Smith, Christopher J; Thompson, Amiee; Glaspy, Tyler K; Wood, Emily; Vatsa, Divya; Abbott, Angela E; McGee, Samuel C; Baxter, Leslie C

2017-12-01

There is a rapidly growing group of aging adults with autism spectrum disorder (ASD) who may have unique needs, yet cognitive and brain function in older adults with ASD is understudied. We combined functional and structural neuroimaging and neuropsychological tests to examine differences between middle-aged men with ASD and matched neurotypical (NT) men. Participants (ASD, n = 16; NT, n = 17) aged 40-64 years were well-matched according to age, IQ (range: 83-131), and education (range: 9-20 years). Middle-age adults with ASD made more errors on an executive function task (Wisconsin Card Sorting Test) but performed similarly to NT adults on tests of delayed verbal memory (Rey Auditory Verbal Learning Test) and local visual search (Embedded Figures Task). Independent component analysis of a functional MRI working memory task (n-back) completed by most participants (ASD = 14, NT = 17) showed decreased engagement of a cortico-striatal-thalamic-cortical neural network in older adults with ASD. Structurally, older adults with ASD had reduced bilateral hippocampal volumes, as measured by FreeSurfer. Findings expand our understanding of ASD as a lifelong condition with persistent cognitive and functional and structural brain differences evident at middle-age. Autism Res 2017, 10: 1945-1959. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. We compared cognitive abilities and brain measures between 16 middle-age men with high-functioning autism spectrum disorder (ASD) and 17 typical middle-age men to better understand how aging affects an older group of adults with ASD. Men with ASD made more errors on a test involving flexible thinking, had less activity in a flexible thinking brain network, and had smaller volume of a brain structure related to memory than typical men. We will follow these older adults over time to determine if aging changes are greater for individuals with ASD. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Astrocytes.

ERIC Educational Resources Information Center

Kimelberg, Harold K.; Norenberg, Michael D.

1989-01-01

Describes the astrocytes' function as equal partners with neurons in both the normal and the abnormal brain. Discusses the developmental scaffolds, inert scar tissue, Huntington's disease, psychiatric disorders, and the identification of these brain cells. (RT)

Functional Magnetic Resonance Imaging of Chronic Dysarthric Speech after Childhood Brain Injury: Reliance on a Left-Hemisphere Compensatory Network

ERIC Educational Resources Information Center

Morgan, Angela T.; Masterton, Richard; Pigdon, Lauren; Connelly, Alan; Liegeois, Frederique J.

2013-01-01

Severe and persistent speech disorder, dysarthria, may be present for life after brain injury in childhood, yet the neural correlates of this chronic disorder remain elusive. Although abundant literature is available on language reorganization after lesions in childhood, little is known about the capacity of motor speech networks to reorganize…

BDNF val66met modulates the association between childhood trauma, cognitive and brain abnormalities in psychoses.

PubMed

Aas, Monica; Haukvik, Unn K; Djurovic, Srdjan; Bergmann, Ørjan; Athanasiu, Lavinia; Tesli, Martin S; Hellvin, Tone; Steen, Nils Eiel; Agartz, Ingrid; Lorentzen, Steinar; Sundet, Kjetil; Andreassen, Ole A; Melle, Ingrid

2013-10-01

Brain derived neurotrophic factor (BDNF) is important for brain development and plasticity, and here we tested if the functional BDNF val66met variant modulates the association between high levels of childhood abuse, cognitive function, and brain abnormalities in psychoses. 249 patients with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were consecutively recruited to the TOP research study (mean±age: 30.7±10.9; gender: 49% males). History of childhood trauma was obtained using the Childhood Trauma Questionnaire. Cognitive function was assessed through a standardized neuropsychological test battery. BDNF val66met was genotyped using standardized procedures. A sub-sample of n=106 Caucasians with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder (mean±age: 32.67±10.85; 49% males) had data on sMRI. Carriers of the Methionine (met) allele exposed to high level of childhood abuse demonstrated significantly poorer cognitive functioning compared to homozygotic Valine (val/val) carriers. Taking in consideration multiple testing, using a more conservative p value, this was still shown for physical abuse and emotional abuse, as well as a trend level for sexual abuse. Further, met carriers exposed to high level of childhood sexual abuse showed reduced right hippocampal volume (r(2)=0.43; p=0.008), and larger right and left lateral ventricles (r(2)=0.37; p=0.002, and r(2)=0.27; p=0.009, respectively). Our findings were independent of age, gender, diagnosis and intracranial volume. Our data demonstrate that in patients with psychoses, met carriers of the BDNF val66met with high level of childhood abuse have more cognitive and brain abnormalities than all other groups. © 2013.

Childhood maltreatment is associated with a sex-dependent functional reorganization of a brain inhibitory control network.

PubMed

Elton, Amanda; Tripathi, Shanti P; Mletzko, Tanja; Young, Jonathan; Cisler, Josh M; James, G Andrew; Kilts, Clinton D

2014-04-01

Childhood adversity represents a major risk factor for drug addiction and other mental disorders. However, the specific mechanisms by which childhood adversity impacts human brain organization to confer greater vulnerability for negative outcomes in adulthood is largely unknown. As an impaired process in drug addiction, inhibitory control of behavior was investigated as a target of childhood maltreatment (abuse and neglect). Forty adults without Axis-I psychiatric disorders (21 females) completed a Childhood Trauma Questionnaire (CTQ) and underwent functional MRI (fMRI) while performing a stop-signal task. A group independent component analysis identified a putative brain inhibitory control network. Graph theoretical analyses and structural equation modeling investigated the impact of childhood maltreatment on the functional organization of this neural processing network. Graph theory outcomes revealed sex differences in the relationship between network functional connectivity and inhibitory control which were dependent on the severity of childhood maltreatment exposure. A network effective connectivity analysis indicated that a maltreatment dose-related negative modulation of dorsal anterior cingulate (dACC) activity by the left inferior frontal cortex (IFC) predicted better response inhibition and lesser attention deficit hyperactivity disorder (ADHD) symptoms in females, but poorer response inhibition and greater ADHD symptoms in males. Less inhibition of the right IFC by dACC in males with higher CTQ scores improved inhibitory control ability. The childhood maltreatment-related reorganization of a brain inhibitory control network provides sex-dependent mechanisms by which childhood adversity may confer greater risk for drug use and related disorders and by which adaptive brain responses protect individuals from this risk factor. Copyright © 2013 Wiley Periodicals, Inc.

Clinical utility of resting-state functional connectivity magnetic resonance imaging for mood and cognitive disorders.

PubMed

Takamura, T; Hanakawa, T

2017-07-01

Although functional magnetic resonance imaging (fMRI) has long been used to assess task-related brain activity in neuropsychiatric disorders, it has not yet become a widely available clinical tool. Resting-state fMRI (rs-fMRI) has been the subject of recent attention in the fields of basic and clinical neuroimaging research. This method enables investigation of the functional organization of the brain and alterations of resting-state networks (RSNs) in patients with neuropsychiatric disorders. Rs-fMRI does not require participants to perform a demanding task, in contrast to task fMRI, which often requires participants to follow complex instructions. Rs-fMRI has a number of advantages over task fMRI for application with neuropsychiatric patients, for example, although applications of task fMR to participants for healthy are easy. However, it is difficult to apply these applications to patients with psychiatric and neurological disorders, because they may have difficulty in performing demanding cognitive task. Here, we review the basic methodology and analysis techniques relevant to clinical studies, and the clinical applications of the technique for examining neuropsychiatric disorders, focusing on mood disorders (major depressive disorder and bipolar disorder) and dementia (Alzheimer's disease and mild cognitive impairment).

The social brain in psychiatric and neurological disorders

PubMed Central

Kennedy, Daniel P.; Adolphs, Ralph

2013-01-01

Psychiatric and neurological disorders have historically provided key insights into the structure-function relationships that subserve human social cognition and behavior, informing the concept of the ‘social brain’. In this review, we take stock of the current status of this concept, retaining a focus on disorders that impact social behavior. We discuss how the social brain, social cognition, and social behavior are interdependent, and emphasize the important role of development and compensation. We suggest that the social brain, and its dysfunction and recovery, must be understood not in terms of specific structures, but rather in terms of their interaction in large-scale networks. PMID:23047070

Pharmacological treatment of sleep disorders and its relationship with neuroplasticity.

PubMed

Abad, Vivien C; Guilleminault, Christian

2015-01-01

Sleep and wakefulness are regulated by complex brain circuits located in the brain stem, thalamus, subthalamus, hypothalamus, basal forebrain, and cerebral cortex. Wakefulness and NREM and REM sleep are modulated by the interactions between neurotransmitters that promote arousal and neurotransmitters that promote sleep. Various lines of evidence suggest that sleep disorders may negatively affect neuronal plasticity and cognitive function. Pharmacological treatments may alleviate these effects but may also have adverse side effects by themselves. This chapter discusses the relationship between sleep disorders, pharmacological treatments, and brain plasticity, including the treatment of insomnia, hypersomnias such as narcolepsy, restless legs syndrome (RLS), obstructive sleep apnea (OSA), and parasomnias.

Are the Gut Bacteria Telling Us to Eat or Not to Eat? Reviewing the Role of Gut Microbiota in the Etiology, Disease Progression and Treatment of Eating Disorders

PubMed Central

Lam, Yan Y.; Maguire, Sarah; Palacios, Talia; Caterson, Ian D.

2017-01-01

Traditionally recognized as mental illnesses, eating disorders are increasingly appreciated to be biologically-driven. There is a growing body of literature that implicates a role of the gut microbiota in the etiology and progression of these conditions. Gut bacteria may act on the gut–brain axis to alter appetite control and brain function as part of the genesis of eating disorders. As the illnesses progress, extreme feeding patterns and psychological stress potentially feed back to the gut ecosystem that can further compromise physiological, cognitive, and social functioning. Given the established causality between dysbiosis and metabolic diseases, an altered gut microbial profile is likely to play a role in the co-morbidities of eating disorders with altered immune function, short-chain fatty acid production, and the gut barrier being the key mechanistic links. Understanding the role of the gut ecosystem in the pathophysiology of eating disorders will provide critical insights into improving current treatments and developing novel microbiome-based interventions that will benefit patients with eating disorders. PMID:28613252

Are the Gut Bacteria Telling Us to Eat or Not to Eat? Reviewing the Role of Gut Microbiota in the Etiology, Disease Progression and Treatment of Eating Disorders.

PubMed

Lam, Yan Y; Maguire, Sarah; Palacios, Talia; Caterson, Ian D

2017-06-14

Traditionally recognized as mental illnesses, eating disorders are increasingly appreciated to be biologically-driven. There is a growing body of literature that implicates a role of the gut microbiota in the etiology and progression of these conditions. Gut bacteria may act on the gut-brain axis to alter appetite control and brain function as part of the genesis of eating disorders. As the illnesses progress, extreme feeding patterns and psychological stress potentially feed back to the gut ecosystem that can further compromise physiological, cognitive, and social functioning. Given the established causality between dysbiosis and metabolic diseases, an altered gut microbial profile is likely to play a role in the co-morbidities of eating disorders with altered immune function, short-chain fatty acid production, and the gut barrier being the key mechanistic links. Understanding the role of the gut ecosystem in the pathophysiology of eating disorders will provide critical insights into improving current treatments and developing novel microbiome-based interventions that will benefit patients with eating disorders.

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.

Insomnia Disorder and Brain's Default-Mode Network.

PubMed

Marques, Daniel Ruivo; Gomes, Ana Allen; Caetano, Gina; Castelo-Branco, Miguel

2018-06-09

Insomnia disorder (ID) is a prevalent sleep disorder that significantly compromises the physical and mental health of individuals. This article reviews novel approaches in the study of brain networks and impaired function in ID through the application of modern neuroimaging techniques such as functional magnetic resonance imaging (fMRI). The default-mode network (DMN) is presumed to be correlated with self-referential information processing, and it appears to be altered or unbalanced in insomnia. A growing body of evidence suggests the lack of deactivation of brain regions comprising the DMN when insomnia patients are at rest. Moreover, core areas of the DMN demonstrate greater activation in insomnia patients when compared to healthy controls in self-referential related tasks. Despite the few studies on the topic, underpinning the correlation between abnormal DMN activity and ID deserves further attention in the future. Implications for therapeutics are briefly outlined.

Cognitive Remediation: Potential Novel Brain-Based Treatment for Bipolar Disorder in Children and Adolescents

PubMed Central

Dickstein, Daniel P.; Cushman, Grace K.; Kim, Kerri L.; Weissman, Alexandra B.; Wegbreit, Ezra

2015-01-01

Bipolar disorder (BD) is among the most impairing psychiatric disorders affecting children and adolescents, despite our best psychopharmacological and psychotherapeutic treatments. Cognitive remediation, defined as a behavioral intervention designed to improve cognitive functions so as to reduce psychiatric illness, is an emerging brain-based treatment approach that has thus far not been studied in pediatric BD. The present article reviews the basic principles of cognitive remediation, describes what is known about cognitive remediation in psychiatric disorders, and delineates potential brain/behavior alterations implicated in pediatric BD that might be targets for cognitive remediation. Emerging data shows that cognitive remediation may be useful in children and adults with schizophrenia, ADHD, and anxiety disorders, and in adults with BD. Potential targets for cognitive remediation in pediatric BD include face processing, response inhibition, frustration, and cognitive flexibility. Further study is warranted to determine if cognitive remediation for these targets, or others, may serve as a novel, brain-based treatment for pediatric BD. PMID:26135596

[Neuropsychology of Tourette's disorder: cognition, neuroimaging and creativity].

PubMed

Espert, R; Gadea, M; Alino, M; Oltra-Cucarella, J

2017-02-24

Tourette's disorder is the result of fronto-striatal brain dysfunction affecting people of all ages, with a debut in early childhood and continuing into adolescence and adulthood. This article reviews the main cognitive, functional neuroimaging and creativity-related studies in a disorder characterized by an excess of dopamine in the brain. Given the special cerebral configuration of these patients, neuropsychological alterations, especially in executive functions, should be expected. However, the findings are inconclusive and are conditioned by factors such as comorbidity with attention deficit hyperactivity disorder and obsessive-compulsive disorder, age or methodological variables. On the other hand, the neuroimaging studies carried out over the last decade have been able to explain the clinical symptoms of Tourette's disorder patients, with special relevance for the supplementary motor area and the anterior cingulate gyrus. Finally, although there is no linear relationship between excess of dopamine and creativity, the scientific literature emphasizes an association between Tourette's disorder and musical creativity, which could be translated into intervention programs based on music.

Co-altered functional networks and brain structure in unmedicated patients with bipolar and major depressive disorders.

PubMed

He, Hao; Sui, Jing; Du, Yuhui; Yu, Qingbao; Lin, Dongdong; Drevets, Wayne C; Savitz, Jonathan B; Yang, Jian; Victor, Teresa A; Calhoun, Vince D

2017-12-01

Bipolar disorder (BD) and major depressive disorder (MDD) share similar clinical characteristics that often obscure the diagnostic distinctions between their depressive conditions. Both functional and structural brain abnormalities have been reported in these two disorders. However, the direct link between altered functioning and structure in these two diseases is unknown. To elucidate this relationship, we conducted a multimodal fusion analysis on the functional network connectivity (FNC) and gray matter density from MRI data from 13 BD, 40 MDD, and 33 matched healthy controls (HC). A data-driven fusion method called mCCA+jICA was used to identify the co-altered FNC and gray matter components. Comparing to HC, BD exhibited reduced gray matter density in the parietal and occipital cortices, which correlated with attenuated functional connectivity within sensory and motor networks, as well as hyper-connectivity in regions that are putatively engaged in cognitive control. In addition, lower gray matter density was found in MDD in the amygdala and cerebellum. High accuracy in discriminating across groups was also achieved by trained classification models, implying that features extracted from the fusion analysis hold the potential to ultimately serve as diagnostic biomarkers for mood disorders.

Network effects of deep brain stimulation

PubMed Central

Alhourani, Ahmad; McDowell, Michael M.; Randazzo, Michael J.; Wozny, Thomas A.; Kondylis, Efstathios D.; Lipski, Witold J.; Beck, Sarah; Karp, Jordan F.; Ghuman, Avniel S.

2015-01-01

The ability to differentially alter specific brain functions via deep brain stimulation (DBS) represents a monumental advance in clinical neuroscience, as well as within medicine as a whole. Despite the efficacy of DBS in the treatment of movement disorders, for which it is often the gold-standard therapy when medical management becomes inadequate, the mechanisms through which DBS in various brain targets produces therapeutic effects is still not well understood. This limited knowledge is a barrier to improving efficacy and reducing side effects in clinical brain stimulation. A field of study related to assessing the network effects of DBS is gradually emerging that promises to reveal aspects of the underlying pathophysiology of various brain disorders and their response to DBS that will be critical to advancing the field. This review summarizes the nascent literature related to network effects of DBS measured by cerebral blood flow and metabolic imaging, functional imaging, and electrophysiology (scalp and intracranial electroencephalography and magnetoencephalography) in order to establish a framework for future studies. PMID:26269552

Large-scale topology and the default mode network in the mouse connectome

PubMed Central

Stafford, James M.; Jarrett, Benjamin R.; Miranda-Dominguez, Oscar; Mills, Brian D.; Cain, Nicholas; Mihalas, Stefan; Lahvis, Garet P.; Lattal, K. Matthew; Mitchell, Suzanne H.; David, Stephen V.; Fryer, John D.; Nigg, Joel T.; Fair, Damien A.

2014-01-01

Noninvasive functional imaging holds great promise for serving as a translational bridge between human and animal models of various neurological and psychiatric disorders. However, despite a depth of knowledge of the cellular and molecular underpinnings of atypical processes in mouse models, little is known about the large-scale functional architecture measured by functional brain imaging, limiting translation to human conditions. Here, we provide a robust processing pipeline to generate high-resolution, whole-brain resting-state functional connectivity MRI (rs-fcMRI) images in the mouse. Using a mesoscale structural connectome (i.e., an anterograde tracer mapping of axonal projections across the mouse CNS), we show that rs-fcMRI in the mouse has strong structural underpinnings, validating our procedures. We next directly show that large-scale network properties previously identified in primates are present in rodents, although they differ in several ways. Last, we examine the existence of the so-called default mode network (DMN)—a distributed functional brain system identified in primates as being highly important for social cognition and overall brain function and atypically functionally connected across a multitude of disorders. We show the presence of a potential DMN in the mouse brain both structurally and functionally. Together, these studies confirm the presence of basic network properties and functional networks of high translational importance in structural and functional systems in the mouse brain. This work clears the way for an important bridge measurement between human and rodent models, enabling us to make stronger conclusions about how regionally specific cellular and molecular manipulations in mice relate back to humans. PMID:25512496

Puzzling Out Synaptic Vesicle 2 Family Members Functions.

PubMed

Bartholome, Odile; Van den Ackerveken, Priscilla; Sánchez Gil, Judit; de la Brassinne Bonardeaux, Orianne; Leprince, Pierre; Franzen, Rachelle; Rogister, Bernard

2017-01-01

Synaptic vesicle proteins 2 (SV2) were discovered in the early 80s, but the clear demonstration that SV2A is the target of efficacious anti-epileptic drugs from the racetam family stimulated efforts to improve understanding of its role in the brain. Many functions have been suggested for SV2 proteins including ions or neurotransmitters transport or priming of SVs. Moreover, several recent studies highlighted the link between SV2 and different neuronal disorders such as epilepsy, Schizophrenia (SCZ), Alzheimer's or Parkinson's disease. In this review article, we will summarize our present knowledge on SV2A function(s) and its potential role(s) in the pathophysiology of various brain disorders.

Puzzling Out Synaptic Vesicle 2 Family Members Functions

PubMed Central

Bartholome, Odile; Van den Ackerveken, Priscilla; Sánchez Gil, Judit; de la Brassinne Bonardeaux, Orianne; Leprince, Pierre; Franzen, Rachelle; Rogister, Bernard

2017-01-01

Synaptic vesicle proteins 2 (SV2) were discovered in the early 80s, but the clear demonstration that SV2A is the target of efficacious anti-epileptic drugs from the racetam family stimulated efforts to improve understanding of its role in the brain. Many functions have been suggested for SV2 proteins including ions or neurotransmitters transport or priming of SVs. Moreover, several recent studies highlighted the link between SV2 and different neuronal disorders such as epilepsy, Schizophrenia (SCZ), Alzheimer’s or Parkinson’s disease. In this review article, we will summarize our present knowledge on SV2A function(s) and its potential role(s) in the pathophysiology of various brain disorders. PMID:28588450

Pathways of Polyunsaturated Fatty Acid Utilization: Implications for Brain Function in Neuropsychiatric Health and Disease

PubMed Central

Liu, Joanne J.; Green, Pnina; Mann, J. John; Rapoport, Stanley I.; Sublette, M. Elizabeth

2014-01-01

Essential polyunsaturated fatty acids (PUFAs) have profound effects on brain development and function. Abnormalities of PUFA status have been implicated in neuropsychiatric diseases such as major depression, bipolar disorder, schizophrenia, Alzheimer’s disease, and attention deficit hyperactivity disorder. Pathophysiologic mechanisms could involve not only suboptimal PUFA intake, but also metabolic and genetic abnormalities, defective hepatic metabolism, and problems with diffusion and transport. This article provides an overview of physiologic factors regulating PUFA utilization, highlighting their relevance to neuropsychiatric disease. PMID:25498862

Dynamic functional connectivity reveals altered variability in functional connectivity among patients with major depressive disorder.

PubMed

Demirtaş, Murat; Tornador, Cristian; Falcón, Carles; López-Solà, Marina; Hernández-Ribas, Rosa; Pujol, Jesús; Menchón, José M; Ritter, Petra; Cardoner, Narcis; Soriano-Mas, Carles; Deco, Gustavo

2016-08-01

Resting-state fMRI (RS-fMRI) has become a useful tool to investigate the connectivity structure of mental health disorders. In the case of major depressive disorder (MDD), recent studies regarding the RS-fMRI have found abnormal connectivity in several regions of the brain, particularly in the default mode network (DMN). Thus, the relevance of the DMN to self-referential thoughts and ruminations has made the use of the resting-state approach particularly important for MDD. The majority of such research has relied on the grand averaged functional connectivity measures based on the temporal correlations between the BOLD time series of various brain regions. We, in our study, investigated the variations in the functional connectivity over time at global and local level using RS-fMRI BOLD time series of 27 MDD patients and 27 healthy control subjects. We found that global synchronization and temporal stability were significantly increased in the MDD patients. Furthermore, the participants with MDD showed significantly increased overall average (static) functional connectivity (sFC) but decreased variability of functional connectivity (vFC) within specific networks. Static FC increased to predominance among the regions pertaining to the default mode network (DMN), while the decreased variability of FC was observed in the connections between the DMN and the frontoparietal network. Hum Brain Mapp 37:2918-2930, 2016. © 2016 Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

The microbiota-gut-brain axis as a key regulator of neural function and the stress response: Implications for human and animal health.

PubMed

Wiley, N C; Dinan, T G; Ross, R P; Stanton, C; Clarke, G; Cryan, J F

2017-07-01

The brain-gut-microbiota axis comprises an extensive communication network between the brain, the gut, and the microbiota residing there. Development of a diverse gut microbiota is vital for multiple features of behavior and physiology, as well as many fundamental aspects of brain structure and function. Appropriate early-life assembly of the gut microbiota is also believed to play a role in subsequent emotional and cognitive development. If the composition, diversity, or assembly of the gut microbiota is impaired, this impairment can have a negative impact on host health and lead to disorders such as obesity, diabetes, inflammatory diseases, and even potentially neuropsychiatric illnesses, including anxiety and depression. Therefore, much research effort in recent years has focused on understanding the potential of targeting the intestinal microbiota to prevent and treat such disorders. This review aims to explore the influence of the gut microbiota on host neural function and behavior, particularly those of relevance to stress-related disorders. The involvement of microbiota in diverse neural functions such as myelination, microglia function, neuronal morphology, and blood-brain barrier integrity across the life span, from early life to adolescence to old age, will also be discussed. Nurturing an optimal gut microbiome may also prove beneficial in animal science as a means to manage stressful situations and to increase productivity of farm animals. The implications of these observations are manifold, and researchers are hopeful that this promising body of preclinical work can be successfully translated to the clinic and beyond.

Early executive function deficit in preterm children and its association with neurodevelopmental disorders in childhood: a literature review.

PubMed

Sun, Jing; Buys, Nicholas

2012-01-01

The purpose of this study is to examine the association of deficits of executive function (EF) and neurodevelopmental disorders in preterm children and the potential of assessing EF in infants as means of early identification. EF refers to a collection of related but somewhat discrete abilities, the main ones being working memory, inhibition, and planning. There is a general consensus that EF governs goal-directed behavior that requires holding those plans or programs on-line until executed, inhibiting irrelevant action and planning a sequence of actions. EF plays an essential role in cognitive development and is vital to individual social and intellectual success. Most researchers believe in the coordination and integrate cognitive-perceptual processes in relation to time and space, thus regulating higher-order cognitive processes, such as problem solving, reasoning, logical and flexible thinking, and decision-making. The importance of the maturation of the frontal lobe, particularly the prefrontal cortex, to the development of EF in childhood has been emphasized. Therefore, any abnormal development in the prefrontal lobes of infants and children could be expected to result in significant deficits in cognitive functioning. As this is a late-maturing part of the brain, various neurodevelopmental disorders, such as autism spectrum disorders, attention deficit hyperactivity disorder, language disorders, and schizophrenia, as well as acquired disorders of the right brain (and traumatic brain injury) impair EF, and the prefrontal cortex may be particularly susceptible to delayed development in these populations. The deficits of EF in infants are persistent into childhood and related to neurodevelopmental disorders in childhood and adolescence.

Motor and somatosensory conversion disorder: a functional unawareness syndrome?

PubMed

Perez, David L; Barsky, Arthur J; Daffner, Kirk; Silbersweig, David A

2012-01-01

Although conversion disorder is closely connected to the origins of neurology and psychiatry, it remains poorly understood. In this article, the authors discuss neural and clinical parallels between lesional unawareness disorders and unilateral motor and somatosensory conversion disorder, emphasizing functional neuroimaging/disease correlates. Authors suggest that a functional-unawareness neurobiological framework, mediated by right hemisphere-lateralized, large-scale brain network dysfunction, may play a significant role in the neurobiology of conversion disorder. The perigenual anterior cingulate and the posterior parietal cortices are detailed as important in disease pathophysiology. Further investigations will refine the functional-unawareness concept, clarify the role of affective circuits, and delineate the process through which functional neurologic symptoms emerge.

Genetic disorders of thyroid metabolism and brain development

PubMed Central

Kurian, Manju A; Jungbluth, Heinz

2014-01-01

Normal thyroid metabolism is essential for human development, including the formation and functioning of the central and peripheral nervous system. Disorders of thyroid metabolism are increasingly recognized within the spectrum of paediatric neurological disorders. Both hypothyroid and hyperthyroid disease states (resulting from genetic and acquired aetiologies) can lead to characteristic neurological syndromes, with cognitive delay, extrapyramidal movement disorders, neuropsychiatric symptoms, and neuromuscular manifestations. In this review, the neurological manifestations of genetic disorders of thyroid metabolism are outlined, with particular focus on Allan-Herndon-Dudley syndrome and benign hereditary chorea. We report in detail the clinical features, major neurological and neuropsychiatric manifestations, molecular genetic findings, disease mechanisms, and therapeutic strategies for these emerging genetic ‘brain-thyroid’ disorders. PMID:24665922

Neural Systems Approaches to Understanding Major Depressive Disorder: An Intrinsic Functional Organization Perspective

PubMed Central

Hamilton, J. Paul; Chen, Michael C.; Gotlib, Ian H.

2012-01-01

Recent research detailing the intrinsic functional organization of the brain provides a unique and useful framework to gain a better understanding of the neural bases of Major Depressive Disorder (MDD). In this review, we first present a brief history of neuroimaging research that has increased our understanding of the functional macro-architecture of the brain. From this macro-architectural perspective, we examine the extant body of functional neuroimaging research assessing MDD with a specific emphasis on the contributions of default-mode, executive, and salience networks in this debilitating disorder. Next, we describe recent investigations conducted in our laboratory in which we explicitly adopt a neural-systems perspective in examining the relations among these networks in MDD. Finally, we offer directions for future research that we believe will facilitate the development of more detailed and integrative models of neural dysfunction in depression. PMID:23477309

Schizophrenia: A Systemic Disorder

PubMed Central

Kirkpatrick, Brian; Miller, Brian; García-Rizo, Clemente; Fernandez-Egea, Emilio

2015-01-01

The concept of schizophrenia that is most widely taught is that it is a disorder in which psychotic symptoms are the main problem, and a dysregulation of dopamine signaling is the main feature of pathophysiology. However, this concept limits clinical assessment, the treatments offered to patients, research, and the development of therapeutics. A more appropriate conceptual model is that: 1) schizophrenia is not a psychotic disorder, but a disorder of essentially every brain function in which psychosis is present; 2) it is not a brain disease, but a disorder with impairments throughout the body; 3) for many patients, neuropsychiatric problems other than psychosis contribute more to impairment in function and quality of life than does psychosis; and, 4) some conditions that are considered to be comorbid are integral parts of the illness. In conclusion, students, patients, and family members should be taught this model, along with its implications for assessment, research, and therapeutics. PMID:23518782

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

The intestinal microbiome, probiotics and prebiotics in neurogastroenterology

PubMed Central

Saulnier, Delphine M.; Ringel, Yehuda; Heyman, Melvin B.; Foster, Jane A.; Bercik, Premysl; Shulman, Robert J.; Versalovic, James; Verdu, Elena F.; Dinan, Ted G.; Hecht, Gail; Guarner, Francisco

2013-01-01

The brain-gut axis allows bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent experimental work suggests that the gut microbiota have an impact on the brain-gut axis. A group of experts convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) discussed the role of gut bacteria on brain functions and the implications for probiotic and prebiotic science. The experts reviewed and discussed current available data on the role of gut microbiota on epithelial cell function, gastrointestinal motility, visceral sensitivity, perception and behavior. Data, mostly gathered from animal studies, suggest interactions of gut microbiota not only with the enteric nervous system but also with the central nervous system via neural, neuroendocrine, neuroimmune and humoral links. Microbial colonization impacts mammalian brain development in early life and subsequent adult behavior. These findings provide novel insights for improved understanding of the potential role of gut microbial communities on psychological disorders, most particularly in the field of psychological comorbidities associated with functional bowel disorders like irritable bowel syndrome (IBS) and should present new opportunity for interventions with pro- and prebiotics. PMID:23202796

Disrupted topology of hippocampal connectivity is associated with short-term antidepressant response in major depressive disorder.

PubMed

Gong, Liang; Hou, Zhenghua; Wang, Zan; He, Cancan; Yin, Yingying; Yuan, Yonggui; Zhang, Haisan; Lv, Luxian; Zhang, Hongxing; Xie, Chunming; Zhang, Zhijun

2018-01-01

Graph theoretical analyses have identified disrupted functional topological organization across the brain in patients with major depressive disorder (MDD). However, the relationship between brain topology and short-term treatment responses in patients with MDD remains unknown. Sixty-eight patients with MDD and 63 cognitively normal (CN) subjects were recruited at baseline and underwent resting-state functional magnetic resonance imaging scans. Graph theory analysis was used to examine group differences in the whole-brain functional topological properties. The association between altered brain topology and the early antidepressant response was examined. Patients with MDD showed lower normalized clustering coefficients, lower small-worldness scalars and increased nodal efficiencies in the default mode network and decreased nodal efficiencies in basal ganglia and hippocampal networks. In addition, the decreased nodal efficiency in left hippocampus was negatively correlated with depressive severity at baseline and positively correlated with changes in the depressive scores after two weeks of antidepressant treatment. The patients in the present study received different medications. These findings indicated that the altered brain functional topological organization in patients with MDD is associated with the treatment response in the early phase of medication. Therefore, brain topology assessments might be considered a useful and convenient predictor of short-term antidepressant responses. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic and epigenetic factors underlying sex differences in the regulation of gene expression in the brain

PubMed Central

Ratnu, Vikram S.; Emami, Michael R.; Bredy, Timothy W.

2016-01-01

There are inherent biological differences between males and females that contribute to sex differences in brain function and to many sex-specific illnesses and disorders. Traditionally, it has been thought that such differences are largely due to hormonal regulation; however, there are also genetic and epigenetic effects caused by the inheritance and unequal dosage of genes located on the X- and Y-chromosomes. Here we discuss the evidence in favor of a genetic and epigenetic basis for sexually dimorphic behavior, as a consequence of underlying differences in the regulation of genes that drive brain function. A better understanding of sex-specific molecular processes in the brain will provide further insight for the development of novel therapeutic approaches for the treatment of neuropsychiatric disorders characterized by gender/sex differences. PMID:27870402

Abnormal small-world brain functional networks in obsessive-compulsive disorder patients with poor insight.

PubMed

Lei, Hui; Cui, Yan; Fan, Jie; Zhang, Xiaocui; Zhong, Mingtian; Yi, Jinyao; Cai, Lin; Yao, Dezhong; Zhu, Xiongzhao

2017-09-01

There are limited data on neurobiological correlates of poor insight in obsessive-compulsive disorder (OCD). This study explored whether specific changes occur in small-world network (SWN) properties in the brain functional network of OCD patients with poor insight. Resting-state electroencephalograms (EEGs) were recorded for 12 medication-free OCD patients with poor insight, 50 medication-free OCD patients with good insight, and 36 healthy controls. Both of the OCD groups exhibited topological alterations in the brain functional network characterized by abnormal small-world parameters at the beta band. However, the alterations at the theta band only existed in the OCD patients with poor insight. A relatively small sample size. Subjects were naïve to medications and those with Axis I comorbidity were excluded, perhaps limiting generalizability. Disrupted functional integrity at the beta bands of the brain functional network may be related to OCD, while disrupted functional integrity at the theta band may be associated with poor insight in OCD patients, thus this study might provide novel insight into our understanding of the pathophysiology of OCD. Copyright © 2017 Elsevier B.V. All rights reserved.

Cognitive profile and disorders affecting higher brain functions in paediatric patients with neurofibromatosis type 1.

PubMed

Vaucheret Paz, E; López Ballent, A; Puga, C; García Basalo, M J; Baliarda, F; Ekonen, C; Ilari, R; Agosta, G

2017-04-18

Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome often associated with specific cognitive deficits that are rarely monitored during follow-up of these patients. The purpose of our study is two-fold. First, we aimed to describe the cognitive profile of patients with NF1 and detect disorders in higher brain functions associated with the disease. Second, we identified the reasons for consultation associated with school performance in these patients. We conducted a descriptive cross-sectional study of 24 paediatric patients (ages 5 to 16) with NF1 who underwent neuropsychological assessment. The most frequent reasons for consultation were attention deficits (58.33%), learning disorders (25%), poor motor coordination (25%), and language impairment (0.8%). Although 96% of the patients displayed impairments in at least one of the assessed areas, only 83.34% of the parents had reported such impairments. Attention-deficit/hyperactivity disorder was present in 58.33% of the patients, whereas 33.33% had nonverbal learning disabilities, 20.83% had expressive language disorder, 8.33% had borderline intellectual functioning, 4.16% had mental retardation, and only 4.16% showed no cognitive impairment. Higher brain functions are frequently impaired in paediatric patients with NF1. Although many parents report such disorders, they can go undetected in some cases. Neuropsychological assessment is recommended for all paediatric patients with NF1 to detect cognitive impairment and provide early, effective rehabilitation treatment. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The effects of vitamin D on brain development and adult brain function.

PubMed

Kesby, James P; Eyles, Darryl W; Burne, Thomas H J; McGrath, John J

2011-12-05

A role for vitamin D in brain development and function has been gaining support over the last decade. Multiple lines of evidence suggest that this vitamin is actually a neuroactive steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with a host of adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. This review summarises the current state of research on the actions of vitamin D in the brain and the consequences of deficiencies in this vitamin. Furthermore, we discuss specific implications of vitamin D status on the neurotransmitter, dopamine. Copyright © 2011 Elsevier Ltd. All rights reserved.

Multimodal mapping of the brain's functional connectivity and the adult outcome of attention deficit hyperactivity disorder.

PubMed

Sudre, Gustavo; Szekely, Eszter; Sharp, Wendy; Kasparek, Steven; Shaw, Philip

2017-10-31

We have a limited understanding of why many children with attention deficit hyperactivity disorder do not outgrow the disorder by adulthood. Around 20-30% retain the full syndrome as young adults, and about 50% show partial, rather than complete, remission. Here, to delineate the neurobiology of this variable outcome, we ask if the persistence of childhood symptoms into adulthood impacts on the brain's functional connectivity. We studied 205 participants followed clinically since childhood. In early adulthood, participants underwent magnetoencephalography (MEG) to measure neuronal activity directly and functional MRI (fMRI) to measure hemodynamic activity during a task-free period (the "resting state"). We found that symptoms of inattention persisting into adulthood were associated with disrupted patterns of typical functional connectivity in both MEG and fMRI. Specifically, those with persistent inattention lost the typical balance of connections within the default mode network (DMN; prominent during introspective thought) and connections between this network and those supporting attention and cognitive control. By contrast, adults whose childhood inattentive symptoms had resolved did not differ significantly from their never-affected peers, both hemodynamically and electrophysiologically. The anomalies in functional connectivity tied to clinically significant inattention centered on midline regions of the DMN in both MEG and fMRI, boosting confidence in a possible pathophysiological role. The findings suggest that the clinical course of this common childhood onset disorder impacts the functional connectivity of the adult brain. Published under the PNAS license.

Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery.

PubMed

Vazana, Udi; Veksler, Ronel; Pell, Gaby S; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio; Friedman, Alon

2016-07-20

The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. Copyright © 2016 the authors 0270-6474/16/367727-13$15.00/0.

Glutamate-Mediated Blood–Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery

PubMed Central

Vazana, Udi; Veksler, Ronel; Pell, Gaby S.; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio

2016-01-01

The blood–brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood–brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood–brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo. Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood–brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood–brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT In this study, we reveal a new mechanism that governs blood–brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. PMID:27445149

Sugar for the brain: the role of glucose in physiological and pathological brain function

PubMed Central

Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A.; Meisel, Andreas

2013-01-01

The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We aim at synthesizing these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation which lead to disease. PMID:23968694

Fetal alcohol spectrum disorders: an overview.

PubMed

Riley, Edward P; Infante, M Alejandra; Warren, Kenneth R

2011-06-01

When fetal alcohol syndrome (FAS) was initially described, diagnosis was based upon physical parameters including facial anomalies and growth retardation, with evidence of developmental delay or mental deficiency. Forty years of research has shown that FAS lies towards the extreme end of what are now termed fetal alcohol spectrum disorders (FASD). The most profound effects of prenatal alcohol exposure are on the developing brain and the cognitive and behavioral effects that ensue. Alcohol exposure affects brain development via numerous pathways at all stages from neurogenesis to myelination. For example, the same processes that give rise to the facial characteristics of FAS also cause abnormal brain development. Behaviors as diverse as executive functioning to motor control are affected. This special issue of Neuropsychology Review addresses these changes in brain and behavior highlighting the relationship between the two. A diagnostic goal is to recognize FAS as a disorder of brain rather than one of physical characteristics.

Resting-State Functional Connectivity in the Human Connectome Project: Current Status and Relevance to Understanding Psychopathology.

PubMed

Barch, Deanna M

A key tenet of modern psychiatry is that psychiatric disorders arise from abnormalities in brain circuits that support human behavior. Our ability to examine hypotheses around circuit-level abnormalities in psychiatric disorders has been made possible by advances in human neuroimaging technologies. These advances have provided the basis for recent efforts to develop a more complex understanding of the function of brain circuits in health and of their relationship to behavior-providing, in turn, a foundation for our understanding of how disruptions in such circuits contribute to the development of psychiatric disorders. This review focuses on the use of resting-state functional connectivity MRI to assess brain circuits, on the advances generated by the Human Connectome Project, and on how these advances potentially contribute to understanding neural circuit dysfunction in psychopathology. The review gives particular attention to the methods developed by the Human Connectome Project that may be especially relevant to studies of psychopathology; it outlines some of the key findings about what constitutes a brain region; and it highlights new information about the nature and stability of brain circuits. Some of the Human Connectome Project's new findings particularly relevant to psychopathology-about neural circuits and their relationships to behavior-are also presented. The review ends by discussing the extension of Human Connectome Project methods across the lifespan and into manifest illness. Potential treatment implications are also considered.

[Transsexualism: a Brain Disorder that Begins to Known].

PubMed

López Moratalla, Natalia; Calleja Canela, Amparo

2016-01-01

Transsexualism describes the condition when a person's psychological gender differs from his or her biological sex. People with gender identity disorder suffer persistently from this incongruence and they search hormonal and surgical sex reassignment to the desired anatomical sex. This review, from an ethical perspective, intends to give an overview of structural and functional neurobiological correlations of transsexualism and their course under cross-sex hormonal administration. Several studies demonstrate an increased functional connectivity between cortex regions reaffirming psychosocial distress of psychologicalbiological sex incongruity. Such distress can be ascribed to a disharmonic body image due to changes in the functional connectivity of the key components of body representation network. These brain alterations seem to imply a strategic mechanism dissociating bodily emotions from bodily images. For a number of sexually dimorphic brain structures or processes, signs of feminization or masculinization are observable in transsexual individuals, who during hormonal administration seem to partly further adjust to characteristics of the desired sex. These changes allow a reduction of psychosocial distress. However, a model leading to a ″gender affirmation″ does not solve the problem, since brain disorders causing it are not corrected. This is a serious medical ethics issue. Prejudices should be left aside. To know what happens in the brain of transsexuals is a medical need, both to define what is and what is not, and so to choose an adequate treatment, and to decide and guide legal actions.

Cognitive functioning in psychiatric disorders following deep brain stimulation.

PubMed

Bergfeld, Isidoor O; Mantione, Mariska; Hoogendoorn, Mechteld L C; Denys, Damiaan

2013-07-01

Deep brain stimulation (DBS) is routinely used as a treatment for treatment-refractory Parkinson's disease and has recently been proposed for psychiatric disorders such as Tourette syndrome (TS), obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Although cognitive deterioration has repeatedly been shown in patients with Parkinson's disease following DBS, the impact of DBS on cognitive functioning in psychiatric patients has not yet been reviewed. Reviewing the available literature on cognitive functioning following DBS in psychiatric patients. A systematic literature search in PubMed, EMBASE and Web of Science, last updated in September 2012, found 1470 papers. Abstracts were scrutinized and 26 studies examining cognitive functioning of psychiatric patients following DBS were included on basis of predetermined inclusion criteria. Twenty-six studies reported cognitive functioning of 130 psychiatric patients following DBS (37 TS patients, 56 OCD patients, 28 MDD patients, 6 patients with Alzheimer's disease, and 3 patients with other disorders). None of the studies reported substantial cognitive decline following DBS. On the contrary, 13 studies reported cognitive improvement following DBS. Preliminary results suggest that DBS in psychiatric disorders does not lead to cognitive decline. In selected cases cognitive functioning was improved following DBS. However, cognitive improvement cannot be conclusively attributed to DBS since studies are hampered by serious limitations. We discuss the outcomes in light of these limitations and offer suggestions for future work. Copyright © 2013 Elsevier Inc. All rights reserved.

Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis.

PubMed

Sacco, Roberto; Gabriele, Stefano; Persico, Antonio M

2015-11-30

Macrocephaly and brain overgrowth have been associated with autism spectrum disorder. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and statistical significance for both head circumference and total brain volume in autism. Our literature search strategy identified 261 and 391 records, respectively; 27 studies defining percentages of macrocephalic patients and 44 structural brain imaging studies providing total brain volumes for patients and controls were included in our meta-analyses. Head circumference was significantly larger in autistic compared to control individuals, with 822/5225 (15.7%) autistic individuals displaying macrocephaly. Structural brain imaging studies measuring brain volume estimated effect size. The effect size is higher in low functioning autistics compared to high functioning and ASD individuals. Brain overgrowth was recorded in 142/1558 (9.1%) autistic patients. Finally, we found a significant interaction between age and total brain volume, resulting in larger head circumference and brain size during early childhood. Our results provide conclusive effect sizes and prevalence rates for macrocephaly and brain overgrowth in autism, confirm the variation of abnormal brain growth with age, and support the inclusion of this endophenotype in multi-biomarker diagnostic panels for clinical use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Aberrant functional brain connectome in people with antisocial personality disorder

PubMed Central

Tang, Yan; Long, Jun; Wang, Wei; Liao, Jian; Xie, Hua; Zhao, Guihu; Zhang, Hao

2016-01-01

Antisocial personality disorder (ASPD) is characterised by a disregard for social obligations and callous unconcern for the feelings of others. Studies have demonstrated that ASPD is associated with abnormalities in brain regions and aberrant functional connectivity. In this paper, topological organisation was examined in resting-state fMRI data obtained from 32 ASPD patients and 32 non-ASPD controls. The frequency-dependent functional networks were constructed using wavelet-based correlations over 90 brain regions. The topology of the functional networks of ASPD subjects was analysed via graph theoretical analysis. Furthermore, the abnormal functional connectivity was determined with a network-based statistic (NBS) approach. Our results revealed that, compared with the controls, the ASPD patients exhibited altered topological configuration of the functional connectome in the frequency interval of 0.016–0.031 Hz, as indicated by the increased clustering coefficient and decreased betweenness centrality in the medial superior frontal gyrus, precentral gyrus, Rolandic operculum, superior parietal gyrus, angular gyrus, and middle temporal pole. In addition, the ASPD patients showed increased functional connectivity mainly located in the default-mode network. The present study reveals an aberrant topological organisation of the functional brain network in individuals with ASPD. Our findings provide novel insight into the neuropathological mechanisms of ASPD. PMID:27257047

Aberrant functional brain connectome in people with antisocial personality disorder.

PubMed

Tang, Yan; Long, Jun; Wang, Wei; Liao, Jian; Xie, Hua; Zhao, Guihu; Zhang, Hao

2016-06-03

Antisocial personality disorder (ASPD) is characterised by a disregard for social obligations and callous unconcern for the feelings of others. Studies have demonstrated that ASPD is associated with abnormalities in brain regions and aberrant functional connectivity. In this paper, topological organisation was examined in resting-state fMRI data obtained from 32 ASPD patients and 32 non-ASPD controls. The frequency-dependent functional networks were constructed using wavelet-based correlations over 90 brain regions. The topology of the functional networks of ASPD subjects was analysed via graph theoretical analysis. Furthermore, the abnormal functional connectivity was determined with a network-based statistic (NBS) approach. Our results revealed that, compared with the controls, the ASPD patients exhibited altered topological configuration of the functional connectome in the frequency interval of 0.016-0.031 Hz, as indicated by the increased clustering coefficient and decreased betweenness centrality in the medial superior frontal gyrus, precentral gyrus, Rolandic operculum, superior parietal gyrus, angular gyrus, and middle temporal pole. In addition, the ASPD patients showed increased functional connectivity mainly located in the default-mode network. The present study reveals an aberrant topological organisation of the functional brain network in individuals with ASPD. Our findings provide novel insight into the neuropathological mechanisms of ASPD.

Primary Cortical Folding in the Human Newborn: An Early Marker of Later Functional Development

ERIC Educational Resources Information Center

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

2008-01-01

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…

Joint Analysis of Band-Specific Functional Connectivity and Signal Complexity in Autism

ERIC Educational Resources Information Center

Ghanbari, Yasser; Bloy, Luke; Edgar, J. Christopher; Blaskey, Lisa; Verma, Ragini; Roberts, Timothy P. L.

2015-01-01

Examination of resting state brain activity using electrophysiological measures like complexity as well as functional connectivity is of growing interest in the study of autism spectrum disorders (ASD). The present paper jointly examined complexity and connectivity to obtain a more detailed characterization of resting state brain activity in ASD.…

[MRI for brain structure and function in patients with first-episode panic disorder].

PubMed

Zhang, Yan; Duan, Lian; Liao, Mei; Yang, Fan; Liu, Jun; Shan, Baoci; Li, Lingjiang

2011-12-01

To determine the brain function and structure in patinets with first-episode panic disorder (PD). All subjects (24 PD patients and 24 healthy subjects) received MRI scan and emotional counting Stroop task during the functional magnetic resonance imaging. Blood oxygenation level dependent functional magnetic resonance imaging and voxel-based morphometric technology were used to detect the gray matter volume. Compared with the healthy controls, left thalamus, left medial frontal gyrus, left anterior cingulate gyrus, left inferior frontal gyrus, left insula (panic-related words vs. neutral words) lacked activation in PD patients, but the over-activation were found in right brain stem, right occipital lobe/lingual gyrus in PD patients. Compared with the healthy controls, the gray matter volume in the PD patients significantly decreased in the left superior temporal gyrus, right medial frontal gyrus, left medial occipital gyrus, dorsomedial nucleus of left thalamus and right anterior cingulate gyrus. There was no significantly increased gray matter volume in any brain area in PD patients. PD patients have selective attentional bias in processing threatening information due to the depression and weakening of the frontal cingulated gyrus.

Zinc in Gut-Brain Interaction in Autism and Neurological Disorders

PubMed Central

Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M.

2015-01-01

A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life. PMID:25878905

“Immune Gate” of Psychopathology—The Role of Gut Derived Immune Activation in Major Psychiatric Disorders

PubMed Central

Rudzki, Leszek; Szulc, Agata

2018-01-01

Interaction between the gastrointestinal tract (GI) and brain functions has recently become a topic of growing interest in psychiatric research. These multidirectional interactions take place in the so-called gut-brain axis or more precisely, the microbiota-gut-brain axis. The GI tract is the largest immune organ in the human body and is also the largest surface of contact with the external environment. Its functions and permeability are highly influenced by psychological stress, which are often a precipitating factor in the first episode, reoccurrence and/or deterioration of symptoms of psychiatric disorders. In recent literature there is growing evidence that increased intestinal permeability with subsequent immune activation has a major role in the pathophysiology of various psychiatric disorders. Numerous parameters measured in this context seem to be aftermaths of those mechanisms, yet at the same time they may be contributing factors for immune mediated psychopathology. For example, immune activation related to gut-derived bacterial lipopolysaccharides (LPS) or various food antigens and exorphins were reported in major depression, schizophrenia, bipolar disorder, alcoholism and autism. In this review the authors will summarize the evidence and roles of such parameters and their assessment in major psychiatric disorders. PMID:29896124

Zinc in gut-brain interaction in autism and neurological disorders.

PubMed

Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M

2015-01-01

A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life.

Schizophrenia.

PubMed

Kahn, René S; Sommer, Iris E; Murray, Robin M; Meyer-Lindenberg, Andreas; Weinberger, Daniel R; Cannon, Tyrone D; O'Donovan, Michael; Correll, Christoph U; Kane, John M; van Os, Jim; Insel, Thomas R

2015-11-12

Schizophrenia is a chronic psychiatric disorder with a heterogeneous genetic and neurobiological background that influences early brain development, and is expressed as a combination of psychotic symptoms - such as hallucinations, delusions and disorganization - and motivational and cognitive dysfunctions. The mean lifetime prevalence of the disorder is just below 1%, but large regional differences in prevalence rates are evident owing to disparities in urbanicity and patterns of immigration. Although gross brain pathology is not a characteristic of schizophrenia, the disorder involves subtle pathological changes in specific neural cell populations and in cell-cell communication. Schizophrenia, as a cognitive and behavioural disorder, is ultimately about how the brain processes information. Indeed, neuroimaging studies have shown that information processing is functionally abnormal in patients with first-episode and chronic schizophrenia. Although pharmacological treatments for schizophrenia can relieve psychotic symptoms, such drugs generally do not lead to substantial improvements in social, cognitive and occupational functioning. Psychosocial interventions such as cognitive-behavioural therapy, cognitive remediation and supported education and employment have added treatment value, but are inconsistently applied. Given that schizophrenia starts many years before a diagnosis is typically made, the identification of individuals at risk and those in the early phases of the disorder, and the exploration of preventive approaches are crucial.

MRI correlates of general intelligence in neurotypical adults.

PubMed

Malpas, Charles B; Genc, Sila; Saling, Michael M; Velakoulis, Dennis; Desmond, Patricia M; O'Brien, Terence J

2016-02-01

There is growing interest in the neurobiological substrate of general intelligence. Psychometric estimates of general intelligence are reduced in a range of neurological disorders, leading to practical application as sensitive, but non-specific, markers of cerebral disorder. This study examined estimates of general intelligence in neurotypical adults using diffusion tensor imaging and resting-state functional connectivity analysis. General intelligence was related to white matter organisation across multiple brain regions, confirming previous work in older healthy adults. We also found that variation in general intelligence was related to a large functional sub-network involving all cortical lobes of the brain. These findings confirm that individual variance in general intelligence is related to diffusely represented brain networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

The psyche and the gut

PubMed Central

Enck, Paul; Martens, Ute; Klosterhalfen, Sibylle

2007-01-01

Research on gut-brain interactions has increased over the last decade and has brought about a number of new topics beyond "classical" subjects, such as "stress" and "personality", which have dominated the psychosomatic literature on gastrointestinal disorders over the past century. These novel topics include brain imaging of intestinal functions, placebo responses in gastroenterology, learning of gastrointestinal symptoms, quality of life in patients with intestinal complaints, and psychotherapy and familial aggregation of functional intestinal disorders. Currently, these new topics appear with a frequency of 1% to 3% in leading gastroenterological journals, either as data presentation or review papers. Increasing focus underlines the importance of enhancing our understanding on how the psyche and the brain communicate in order to better meet the needs of our patients. PMID:17659685

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.

A biopsychological review of gambling disorder

PubMed Central

Quintero, Gabriel C

2017-01-01

The present review is an overview of previous experimental work on biopsychological aspects of gambling disorder. It includes the topics 1) gambling disorder from the neuroimaging and electroencephalography (EEG) perspective, 2) cognitive, executive functioning, and neuropsychological aspects of gambling disorder, and 3) rodent models of gambling disorder. Penalties and losses in gambling can differ in terms of brain activity. Also, specific patterns of brain activity, brain anatomical traits, EEG responses, and cognitive and executive performance can discriminate pathological gamblers from nonpathological gamblers. Also, pathological gamblers can display dysfunction in such brain areas as the insula, frontal lobe, and orbitofrontal cortex. Pathological gambling is a heterogeneous disorder that can vary depending on the severity of cognition, the style of gambling (strategic or not), the prospect of recovery, proneness to relapse, and proneness to treatment withdrawal. Finally, based on rodent models of gambling, the appropriateness of gambling decision is influenced by the presence of cues, the activity of dopamine receptors, and the activity of some brain areas (infralimbic, prelimbic, or rostral agranular insular cortex). Pathological gamblers differed in terms of frontoparietal brain activation compared to nonpathological gamblers (if winning or losing a game). Pathological gamblers had dysfunctional EEG activity. The severity of gambling was linked to the magnification and content of cognitive distortions. The insula was fundamental in the distortion of cognitions linked to result analysis during gambling activity. PMID:28096672

Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity.

PubMed

Val-Laillet, D; Aarts, E; Weber, B; Ferrari, M; Quaresima, V; Stoeckel, L E; Alonso-Alonso, M; Audette, M; Malbert, C H; Stice, E

2015-01-01

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain-behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies.

Informed Consent Decision-Making in Deep Brain Stimulation.

PubMed

Mandarelli, Gabriele; Moretti, Germana; Pasquini, Massimo; Nicolò, Giuseppe; Ferracuti, Stefano

2018-05-11

Deep brain stimulation (DBS) has proved useful for several movement disorders (Parkinson’s disease, essential tremor, dystonia), in which first and/or second line pharmacological treatments were inefficacious. Initial evidence of DBS efficacy exists for refractory obsessive-compulsive disorder, treatment-resistant major depressive disorder, and impulse control disorders. Ethical concerns have been raised about the use of an invasive surgical approach involving the central nervous system in patients with possible impairment in cognitive functioning and decision-making capacity. Most of the disorders in which DBS has been used might present with alterations in memory, attention, and executive functioning, which may have an impact on the mental capacity to give informed consent to neurosurgery. Depression, anxiety, and compulsivity are also common in DBS candidate disorders, and could also be associated with an impaired capacity to consent to treatment or clinical research. Despite these issues, there is limited empirical knowledge on the decision-making levels of these patients. The possible informed consent issues of DBS will be discussed by focusing on the specific treatable diseases.

How should functional imaging of patients with disorders of consciousness contribute to their clinical rehabilitation needs?

PubMed Central

Laureys, Steven; Giacino, Joseph T.; Schiff, Nicholas D.; Schabus, Manuel; Owen, Adrian M.

2010-01-01

Purpose of review We discuss the problems of evidence-based neurorehabilitation in disorders of consciousness, and recent functional neuroimaging data obtained in the vegetative state and minimally conscious state. Recent findings Published data are insufficient to make recommendations for or against any of the neurorehabilitative treatments in vegetative state and minimally conscious state patients. Electrophysiological and functional imaging studies have been shown to be useful in measuring residual brain function in noncommunicative brain-damaged patients. Despite the fact that such studies could in principle allow an objective quantification of the putative cerebral effect of rehabilitative treatment in the vegetative state and minimally conscious state, they have so far not been used in this context. Summary Without controlled studies and careful patient selection criteria it will not be possible to evaluate the potential of therapeutic interventions in disorders of consciousness. There also is a need to elucidate the neurophysiological effects of such treatments. Integration of multimodal neuroimaging techniques should eventually improve our ability to disentangle differences in outcome on the basis of underlying mechanisms and better guide our therapeutic options in the challenging patient populations encountered following severe acute brain damage. PMID:17102688

The Indispensable Roles of Microglia and Astrocytes during Brain Development

PubMed Central

Reemst, Kitty; Noctor, Stephen C.; Lucassen, Paul J.; Hol, Elly M.

2016-01-01

Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same developmental processes such as neuro-/gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis and synaptic pruning. Due to their important instructive roles in these processes, dysfunction of microglia or astrocytes during brain development could contribute to neurodevelopmental disorders and potentially even late-onset neuropathology. A better understanding of the origin, differentiation process and developmental functions of microglia and astrocytes will help to fully appreciate their role both in the developing as well as in the adult brain, in health and disease. PMID:27877121

From the Bottom-Up: Chemotherapy and Gut-Brain Axis Dysregulation.

PubMed

Bajic, Juliana E; Johnston, Ian N; Howarth, Gordon S; Hutchinson, Mark R

2018-01-01

The central nervous system and gastrointestinal tract form the primary targets of chemotherapy-induced toxicities. Symptoms associated with damage to these regions have been clinically termed chemotherapy-induced cognitive impairment and mucositis. Whilst extensive literature outlines the complex etiology of each pathology, to date neither chemotherapy-induced side-effect has considered the potential impact of one on the pathogenesis of the other disorder. This is surprising considering the close bidirectional relationship shared between each organ; the gut-brain axis. There are complex multiple pathways linking the gut to the brain and vice versa in both normal physiological function and disease. For instance, psychological and social factors influence motility and digestive function, symptom perception, and behaviors associated with illness and pathological outcomes. On the other hand, visceral pain affects central nociception pathways, mood and behavior. Recent interest highlights the influence of functional gut disorders, such as inflammatory bowel diseases and irritable bowel syndrome in the development of central comorbidities. Gut-brain axis dysfunction and microbiota dysbiosis have served as key portals in understanding the potential mechanisms associated with these functional gut disorders and their effects on cognition. In this review we will present the role gut-brain axis dysregulation plays in the chemotherapy setting, highlighting peripheral-to-central immune signaling mechanisms and their contribution to neuroimmunological changes associated with chemotherapy exposure. Here, we hypothesize that dysregulation of the gut-brain axis plays a major role in the intestinal, psychological and neurological complications following chemotherapy. We pay particular attention to evidence surrounding microbiota dysbiosis, the role of intestinal permeability, damage to nerves of the enteric and peripheral nervous systems and vagal and humoral mediated changes.

Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder

PubMed Central

Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

2018-01-01

Background Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. Methods The present event-related functional MRI (fMRI) study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially non-overlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). Results We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. Limitations The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Conclusion Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology. PMID:29252163

Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder.

PubMed

Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

2018-01-01

Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. The present event-related functional MRI (fMRI) study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially nonoverlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology.

The Brain Prize 2014: complex human functions.

PubMed

Grigaityte, Kristina; Iacoboni, Marco

2014-11-01

Giacomo Rizzolatti, Stanislas Dehaene, and Trevor Robbins were recently awarded the 2014 Grete Lundbeck European Brain Research Prize for their 'pioneering research on higher brain mechanisms underpinning such complex human functions as literacy, numeracy, motivated behavior and social cognition, and for their effort to understand cognitive and behavioral disorders'. Why was their work highlighted? Is there anything that links together these seemingly disparate lines of research? Copyright © 2014 Elsevier Ltd. All rights reserved.

Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function.

PubMed

Lenz, Kathryn M; Nelson, Lars H

2018-01-01

Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.

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.

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.

The effects of cognitive-behavioral therapy on intrinsic functional brain networks in adults with attention-deficit/hyperactivity disorder.

PubMed

Wang, Xiaoli; Cao, Qingjiu; Wang, Jinhui; Wu, Zhaomin; Wang, Peng; Sun, Li; Cai, Taisheng; Wang, Yufeng

2016-01-01

Cognitive-behavioral therapy (CBT) is an efficacious psychological treatment for adults with attention-deficit/hyperactivity disorder (ADHD), but the neural processes underlying the benefits of CBT are not well understood. This study aims to unravel psychosocial mechanisms for treatment ADHD by exploring the effects of CBT on functional brain networks. Ten adults with ADHD were enrolled and resting-state functional magnetic resonance imaging scans were acquired before and after a 12-session CBT. Twelve age- and gender-matched healthy controls were also scanned. We constructed whole-brain functional connectivity networks using graph-theory approaches and further computed the changes of regional functional connectivity strength (rFCS) between pre- and post-CBT in ADHD for measuring the effects of CBT. The results showed that rFCS was increased in the fronto-parietal network and cerebellum, the brain regions that were most often affected by medication, in adults with ADHD following CBT. Furthermore, the enhanced functional coupling between bilateral superior parietal gyrus was positively correlated with the improvement of ADHD symptoms following CBT. Together, these findings provide evidence that CBT can selectively modulate the intrinsic network connectivity in the fronto-parietal network and cerebellum and suggest that the CBT may share common brain mechanism with the pharmacology in adults with ADHD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Noninvasive brain stimulation treatments for addiction and major depression

PubMed Central

Dunlop, Katharine; Hanlon, Colleen A.

2016-01-01

Major depressive disorder (MDD) and substance use disorders (SUDs) are prevalent, disabling, and challenging illnesses for which new treatment options are needed, particularly in comorbid cases. Neuroimaging studies of the functional architecture of the brain suggest common neural substrates underlying MDD and SUDs. Intrinsic brain activity is organized into a set of functional networks, of which two are particularly relevant to psychiatry. The salience network (SN) is crucial for cognitive control and response inhibition, and deficits in SN function are implicated across a wide variety of psychiatric disorders, including MDD and SUDs. The ventromedial network (VMN) corresponds to the classic reward circuit, and pathological VMN activity for drug cues/negative stimuli is seen in SUDs/MDD. Noninvasive brain stimulation (NIBS) techniques, including rTMS and tDCS, have been used to enhance cortico–striatal–thalamic activity through the core SN nodes in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and anterior insula. Improvements in both MDD and SUD symptoms ensue, including in comorbid cases, via enhanced cognitive control. Inhibition of the VMN also appears promising in preclinical studies for quenching the pathological incentive salience underlying SUDs and MDD. Evolving techniques may further enhance the efficacy of NIBS for MDD and SUD cases that are unresponsive to conventional treatments. PMID:26849183

The Cerebellum and Premenstrual Dysphoric Disorder

PubMed Central

Rapkin, Andrea J.; Berman, Steven M.; London, Edythe D.

2017-01-01

The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed. PMID:28275721

The Cerebellum and Premenstrual Dysphoric Disorder.

PubMed

Rapkin, Andrea J; Berman, Steven M; London, Edythe D

2014-01-01

The cerebellum constitutes ten percent of brain volume and contains the majority of brain neurons. Although it was historically viewed primarily as processing motoric computations, current evidence supports a more comprehensive role, where cerebro-cerebellar feedback loops also modulate various forms of cognitive and affective processing. Here we present evidence for a role of the cerebellum in premenstrual dysphoric disorder (PMDD), which is characterized by severe negative mood symptoms during the luteal phase of the menstrual cycle. Although a link between menstruation and cyclical dysphoria has long been recognized, neuroscientific investigations of this common disorder have only recently been explored. This article reviews functional and structural brain imaging studies of PMDD and the similar but less well defined condition of premenstrual syndrome (PMS). The most consistent findings are that women with premenstrual dysphoria exhibit greater relative activity than other women in the dorsolateral prefrontal cortex and posterior lobules VI and VII of the neocerebellum. Since both brain areas have been implicated in emotional processing and mood disorders, working memory and executive functions, this greater activity probably represents coactivation within a cerebro-cerebellar feedback loop regulating emotional and cognitive processing. Some of the evidence suggests that increased activity within this circuit may preserve cerebellar structure during aging, and possible mechanisms and implications of this finding are discussed.

Changed Hub and Corresponding Functional Connectivity of Subgenual Anterior Cingulate Cortex in Major Depressive Disorder

PubMed Central

Wu, Huawang; Sun, Hui; Xu, Jinping; Wu, Yan; Wang, Chao; Xiao, Jing; She, Shenglin; Huang, Jianwei; Zou, Wenjin; Peng, Hongjun; Lu, Xiaobing; Huang, Guimao; Jiang, Tianzi; Ning, Yuping; Wang, Jiaojian

2016-01-01

Major depressive disorder (MDD) is one of the most prevalent mental disorders. In the brain, the hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of MDD remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods, we investigated whether alterations of hubs can be detected in MDD. First, we constructed the whole-brain voxel-wise functional networks and calculated a functional connectivity strength (FCS) map in each subject in 34 MDD patients and 34 gender-, age- and education level-matched healthy controls (HCs). Next, the two-sample t-test was applied to compare the FCS maps between HC and MDD patients and identified significant decrease of FCS in subgenual anterior cingulate cortex (sgACC) in MDD patients. Subsequent functional connectivity analyses of sgACC showed disruptions in functional connectivity with posterior insula, middle and inferior temporal gyrus, lingual gyrus and cerebellum in MDD patients. Furthermore, the changed FCS of sgACC and functional connections to sgACC were significantly correlated with the Hamilton Depression Rating Scale (HDRS) scores in MDD patients. The results of the present study revealed the abnormal hub of sgACC and its corresponding disrupted frontal-limbic-visual cognitive-cerebellum functional networks in MDD. These findings may provide a new insight for the diagnosis and treatment of MDD. PMID:28018183

Emotional face processing in pediatric bipolar disorder: evidence for functional impairments in the fusiform gyrus.

PubMed

Perlman, Susan B; Fournier, Jay C; Bebko, Genna; Bertocci, Michele A; Hinze, Amanda K; Bonar, Lisa; Almeida, Jorge R C; Versace, Amelia; Schirda, Claudiu; Travis, Michael; Gill, Mary Kay; Demeter, Christine; Diwadkar, Vaibhav A; Sunshine, Jeffrey L; Holland, Scott K; Kowatch, Robert A; Birmaher, Boris; Axelson, David; Horwitz, Sarah M; Arnold, L Eugene; Fristad, Mary A; Youngstrom, Eric A; Findling, Robert L; Phillips, Mary L

2013-12-01

Pediatric bipolar disorder involves poor social functioning, but the neural mechanisms underlying these deficits are not well understood. Previous neuroimaging studies have found deficits in emotional face processing localized to emotional brain regions. However, few studies have examined dysfunction in other regions of the face processing circuit. This study assessed hypoactivation in key face processing regions of the brain in pediatric bipolar disorder. Youth with a bipolar spectrum diagnosis (n = 20) were matched to a nonbipolar clinical group (n = 20), with similar demographics and comorbid diagnoses, and a healthy control group (n = 20). Youth participated in a functional magnetic resonance imaging (fMRI) scanning which employed a task-irrelevant emotion processing design in which processing of facial emotions was not germane to task performance. Hypoactivation, isolated to the fusiform gyrus, was found when viewing animated, emerging facial expressions of happiness, sadness, fearfulness, and especially anger in pediatric bipolar participants relative to matched clinical and healthy control groups. The results of the study imply that differences exist in visual regions of the brain's face processing system and are not solely isolated to emotional brain regions such as the amygdala. Findings are discussed in relation to facial emotion recognition and fusiform gyrus deficits previously reported in the autism literature. Behavioral interventions targeting attention to facial stimuli might be explored as possible treatments for bipolar disorder in youth. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

The study of autism as a distributed disorder

PubMed Central

Müller, Ralph-Axel

2010-01-01

Past autism research has often been dedicated to tracing the causes of the disorder to a localized neurological abnormality, a single functional network, or a single cognitive-behavioral domain. In this review, I argue that autism is a ‘distributed disorder’ on various levels of study (genetic, neuroanatomical, neurofunctional, behavioral). ‘Localizing’ models are therefore not promising. The large array of potential genetic risk factors suggests that multiple (or all) emerging functional brain networks are affected during early development. This is supported by widespread growth abnormalities throughout the brain. Interactions during development between affected functional networks and atypical experiential effects (associated with atypical behavior) in children with autism further complicate the neurological bases of the disorder, resulting in an ‘exponentially distributed’ profile. Promising approaches to a better characterization of neural endophenotypes in autism are provided by techniques investigating white matter and connectivity, such as MR spectroscopy, diffusion tensor imaging (DTI), and functional connectivity MRI. According to a recent hypothesis, the autistic brain is generally characterized by ‘underconnectivity’. However, not all findings are consistent with this view. The concepts and methodology of functional connectivity need to be refined and results need to be corroborated by anatomical studies (such as DTI tractography) before definitive conclusions can be drawn. PMID:17326118

[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.

The Effects of Video Games on Cognition and Brain Structure: Potential Implications for Neuropsychiatric Disorders.

PubMed

Shams, Tahireh A; Foussias, George; Zawadzki, John A; Marshe, Victoria S; Siddiqui, Ishraq; Müller, Daniel J; Wong, Albert H C

2015-09-01

Video games are now a ubiquitous form of entertainment that has occasionally attracted negative attention. Video games have also been used to test cognitive function, as therapeutic interventions for neuropsychiatric disorders, and to explore mechanisms of experience-dependent structural brain changes. Here, we review current research on video games published from January 2011 to April 2014 with a focus on studies relating to mental health, cognition, and brain imaging. Overall, there is evidence that specific types of video games can alter brain structure or improve certain aspects of cognitive functioning. Video games can also be useful as neuropsychological assessment tools. While research in this area is still at a very early stage, there are interesting results that encourage further work in this field, and hold promise for utilizing this technology as a powerful therapeutic and experimental tool.

[Neuroimaging and the neurobiology of obsessive-compulsive disorder].

PubMed

Schiepek, Günter; Tominschek, Igor; Karch, Susanne; Mulert, Christoph; Pogarell, Oliver

2007-01-01

The following review is focusing on results of functional neuroimaging. After some introductory remarks on the phenomenology, epidemiology, and psychotherapy approaches of obsessive-compulsive disorders (OCD) the most important OCD-related brain regions are presented. Obviously, not only the prominent cortico-striato-thalamo-cortical feedback loops are involved, as functional brain imaging studies tell us, but also other regions as the inferior parietal lobe, the anterior and posterior cingulate gyrus, insula, amygdala, cerebellum, and others. Subclassifications using factor-analysis methods support the hypothesis, that most important subtypes ("washing/contamination fear", "obsessions/checking", "symmetry/ordering", "hoarding") involve different, but partially overlapping brain areas. Stimulation paradigms in fMRI-research are commonly based on symptom provocation by visual or tactile stimuli, or on action-monitoring and error-monitoring tasks. Deficits in action-monitoring and planning are discussed to be one of the basic dysfunctions of OCD. Finally, results of psychotherapeutic induced variations of brain activations in OCD are presented.

[Influence of factors on independence of patients after stroke in early rehabilitation stage].

PubMed

Petruseviciene, Daiva; Krisciūnas, Aleksandras

2005-01-01

Brain stroke is the main cause of disability starting from age of 40 years. Due to this disability, a person loses his ability to work because of long-lasting disorders of biosocial functions. According to literature, occupational therapy for such patients, taking regard to their social, cultural and economic background, significantly increases their self-care and independence and helps to educate working skills. OBJECTIVE. To evaluate conditional disorders of patients with stroke under rehabilitation and to establish the influence of extent of brain damage, localization, age and gender on effectiveness of occupational therapy. Study included 47 men and 53 women diagnosed with brain ischemia or hemorrhage (ischemic or hemorrhagic stroke). Out of them, 30 were of working age (18-59 years old) and 70 of non-working age (more than 60 years old). The mean age was 63.4+/-1.2 years. In order to assess the functional status of patients, they were tested using the Functional Independence Measure (FIM). At the start of rehabilitation, the mean FIM score was 47.4+/-16.1 (48.9+/-15.6 for men and 46.3+/-16.6 for women, p>0.05). At the end of early rehabilitation, the mean FIM score reached up to 89.9+/-22.3 (94.7+/-18.9 for men and 85.7+/-24.3 for women, p<0.05). Evaluation of functional status showed that at the start of rehabilitation functional status was worse in women than men, nevertheless, women's functional status improved during rehabilitation, though the difference between men and women still remained. Occupational therapy was less effective for patients who suffered from hemiplegia than for patients with hemiparesis (p<0.01). Older patients (more than 60 years) had more expressed functional disorders, and worse functional recovery comparing with younger, working age patients (18-59 years old). Evaluation of occupational therapy effectiveness at the end of early rehabilitation showed that extent of brain damage influences independence of patients suffering from brain stroke (p<0.01).

Default mode network, motor network, dorsal and ventral basal ganglia networks in the rat brain: comparison to human networks using resting state-fMRI.

PubMed

Sierakowiak, Adam; Monnot, Cyril; Aski, Sahar Nikkhou; Uppman, Martin; Li, Tie-Qiang; Damberg, Peter; Brené, Stefan

2015-01-01

Rodent models are developed to enhance understanding of the underlying biology of different brain disorders. However, before interpreting findings from animal models in a translational aspect to understand human disease, a fundamental step is to first have knowledge of similarities and differences of the biological systems studied. In this study, we analyzed and verified four known networks termed: default mode network, motor network, dorsal basal ganglia network, and ventral basal ganglia network using resting state functional MRI (rsfMRI) in humans and rats. Our work supports the notion that humans and rats have common robust resting state brain networks and that rsfMRI can be used as a translational tool when validating animal models of brain disorders. In the future, rsfMRI may be used, in addition to short-term interventions, to characterize longitudinal effects on functional brain networks after long-term intervention in humans and rats.

Default Mode Network, Motor Network, Dorsal and Ventral Basal Ganglia Networks in the Rat Brain: Comparison to Human Networks Using Resting State-fMRI

PubMed Central

Sierakowiak, Adam; Monnot, Cyril; Aski, Sahar Nikkhou; Uppman, Martin; Li, Tie-Qiang; Damberg, Peter; Brené, Stefan

2015-01-01

Rodent models are developed to enhance understanding of the underlying biology of different brain disorders. However, before interpreting findings from animal models in a translational aspect to understand human disease, a fundamental step is to first have knowledge of similarities and differences of the biological systems studied. In this study, we analyzed and verified four known networks termed: default mode network, motor network, dorsal basal ganglia network, and ventral basal ganglia network using resting state functional MRI (rsfMRI) in humans and rats. Our work supports the notion that humans and rats have common robust resting state brain networks and that rsfMRI can be used as a translational tool when validating animal models of brain disorders. In the future, rsfMRI may be used, in addition to short-term interventions, to characterize longitudinal effects on functional brain networks after long-term intervention in humans and rats. PMID:25789862

Developmental programming of brain and behavior by perinatal diet: focus on inflammatory mechanisms

PubMed Central

Bolton, Jessica L.; Bilbo, Staci D.

2014-01-01

Obesity is now epidemic worldwide. Beyond associated diseases such as diabetes, obesity is linked to neuropsychiatric disorders such as depression. Alarmingly maternal obesity and high-fat diet consumption during gestation/lactation may “program” offspring longterm for increased obesity themselves, along with increased vulnerability to mood disorders. We review the evidence that programming of brain and behavior by perinatal diet is propagated by inflammatory mechanisms, as obesity and high-fat diets are independently associated with exaggerated systemic levels of inflammatory mediators. Due to the recognized dual role of these immune molecules (eg, interleukin [IL]-6, 11-1β) in placental function and brain development, any disruption of their delicate balance with growth factors or neurotransmitters (eg, serotonin) by inflammation early in life can permanently alter the trajectory of fetal brain development. Finally, epigenetic regulation of inflammatory pathways is a likely candidate for persistent changes in metabolic and brain function as a consequence of the perinatal environment. PMID:25364282

The implications of brain connectivity in the neuropsychology of autism

PubMed Central

Maximo, Jose O.; Cadena, Elyse J.; Kana, Rajesh K.

2014-01-01

Autism is a neurodevelopmental disorder that has been associated with atypical brain functioning. Functional connectivity MRI (fcMRI) studies examining neural networks in autism have seen an exponential rise over the last decade. Such investigations have led to characterization of autism as a distributed neural systems disorder. Studies have found widespread cortical underconnectivity, local overconnectivity, and mixed results suggesting disrupted brain connectivity as a potential neural signature of autism. In this review, we summarize the findings of previous fcMRI studies in autism with a detailed examination of their methodology, in order to better understand its potential and to delineate the pitfalls. We also address how a multimodal neuroimaging approach (incorporating different measures of brain connectivity) may help characterize the complex neurobiology of autism at a global level. Finally, we also address the potential of neuroimaging-based markers in assisting neuropsychological assessment of autism. The quest for a biomarker for autism is still ongoing, yet new findings suggest that aberrant brain connectivity may be a promising candidate. PMID:24496901

New developments in brain research of internet and gaming disorder.

PubMed

Weinstein, Aviv; Livny, Abigail; Weizman, Abraham

2017-04-01

There is evidence that the neural mechanisms underlying Internet Gaming Disorder (IGD) resemble those of drug addiction. Functional Magnetic Resonance Imaging (fMRI) studies of the resting state and measures of gray matter volume have shown that Internet game playing was associated with changes to brain regions responsible for attention and control, impulse control, motor function, emotional regulation, sensory-motor coordination. Furthermore, Internet game playing was associated with lower white matter density in brain regions that are involved in decision-making, behavioral inhibition and emotional regulation. Videogame playing involved changes in reward inhibitory mechanisms and loss of control. Structural brain imaging studies showed alterations in the volume of the ventral striatum that is an important part of the brain's reward mechanisms. Finally, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and lower dopamine transporter and dopamine receptor D 2 occupancy indicating sub-sensitivity of dopamine reward mechanisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Temporal Lobe and “Default” Hemodynamic Brain Modes Discriminate Between Schizophrenia and Bipolar Disorder

PubMed Central

Calhoun, Vince D.; Maciejewski, Paul K.; Pearlson, Godfrey D.; Kiehl, Kent A.

2009-01-01

Schizophrenia and bipolar disorder are currently diagnosed on the basis of psychiatric symptoms and longitudinal course. The determination of a reliable, biologically-based diagnostic indicator of these diseases (a biomarker) could provide the groundwork for developing more rigorous tools for differential diagnosis and treatment assignment. Recently, methods have been used to identify distinct sets of brain regions or “spatial modes” exhibiting temporally coherent brain activity. Using functional magnetic resonance imaging (fMRI) data and a multivariate analysis method, independent component analysis, we combined the temporal lobe and the default modes to discriminate subjects with bipolar disorder, chronic schizophrenia, and healthy controls. Temporal lobe and default mode networks were reliably identified in all participants. Classification results on an independent set of individuals revealed an average sensitivity and specificity of 90 and 95%, respectively. The use of coherent brain networks such as the temporal lobe and default mode networks may provide a more reliable measure of disease state than task-correlated fMRI activity. A combination of two such hemodynamic brain networks shows promise as a biomarker for schizophrenia and bipolar disorder. PMID:17894392

Temporal lobe and "default" hemodynamic brain modes discriminate between schizophrenia and bipolar disorder.

PubMed

Calhoun, Vince D; Maciejewski, Paul K; Pearlson, Godfrey D; Kiehl, Kent A

2008-11-01

Schizophrenia and bipolar disorder are currently diagnosed on the basis of psychiatric symptoms and longitudinal course. The determination of a reliable, biologically-based diagnostic indicator of these diseases (a biomarker) could provide the groundwork for developing more rigorous tools for differential diagnosis and treatment assignment. Recently, methods have been used to identify distinct sets of brain regions or "spatial modes" exhibiting temporally coherent brain activity. Using functional magnetic resonance imaging (fMRI) data and a multivariate analysis method, independent component analysis, we combined the temporal lobe and the default modes to discriminate subjects with bipolar disorder, chronic schizophrenia, and healthy controls. Temporal lobe and default mode networks were reliably identified in all participants. Classification results on an independent set of individuals revealed an average sensitivity and specificity of 90 and 95%, respectively. The use of coherent brain networks such as the temporal lobe and default mode networks may provide a more reliable measure of disease state than task-correlated fMRI activity. A combination of two such hemodynamic brain networks shows promise as a biomarker for schizophrenia and bipolar disorder.

A Systems Neuroscience Approach to the Pathophysiology of Pediatric Mood and Anxiety Disorders

PubMed Central

Leibenluft, Ellen; Brotman, Melissa A.

2015-01-01

Emotional dysregulation is a core feature of pediatric mood and anxiety disorders. Emerging evidence suggests that these disorders are mediated by abnormalities in the functions and structures of the developing brain. This chapter reviews recent behavioral and functional magnetic resonance imaging (fMRI) research on pediatric mood and anxiety disorders, focusing on the neural mechanisms underlying these disorders. Throughout the chapter, we highlight the relationship between neural and behavioral findings, and potential novel treatments. The chapter concludes with directions for future research. PMID:24281907

De novo mutations in regulatory elements in neurodevelopmental disorders

PubMed Central

Short, Patrick J.; McRae, Jeremy F.; Gallone, Giuseppe; Sifrim, Alejandro; Won, Hyejung; Geschwind, Daniel H.; Wright, Caroline F.; Firth, Helen V; FitzPatrick, David R.; Barrett, Jeffrey C.; Hurles, Matthew E.

2018-01-01

We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders. PMID:29562236

Comparative study of nonlinear properties of EEG signals of normal persons and epileptic patients

PubMed Central

2009-01-01

Background Investigation of the functioning of the brain in living systems has been a major effort amongst scientists and medical practitioners. Amongst the various disorder of the brain, epilepsy has drawn the most attention because this disorder can affect the quality of life of a person. In this paper we have reinvestigated the EEGs for normal and epileptic patients using surrogate analysis, probability distribution function and Hurst exponent. Results Using random shuffled surrogate analysis, we have obtained some of the nonlinear features that was obtained by Andrzejak et al. [Phys Rev E 2001, 64:061907], for the epileptic patients during seizure. Probability distribution function shows that the activity of an epileptic brain is nongaussian in nature. Hurst exponent has been shown to be useful to characterize a normal and an epileptic brain and it shows that the epileptic brain is long term anticorrelated whereas, the normal brain is more or less stochastic. Among all the techniques, used here, Hurst exponent is found very useful for characterization different cases. Conclusion In this article, differences in characteristics for normal subjects with eyes open and closed, epileptic subjects during seizure and seizure free intervals have been shown mainly using Hurst exponent. The H shows that the brain activity of a normal man is uncorrelated in nature whereas, epileptic brain activity shows long range anticorrelation. PMID:19619290

Treatment-resistant panic disorder: clinical significance, concept and management.

PubMed

Chen, Mu-Hong; Tsai, Shih-Jen

2016-10-03

Panic disorder is commonly prevalent in the population, but the treatment response for panic disorder in clinical practice is much less effective than that in our imagination. Increasing evidence suggested existence of a chronic or remitting-relapsing clinical course in panic disorder. In this systematic review, we re-examine the definition of treatment-resistant panic disorder, and present the potential risk factors related to the treatment resistance, including the characteristics of panic disorder, other psychiatric and physical comorbidities, and psychosocial stresses. Furthermore, we summarize the potential pathophysiologies, such as genetic susceptibility, altered brain functioning, brain-derived neurotrophic factor, and long-term inflammation, to explain the treatment resistance. Finally, we conclude the current therapeutic strategies for treating treatment-resistant panic disorder from pharmacological and non-pharmacological views. Copyright © 2016 Elsevier Inc. All rights reserved.

Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy

PubMed Central

Shamseldin, Hanan E.; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S.; Gleeson, Joseph G.; Alkuraya, Fowzan S.

2016-01-01

Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. PMID:26708753

Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease.

PubMed

Wang, Liqun; Xia, Jing; Li, Jonathan; Hagemann, Tracy L; Jones, Jeffrey R; Fraenkel, Ernest; Weitz, David A; Zhang, Su-Chun; Messing, Albee; Feany, Mel B

2018-05-15

Glial cells have increasingly been implicated as active participants in the pathogenesis of neurological diseases, but critical pathways and mechanisms controlling glial function and secondary non-cell autonomous neuronal injury remain incompletely defined. Here we use models of Alexander disease, a severe brain disorder caused by gain-of-function mutations in GFAP, to demonstrate that misregulation of GFAP leads to activation of a mechanosensitive signaling cascade characterized by activation of the Hippo pathway and consequent increased expression of A-type lamin. Importantly, we use genetics to verify a functional role for dysregulated mechanotransduction signaling in promoting behavioral abnormalities and non-cell autonomous neurodegeneration. Further, we take cell biological and biophysical approaches to suggest that brain tissue stiffness is increased in Alexander disease. Our findings implicate altered mechanotransduction signaling as a key pathological cascade driving neuronal dysfunction and neurodegeneration in Alexander disease, and possibly also in other brain disorders characterized by gliosis.

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.

Using human brain imaging studies as a guide towards animal models of schizophrenia

PubMed Central

BOLKAN, Scott S.; DE CARVALHO, Fernanda D.; KELLENDONK, Christoph

2015-01-01

Schizophrenia is a heterogeneous and poorly understood mental disorder that is presently defined solely by its behavioral symptoms. Advances in genetic, epidemiological and brain imaging techniques in the past half century, however, have significantly advanced our understanding of the underlying biology of the disorder. In spite of these advances clinical research remains limited in its power to establish the causal relationships that link etiology with pathophysiology and symptoms. In this context, animal models provide an important tool for causally testing hypotheses about biological processes postulated to be disrupted in the disorder. While animal models can exploit a variety of entry points towards the study of schizophrenia, here we describe an approach that seeks to closely approximate functional alterations observed with brain imaging techniques in patients. By modeling these intermediate pathophysiological alterations in animals, this approach offers an opportunity to (1) tightly link a single functional brain abnormality with its behavioral consequences, and (2) to determine whether a single pathophysiology can causally produce alterations in other brain areas that have been described in patients. In this review we first summarize a selection of well-replicated biological abnormalities described in the schizophrenia literature. We then provide examples of animal models that were studied in the context of patient imaging findings describing enhanced striatal dopamine D2 receptor function, alterations in thalamo-prefrontal circuit function, and metabolic hyperfunction of the hippocampus. Lastly, we discuss the implications of findings from these animal models for our present understanding of schizophrenia, and consider key unanswered questions for future research in animal models and human patients. PMID:26037801

Overlap between functional GI disorders and other functional syndromes: what are the underlying mechanisms?

PubMed Central

KIM, S. E.; CHANG, L.

2013-01-01

Background Irritable bowel syndrome and other gastrointestinal (GI) and non-GI disorders such as functional dyspepsia, fibromyalgia, temporomandibular joint disorder, interstitial cystitis/painful bladder syndrome, and chronic fatigue syndrome are known as functional pain syndromes. They commonly coexist within the same individual. The pathophysiologic mechanisms of these disorders are not well understood, but it has been hypothesized that they share a common pathogenesis. Purpose The objective of this review is to discuss the proposed pathophysiologic mechanisms, which have been similarly studied in these conditions. These mechanisms include enhanced pain perception, altered regional brain activation, infectious etiologies, dysregulations in immune and neuroendocrine function, and genetic susceptibility. Studies suggest that these functional disorders are multifactorial, but factors which increase the vulnerability of developing these conditions are shared. PMID:22863120

Sugar for the brain: the role of glucose in physiological and pathological brain function.

PubMed

Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A; Meisel, Andreas

2013-10-01

The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 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.

Identifying dynamic functional connectivity biomarkers using GIG-ICA: Application to schizophrenia, schizoaffective disorder, and psychotic bipolar disorder.

PubMed

Du, Yuhui; Pearlson, Godfrey D; Lin, Dongdong; Sui, Jing; Chen, Jiayu; Salman, Mustafa; Tamminga, Carol A; Ivleva, Elena I; Sweeney, John A; Keshavan, Matcheri S; Clementz, Brett A; Bustillo, Juan; Calhoun, Vince D

2017-05-01

Functional magnetic resonance imaging (fMRI) studies have shown altered brain dynamic functional connectivity (DFC) in mental disorders. Here, we aim to explore DFC across a spectrum of symptomatically-related disorders including bipolar disorder with psychosis (BPP), schizoaffective disorder (SAD), and schizophrenia (SZ). We introduce a group information guided independent component analysis procedure to estimate both group-level and subject-specific connectivity states from DFC. Using resting-state fMRI data of 238 healthy controls (HCs), 140 BPP, 132 SAD, and 113 SZ patients, we identified measures differentiating groups from the whole-brain DFC and traditional static functional connectivity (SFC), separately. Results show that DFC provided more informative measures than SFC. Diagnosis-related connectivity states were evident using DFC analysis. For the dominant state consistent across groups, we found 22 instances of hypoconnectivity (with decreasing trends from HC to BPP to SAD to SZ) mainly involving post-central, frontal, and cerebellar cortices as well as 34 examples of hyperconnectivity (with increasing trends HC through SZ) primarily involving thalamus and temporal cortices. Hypoconnectivities/hyperconnectivities also showed negative/positive correlations, respectively, with clinical symptom scores. Specifically, hypoconnectivities linking postcentral and frontal gyri were significantly negatively correlated with the PANSS positive/negative scores. For frontal connectivities, BPP resembled HC while SAD and SZ were more similar. Three connectivities involving the left cerebellar crus differentiated SZ from other groups and one connection linking frontal and fusiform cortices showed a SAD-unique change. In summary, our method is promising for assessing DFC and may yield imaging biomarkers for quantifying the dimension of psychosis. Hum Brain Mapp 38:2683-2708, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Self-regulation of brain oscillations as a treatment for aberrant brain connections in children with autism.

PubMed

Pineda, J A; Juavinett, A; Datko, M

2012-12-01

Autism is a highly varied developmental disorder typically characterized by deficits in reciprocal social interaction, difficulties with verbal and nonverbal communication, and restricted interests and repetitive behaviors. Although a wide range of behavioral, pharmacological, and alternative medicine strategies have been reported to ameliorate specific symptoms for some individuals, there is at present no cure for the condition. Nonetheless, among the many incompatible observations about aspects of the development, anatomy, and functionality of the autistic brain, it is widely agreed that it is characterized by widespread aberrant connectivity. Such disordered connectivity, be it increased, decreased, or otherwise compromised, may complicate healthy synchronization and communication among and within different neural circuits, thereby producing abnormal processing of sensory inputs necessary for normal social life. It is widely accepted that the innate properties of brain electrical activity produce pacemaker elements and linked networks that oscillate synchronously or asynchronously, likely reflecting a type of functional connectivity. Using phase coherence in multiple frequency EEG bands as a measure of functional connectivity, studies have shown evidence for both global hypoconnectivity and local hyperconnectivity in individuals with ASD. However, the nature of the brain's experience-dependent structural plasticity suggests that these abnormal patterns may be reversed with the proper type of treatment. Indeed, neurofeedback (NF) training, an intervention based on operant conditioning that results in self-regulation of brain electrical oscillations, has shown promise in addressing marked abnormalities in functional and structural connectivity. It is hypothesized that neurofeedback produces positive behavioral changes in ASD children by normalizing the aberrant connections within and between neural circuits. NF exploits the brain's plasticity to normalize aberrant connectivity patterns apparent in the autistic brain. By grounding this training in known anatomical (e.g., mirror neuron system) and functional markers (e.g., mu rhythms) of autism, NF training holds promise to support current treatments for this complex disorder. The proposed hypothesis specifically states that neurofeedback-induced alpha mu (8-12Hz) rhythm suppression or desynchronization, a marker of cortical activation, should induce neuroplastic changes and lead to normalization in relevant mirroring networks that have been associated with higher-order social cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.

Motor-Perceptual Function in Children with Developmental Reading Disorders: Neuropsychophysiological Analysis.

ERIC Educational Resources Information Center

Chiarenza, Giuseppe Augusto

1990-01-01

Eight reading-disordered and 9 nondisabled males (age 10) performed a skilled motor-perceptual task. The children with reading disorders were slower, less accurate, and achieved a smaller number of target performances. Their brain macropotentials associated with motor programing, processing of sensory information, and evaluation of the results…

Prefrontal Dysfunction in Attention-Deficit/Hyperactivity Disorder as Measured by Near-Infrared Spectroscopy

ERIC Educational Resources Information Center

Negoro, Hideki; Sawada, Masayuki; Iida, Junzo; Ota, Toyosaku; Tanaka, Shohei; Kishimoto, Toshifumi

2010-01-01

Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders with measurement of hemoglobin concentrations as cerebral blood volume. Twenty medication-naive children with attention-deficit/hyperactivity disorder (ADHD) and 20 age- and sex-matched healthy control…

Resting-state networks link invasive and noninvasive brain stimulation across diverse psychiatric and neurological diseases

PubMed Central

Fox, Michael D.; Buckner, Randy L.; Liu, Hesheng; Chakravarty, M. Mallar; Lozano, Andres M.; Pascual-Leone, Alvaro

2014-01-01

Brain stimulation, a therapy increasingly used for neurological and psychiatric disease, traditionally is divided into invasive approaches, such as deep brain stimulation (DBS), and noninvasive approaches, such as transcranial magnetic stimulation. The relationship between these approaches is unknown, therapeutic mechanisms remain unclear, and the ideal stimulation site for a given technique is often ambiguous, limiting optimization of the stimulation and its application in further disorders. In this article, we identify diseases treated with both types of stimulation, list the stimulation sites thought to be most effective in each disease, and test the hypothesis that these sites are different nodes within the same brain network as defined by resting-state functional-connectivity MRI. Sites where DBS was effective were functionally connected to sites where noninvasive brain stimulation was effective across diseases including depression, Parkinson's disease, obsessive-compulsive disorder, essential tremor, addiction, pain, minimally conscious states, and Alzheimer’s disease. A lack of functional connectivity identified sites where stimulation was ineffective, and the sign of the correlation related to whether excitatory or inhibitory noninvasive stimulation was found clinically effective. These results suggest that resting-state functional connectivity may be useful for translating therapy between stimulation modalities, optimizing treatment, and identifying new stimulation targets. More broadly, this work supports a network perspective toward understanding and treating neuropsychiatric disease, highlighting the therapeutic potential of targeted brain network modulation. PMID:25267639

Reward-Related Brain Function as a Predictor of Treatment Response in Adolescents with Major Depressive Disorder

PubMed Central

Forbes, Erika E.; Olino, Thomas M.; Ryan, Neal D.; Birmaher, Boris; Axelson, David; Moyles, Donna L.; Dahl, Ronald E.

2009-01-01

The current study provides preliminary evidence that pre-treatment reward-related brain function in the striatum and medial prefrontal cortex (PFC) could have relevance for predicting both final level and rate of change of clinical characteristics in adolescents with major depressive disorder. Adolescents with depression underwent a functional MRI scan during a monetary reward task, participated in an 8-week open trial of cognitive behavioral therapy (CBT) or CBT plus selective serotonin reuptake inhibitor, and completed reports of anxiety and depressive symptoms before, during, and after treatment. Clinicians rated adolescents' improvement and severity at the same time points. Growth models were used to examine change in clinical characteristics and its association with brain function. Severity, anxiety symptoms, and depressive symptoms decreased over treatment. Final levels of severity and anxiety symptoms were associated with pre-treatment striatal reactivity, and rate of anxiety symptom reduction was associated with greater striatal reactivity and lower medial PFC reactivity. PMID:20233959

Grey matter abnormalities in children and adolescents with functional neurological symptom disorder.

PubMed

Kozlowska, Kasia; Griffiths, Kristi R; Foster, Sheryl L; Linton, James; Williams, Leanne M; Korgaonkar, Mayuresh S

2017-01-01

Functional neurological symptom disorder refers to the presence of neurological symptoms not explained by neurological disease. Although this disorder is presumed to reflect abnormal function of the brain, recent studies in adults show neuroanatomical abnormalities in brain structure . These structural brain abnormalities have been presumed to reflect long-term adaptations to the disorder, and it is unknown whether child and adolescent patients, with illness that is typically of shorter duration, show similar deficits or have normal brain structure. High-resolution, three-dimensional T1-weighted magnetic resonance images (MRIs) were acquired in 25 patients (aged 10-18 years) and 24 healthy controls. Structure was quantified in terms of grey matter volume using voxel-based morphometry. Post hoc, we examined whether regions of structural difference related to a measure of motor readiness to emotional signals and to clinical measures of illness duration, illness severity, and anxiety/depression. Patients showed greater volumes in the left supplementary motor area (SMA) and right superior temporal gyrus (STG) and dorsomedial prefrontal cortex (DMPFC) (corrected p < 0.05). Previous studies of adult patients have also reported alterations of the SMA. Greater SMA volumes correlated with faster reaction times in identifying emotions but not with clinical measures. The SMA, STG, and DMPFC are known to be involved in the perception of emotion and the modulation of motor responses. These larger volumes may reflect the early expression of an experience-dependent plasticity process associated with increased vigilance to others' emotional states and enhanced motor readiness to organize self-protectively in the context of the long-standing relational stress that is characteristic of this disorder.

The DoD Civilian Equal Employment Opportunity (EEO) Program

DTIC Science & Technology

1987-05-21

as mental retardation, organic brain syndrome , emotional or mental illness, and specific learning disabilities. b. Major Life Activities. Functions...mental or psychological disorder, such as mental retardation, organic brain syndrome , emotional or mental illness, and specific learning disabilities

A Review of Sleep and Its Disorders in Patients with Parkinson's Disease in Relation to Various Brain Structures

PubMed Central

French, Isobel T.; Muthusamy, Kalai A.

2016-01-01

Sleep is an indispensable normal physiology of the human body fundamental for healthy functioning. It has been observed that Parkinson's disease (PD) not only exhibits motor symptoms, but also non-motor symptoms such as metabolic irregularities, altered olfaction, cardiovascular dysfunction, gastrointestinal complications and especially sleep disorders which is the focus of this review. A good understanding and knowledge of the different brain structures involved and how they function in the development of sleep disorders should be well comprehended in order to treat and alleviate these symptoms and enhance quality of life for PD patients. Therefore it is vital that the normal functioning of the body in relation to sleep is well understood before proceeding on to the pathophysiology of PD correlating to its symptoms. Suitable treatment can then be administered toward enhancing the quality of life of these patients, perhaps even discovering the cause for this disease. PMID:27242523

Forniceal deep brain stimulation induces gene expression and splicing changes that promote neurogenesis and plasticity

PubMed Central

Pohodich, Amy E; Yalamanchili, Hari; Raman, Ayush T; Wan, Ying-Wooi; Gundry, Michael; Hao, Shuang; Jin, Haijing; Tang, Jianrong; Liu, Zhandong

2018-01-01

Clinical trials are currently underway to assess the efficacy of forniceal deep brain stimulation (DBS) for improvement of memory in Alzheimer’s patients, and forniceal DBS has been shown to improve learning and memory in a mouse model of Rett syndrome (RTT), an intellectual disability disorder caused by loss-of-function mutations in MECP2. The mechanism of DBS benefits has been elusive, however, so we assessed changes in gene expression, splice isoforms, DNA methylation, and proteome following acute forniceal DBS in wild-type mice and mice lacking Mecp2. We found that DBS upregulates genes involved in synaptic function, cell survival, and neurogenesis and normalized expression of ~25% of the genes altered in Mecp2-null mice. Moreover, DBS induced expression of 17–24% of the genes downregulated in other intellectual disability mouse models and in post-mortem human brain tissue from patients with Major Depressive Disorder, suggesting forniceal DBS could benefit individuals with a variety of neuropsychiatric disorders. PMID:29570050

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training

PubMed Central

Sherwood, Matthew S.; Diller, Emily E.; Ey, Elizabeth; Ganapathy, Subhashini; Nelson, Jeremy T.; Parker, Jason G.

2017-01-01

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can be performed outside of the scanner without the aid of medical professionals or sophisticated medical equipment. In fMRI NFT, the fMRI signal is measured from specific regions of the brain, processed, and presented to the participant in real-time. Through training, self-directed mental processing techniques, that regulate this signal and its underlying neurophysiologic correlates, are developed. FMRI NFT has been used to train volitional control over a wide range of brain regions with implications for several different cognitive, behavioral, and motor systems. Additionally, fMRI NFT has shown promise in a broad range of applications such as the treatment of neurologic disorders and the augmentation of baseline human performance. In this article, we present an fMRI NFT protocol developed at our institution for modulation of both healthy and abnormal brain function, as well as examples of using the method to target both cognitive and auditory regions of the brain. PMID:28872110

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training.

PubMed

Sherwood, Matthew S; Diller, Emily E; Ey, Elizabeth; Ganapathy, Subhashini; Nelson, Jeremy T; Parker, Jason G

2017-08-24

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can be performed outside of the scanner without the aid of medical professionals or sophisticated medical equipment. In fMRI NFT, the fMRI signal is measured from specific regions of the brain, processed, and presented to the participant in real-time. Through training, self-directed mental processing techniques, that regulate this signal and its underlying neurophysiologic correlates, are developed. FMRI NFT has been used to train volitional control over a wide range of brain regions with implications for several different cognitive, behavioral, and motor systems. Additionally, fMRI NFT has shown promise in a broad range of applications such as the treatment of neurologic disorders and the augmentation of baseline human performance. In this article, we present an fMRI NFT protocol developed at our institution for modulation of both healthy and abnormal brain function, as well as examples of using the method to target both cognitive and auditory regions of the brain.

Offspring neuroimmune consequences of maternal malnutrition: Potential mechanism for behavioral impairments that underlie metabolic and neurodevelopmental disorders.

PubMed

Smith, B L; Reyes, T M

2017-10-01

Maternal malnutrition significantly increases offspring risk for both metabolic and neurodevelopmental disorders. Animal models of maternal malnutrition have identified behavioral changes in the adult offspring related to executive function and reward processing. Together, these changes in executive and reward-based behaviors likely contribute to the etiology of both metabolic and neurodevelopmental disorders associated with maternal malnutrition. Concomitant with the behavioral effects, maternal malnutrition alters offspring expression of reward-related molecules and inflammatory signals in brain pathways that control executive function and reward. Neuroimmune pathways and microglial interactions in these specific brain circuits, either in early development or later in adulthood, could directly contribute to the maternal malnutrition-induced behavioral phenotypes. Understanding these mechanisms will help advance treatment strategies for metabolic and neurodevelopmental disorders, especially noninvasive dietary supplementation interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

MYELIN, COPPER, AND THE CUPRIZONE MODEL OF SCHIZOPHRENIA

PubMed Central

Herring, Nicole R.; Konradi, Christine

2010-01-01

In recent years increasing evidence is pointing toward white matter abnormalities in schizophrenia and other psychiatric disorders. The present paper will provide an overview over the role of myelin in cognition and brain function, and its potential involvement in brain disorders. Furthermore, we will examine one particular experimental model for the study of dysmyelination, created by the administration of the toxin cuprizone. Cuprizone, a copper chelator, causes white matter abnormalities in rodents. The administration of cuprizone during specific developmental periods allows for the targeting of specific brain areas for dysmyelination. Thus, cuprizone can be used to study the pathogenesis and pathophysiology of myelin deficiencies in the central nervous system, and its effect on behaviors relevant to psychiatric disorders. PMID:21196354

Intrinsic brain connectivity predicts impulse control disorders in patients with Parkinson's disease.

PubMed

Tessitore, Alessandro; De Micco, Rosa; Giordano, Alfonso; di Nardo, Federica; Caiazzo, Giuseppina; Siciliano, Mattia; De Stefano, Manuela; Russo, Antonio; Esposito, Fabrizio; Tedeschi, Gioacchino

2017-12-01

Impulse control disorders can be triggered by dopamine replacement therapies in patients with PD. Using resting-state functional MRI, we investigated the intrinsic brain network connectivity at baseline in a cohort of drug-naive PD patients who successively developed impulse control disorders over a 36-month follow-up period compared with patients who did not. Baseline 3-Tesla MRI images of 30 drug-naive PD patients and 20 matched healthy controls were analyzed. The impulse control disorders' presence and severity at follow-up were assessed by the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale. Single-subject and group-level independent component analysis was used to investigate functional connectivity differences within the major resting-state networks. We also compared internetwork connectivity between patients. Finally, a multivariate Cox regression model was used to investigate baseline predictors of impulse control disorder development. At baseline, decreased connectivity in the default-mode and right central executive networks and increased connectivity in the salience network were detected in PD patients with impulse control disorders at follow-up compared with those without. Increased default-mode/central executive internetwork connectivity was significantly associated with impulse control disorders development (P < 0.05). Our findings demonstrated that abnormal brain connectivity in the three large-scale networks characterizes drug-naive PD patients who will eventually develop impulse control disorders while on dopaminergic treatment. We hypothesize that these divergent cognitive and limbic network connectivity changes could represent a potential biomarker and an additional risk factor for the emergence of impulse control disorders. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Neuroimaging and neuromodulation approaches to study eating behavior and prevent and treat eating disorders and obesity

PubMed Central

Val-Laillet, D.; Aarts, E.; Weber, B.; Ferrari, M.; Quaresima, V.; Stoeckel, L.E.; Alonso-Alonso, M.; Audette, M.; Malbert, C.H.; Stice, E.

2015-01-01

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain–behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies. PMID:26110109

Network analysis reveals disrupted functional brain circuitry in drug-naive social anxiety disorder.

PubMed

Yang, Xun; Liu, Jin; Meng, Yajing; Xia, Mingrui; Cui, Zaixu; Wu, Xi; Hu, Xinyu; Zhang, Wei; Gong, Gaolang; Gong, Qiyong; Sweeney, John A; He, Yong

2017-12-07

Social anxiety disorder (SAD) is a common and disabling condition characterized by excessive fear and avoidance of public scrutiny. Psychoradiology studies have suggested that the emotional and behavior deficits in SAD are associated with abnormalities in regional brain function and functional connectivity. However, little is known about whether intrinsic functional brain networks in patients with SAD are topologically disrupted. Here, we collected resting-state fMRI data from 33 drug-naive patients with SAD and 32 healthy controls (HC), constructed functional networks with 34 predefined regions based on previous meta-analytic research with task-based fMRI in SAD, and performed network-based statistic and graph-theory analyses. The network-based statistic analysis revealed a single connected abnormal circuitry including the frontolimbic circuit (termed the "fear circuit", including the dorsolateral prefrontal cortex, ventral medial prefrontal cortex and insula) and posterior cingulate/occipital areas supporting perceptual processing. In this single altered network, patients with SAD had higher functional connectivity than HC. At the global level, graph-theory analysis revealed that the patients exhibited a lower normalized characteristic path length than HC, which suggests a disorder-related shift of network topology toward randomized configurations. SAD-related deficits in nodal degree, efficiency and participation coefficient were detected in the parahippocampal gyrus, posterior cingulate cortex, dorsolateral prefrontal cortex, insula and the calcarine sulcus. Aspects of abnormal connectivity were associated with anxiety symptoms. These findings highlight the aberrant topological organization of functional brain network organization in SAD, which provides insights into the neural mechanisms underlying excessive fear and avoidance of social interactions in patients with debilitating social anxiety. Copyright © 2017. Published by Elsevier Inc.

Neuroimaging is a novel tool to understand the impact of environmental chemicals on neurodevelopment.

PubMed

Horton, Megan K; Margolis, Amy E; Tang, Cheuk; Wright, Robert

2014-04-01

The prevalence of childhood neurodevelopmental disorders has been increasing over the last several decades. Prenatal and early childhood exposure to environmental toxicants is increasingly recognized as contributing to the growing rate of neurodevelopmental disorders. Very little information is known about the mechanistic processes by which environmental chemicals alter brain development. We review the recent advances in brain imaging modalities and discuss their application in epidemiologic studies of prenatal and early childhood exposure to environmental toxicants. Neuroimaging techniques (volumetric and functional MRI, diffusor tensor imaging, and magnetic resonance spectroscopy) have opened unprecedented access to study the developing human brain. These techniques are noninvasive and free of ionization radiation making them suitable for research applications in children. Using these techniques, we now understand much about structural and functional patterns in the typically developing brain. This knowledge allows us to investigate how prenatal exposure to environmental toxicants may alter the typical developmental trajectory. MRI is a powerful tool that allows in-vivo visualization of brain structure and function. Used in epidemiologic studies of environmental exposure, it offers the promise to causally link exposure with behavioral and cognitive manifestations and ultimately to inform programs to reduce exposure and mitigate adverse effects of exposure.

Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits.

PubMed

Pinsonneault, Julia K; Frater, John T; Kompa, Benjamin; Mascarenhas, Roshan; Wang, Danxin; Sadee, Wolfgang

2017-01-01

Genetic variants of ESR1 have been implicated in multiple diseases, including behavioral disorders, but causative variants remain uncertain. We have searched for regulatory variants affecting ESR1 expression in human brain, measuring allelic ESR1 mRNA expression in human brain tissues with marker SNPs in exon4 representing ESR1-008 (or ESRα-36), and in the 3'UTR of ESR1-203, two main ESR1 isoforms in brain. In prefrontal cortex from subjects with bipolar disorder, schizophrenia, and controls (n = 35 each; Stanley Foundation brain bank), allelic ESR1 mRNA ratios deviated from unity up to tenfold at the exon4 marker SNP, with large allelic ratios observed primarily in bipolar and schizophrenic subjects. SNP scanning and targeted sequencing identified rs2144025, associated with large allelic mRNA ratios (p = 1.6E10-6). Moreover, rs2144025 was significantly associated with ESR1 mRNA levels in the Brain eQTL Almanac and in brain regions in the Genotype-Tissue Expression project. In four GWAS cohorts, rs2104425 was significantly associated with behavioral traits, including: hypomanic episodes in female bipolar disorder subjects (GAIN bipolar disorder study; p = 0.0004), comorbid psychological symptoms in both males and females with attention deficit hyperactivity disorder (GAIN ADHD, p = 0.00002), psychological diagnoses in female children (eMERGE study of childhood health, subject age ≥9, p = 0.0009), and traits in schizophrenia (e.g., grandiose delusions, GAIN schizophrenia, p = 0.0004). The first common ESR1 variant (MAF 12-33% across races) linked to regulatory functions, rs2144025 appears conditionally to affect ESR1 mRNA expression in the brain and modulate traits in behavioral disorders.

Intronic SNP in ESR1 encoding human estrogen receptor alpha is associated with brain ESR1 mRNA isoform expression and behavioral traits

PubMed Central

Kompa, Benjamin; Mascarenhas, Roshan; Wang, Danxin; Sadee, Wolfgang

2017-01-01

Genetic variants of ESR1 have been implicated in multiple diseases, including behavioral disorders, but causative variants remain uncertain. We have searched for regulatory variants affecting ESR1 expression in human brain, measuring allelic ESR1 mRNA expression in human brain tissues with marker SNPs in exon4 representing ESR1-008 (or ESRα-36), and in the 3’UTR of ESR1-203, two main ESR1 isoforms in brain. In prefrontal cortex from subjects with bipolar disorder, schizophrenia, and controls (n = 35 each; Stanley Foundation brain bank), allelic ESR1 mRNA ratios deviated from unity up to tenfold at the exon4 marker SNP, with large allelic ratios observed primarily in bipolar and schizophrenic subjects. SNP scanning and targeted sequencing identified rs2144025, associated with large allelic mRNA ratios (p = 1.6E10-6). Moreover, rs2144025 was significantly associated with ESR1 mRNA levels in the Brain eQTL Almanac and in brain regions in the Genotype-Tissue Expression project. In four GWAS cohorts, rs2104425 was significantly associated with behavioral traits, including: hypomanic episodes in female bipolar disorder subjects (GAIN bipolar disorder study; p = 0.0004), comorbid psychological symptoms in both males and females with attention deficit hyperactivity disorder (GAIN ADHD, p = 0.00002), psychological diagnoses in female children (eMERGE study of childhood health, subject age ≥9, p = 0.0009), and traits in schizophrenia (e.g., grandiose delusions, GAIN schizophrenia, p = 0.0004). The first common ESR1 variant (MAF 12–33% across races) linked to regulatory functions, rs2144025 appears conditionally to affect ESR1 mRNA expression in the brain and modulate traits in behavioral disorders. PMID:28617822

Taste Reward Circuitry Related Brain Structures Characterize Ill and Recovered Anorexia Nervosa and Bulimia Nervosa

PubMed Central

Frank, Guido K.; Shott, Megan E.; Hagman, Jennifer O.; Mittal, Vijay A.

2013-01-01

Objective The pathophysiology of the eating disorder anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. Here we assessed taste pleasantness and reward sensitivity in relation to brain structure, which might be related to food avoidance commonly seen in eating disorders. Method We used structural magnetic resonance brain imaging to study gray and white matter volumes in individuals with restricting type currently ill (n = 19) or recovered-anorexia nervosa (n = 24), bulimia nervosa (n= 19) and healthy control women (n=24). Results All eating disorder groups showed increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manually tracing confirmed larger gyrus rectus volume, and predicted taste pleasantness across all groups. The analyses also indicated other morphological differences between diagnostic categories: Ill and recovered-anorexia nervosa had increased right, while bulimia nervosa had increased left antero-ventral insula gray matter volumes compared to controls. Furthermore, dorsal striatum volumes were reduced in recovered-anorexia and bulimia nervosa, and predicted sensitivity to reward in the eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas when compared to healthy controls. Notably, the results held when controlling for a range of covariates (e.g., age, depression, anxiety, medications). Conclusion Brain structure in medial orbitofrontal cortex, insula and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value. PMID:23680873

Variations of the Functional Brain Network Efficiency in a Young Clinical Sample within the Autism Spectrum: A fNIRS Investigation.

PubMed

Li, Yanwei; Yu, Dongchuan

2018-01-01

Autism is a neurodevelopmental disorder with dimensional behavioral symptoms and various damages in the structural and functional brain. Previous neuroimaging studies focused on exploring the differences of brain development between individuals with and without autism spectrum disorders (ASD). However, few of them have attempted to investigate the individual differences of the brain features among subjects within the Autism spectrum. Our main goal was to explore the individual differences of neurodevelopment in young children with Autism by testing for the association between the functional network efficiency and levels of autistic behaviors, as well as the association between the functional network efficiency and age. Forty-six children with Autism (ages 2.0-8.9 years old) participated in the current study, with levels of autistic behaviors evaluated by their parents. The network efficiency (global and local network efficiency) were obtained from the functional networks based on the oxy-, deoxy-, and total-Hemoglobin series, respectively. Results indicated that the network efficiency decreased with age in young children with Autism in the deoxy- and total-Hemoglobin-based-networks, and children with a relatively higher level of autistic behaviors showed decreased network efficiency in the oxy-hemoglobin-based network. Results suggest individual differences of brain development in young children within the Autism spectrum, providing new insights into the psychopathology of ASD.

Age-dependent association of thyroid function with brain morphology and microstructural organization: evidence from brain imaging.

PubMed

Chaker, Layal; Cremers, Lotte G M; Korevaar, Tim I M; de Groot, Marius; Dehghan, Abbas; Franco, Oscar H; Niessen, Wiro J; Ikram, M Arfan; Peeters, Robin P; Vernooij, Meike W

2018-01-01

Thyroid hormone (TH) is crucial during neurodevelopment, but high levels of TH have been linked to neurodegenerative disorders. No data on the association of thyroid function with brain imaging in the general population are available. We therefore investigated the association of thyroid-stimulating hormone and free thyroxine (FT4) with magnetic resonance imaging (MRI)-derived total intracranial volume, brain tissue volumes, and diffusion tensor imaging measures of white matter microstructure in 4683 dementia- and stroke-free participants (mean age 60.2, range 45.6-89.9 years). Higher FT4 levels were associated with larger total intracranial volumes (β = 6.73 mL, 95% confidence interval = 2.94-9.80). Higher FT4 levels were also associated with larger total brain and white matter volumes in younger individuals, but with smaller total brain and white matter volume in older individuals (p-interaction 0.02). There was a similar interaction by age for the association of FT4 with mean diffusivity on diffusion tensor imaging (p-interaction 0.026). These results are in line with differential effects of TH during neurodevelopmental and neurodegenerative processes and can improve the understanding of the role of thyroid function in neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Abnormal autonomic and associated brain activities during rest in autism spectrum disorder

PubMed Central

Eilam-Stock, Tehila; Xu, Pengfei; Cao, Miao; Gu, Xiaosi; Van Dam, Nicholas T.; Anagnostou, Evdokia; Kolevzon, Alexander; Soorya, Latha; Park, Yunsoo; Siller, Michael; He, Yong; Hof, Patrick R.

2014-01-01

Autism spectrum disorders are associated with social and emotional deficits, the aetiology of which are not well understood. A growing consensus is that the autonomic nervous system serves a key role in emotional processes, by providing physiological signals essential to subjective states. We hypothesized that altered autonomic processing is related to the socio-emotional deficits in autism spectrum disorders. Here, we investigated the relationship between non-specific skin conductance response, an objective index of sympathetic neural activity, and brain fluctuations during rest in high-functioning adults with autism spectrum disorder relative to neurotypical controls. Compared with control participants, individuals with autism spectrum disorder showed less skin conductance responses overall. They also showed weaker correlations between skin conductance responses and frontal brain regions, including the anterior cingulate and anterior insular cortices. Additionally, skin conductance responses were found to have less contribution to default mode network connectivity in individuals with autism spectrum disorders relative to controls. These results suggest that autonomic processing is altered in autism spectrum disorders, which may be related to the abnormal socio-emotional behaviours that characterize this condition. PMID:24424916

Reduced Activation in Right Lateral Prefrontal Cortex and Anterior Cingulate Gyrus in Medication-Naive Adolescents with Attention Deficit Hyperactivity Disorder during Time Discrimination

ERIC Educational Resources Information Center

Smith, Anna B.; Taylor, Eric; Brammer, Michael; Halari, Rozmin; Rubia, Katya

2008-01-01

Background: Patients with attention deficit hyperactivity disorder (ADHD) under-perform when discriminating between durations differing by several hundred milliseconds. This function involves right prefrontal and anterior cingulate (AC) brain regions, which are structurally and functionally compromised in this patient group during executive tasks.…

Developmental Meta-Analysis of the Functional Neural Correlates of Autism Spectrum Disorders

ERIC Educational Resources Information Center

Dickstein, Daniel P.; Pescosolido, Matthew F.; Reidy, Brooke L.; Galvan, Thania; Kim, Kerri L.; Seymour, Karen E.; Laird, Angela R.; Di Martino, Adriana; Barrett, Rowland P.

2013-01-01

Objective: There is a pressing need to elucidate the brain-behavior interactions underlying autism spectrum disorders (ASD) given the marked rise in ASD diagnosis over the past decade. Functional magnetic resonance imaging (fMRI) has begun to address this need, but few fMRI studies have evaluated age-related changes in ASD. Therefore, we conducted…

Deep brain stimulation for severe treatment-resistant obsessive-compulsive disorder: An open-label case series.

PubMed

Farrand, Sarah; Evans, Andrew H; Mangelsdorf, Simone; Loi, Samantha M; Mocellin, Ramon; Borham, Adam; Bevilacqua, JoAnne; Blair-West, Scott; Walterfang, Mark A; Bittar, Richard G; Velakoulis, Dennis

2017-09-01

Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8-54 months). The sample included four females and three males, with a mean age of 46 years (range, 37-59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15-38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Deep brain stimulation was an effective treatment for obsessive-compulsive disorder in these highly selected patients. The extent of the response to deep brain stimulation varied between patients, as well as during the course of treatment for each patient. The results of this series are comparable with the literature, as well as having similar efficacy to ablative psychosurgery techniques such as capsulotomy and cingulotomy. Deep brain stimulation provides advantages over lesional psychosurgery but is more expensive and requires significant multidisciplinary input at all stages, pre- and post-operatively, ideally within a specialised tertiary clinical and/or academic centre. Ongoing research is required to better understand the neurobiological basis for obsessive-compulsive disorder and how this can be manipulated with deep brain stimulation to further improve the efficacy of this emerging treatment.

Functional near infrared spectroscopy as a probe of brain function in people with prolonged disorders of consciousness.

PubMed

Kempny, Agnieszka M; James, Leon; Yelden, Kudret; Duport, Sophie; Farmer, Simon; Playford, E Diane; Leff, Alexander P

2016-01-01

Near infrared spectroscopy (NIRS) is a non-invasive technique which measures changes in brain tissue oxygenation. NIRS has been used for continuous monitoring of brain oxygenation during medical procedures carrying high risk of iatrogenic brain ischemia and also has been adopted by cognitive neuroscience for studies on executive and cognitive functions. Until now, NIRS has not been used to detect residual cognitive functions in patients with prolonged disorders of consciousness (pDOC). In this study we aimed to evaluate the brain function of patients with pDOC by using a motor imagery task while recording NIRS. We also collected data from a group of age and gender matched healthy controls while they carried out both real and imagined motor movements to command. We studied 16 pDOC patients in total, split into two groups: five had a diagnosis of Vegetative state/Unresponsive Wakefulness State, and eleven had a diagnosis of Minimally Conscious State. In the control subjects we found a greater oxy-haemoglobin (oxyHb) response during real movement compared with imagined movement. For the between group comparison, we found a main effect of hemisphere, with greater depression of oxyHb signal in the right > left hemisphere compared with rest period for all three groups. A post-hoc analysis including only the two pDOC patient groups was also significant suggesting that this effect was not just being driven by the control subjects. This study demonstrates for the first time the feasibility of using NIRS for the assessment of brain function in pDOC patients using a motor imagery task.

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.

Altered expression of BDNF, BDNF pro-peptide and their precursor proBDNF in brain and liver tissues from psychiatric disorders: rethinking the brain-liver axis.

PubMed

Yang, B; Ren, Q; Zhang, J-C; Chen, Q-X; Hashimoto, K

2017-05-16

Brain-derived neurotrophic factor (BDNF) has a role in the pathophysiology of psychiatric disorders. The precursor proBDNF is converted to mature BDNF and BDNF pro-peptide, the N-terminal fragment of proBDNF; however, the precise function of these proteins in psychiatric disorders is unknown. We sought to determine whether expression of these proteins is altered in the brain and peripheral tissues from patients with psychiatric disorders. We measured protein expression of proBDNF, mature BDNF and BDNF pro-peptide in the parietal cortex, cerebellum, liver and spleen from control, major depressive disorder (MDD), schizophrenia (SZ) and bipolar disorder (BD) groups. The levels of mature BDNF in the parietal cortex from MDD, SZ and BD groups were significantly lower than the control group, whereas the levels of BDNF pro-peptide in this area were significantly higher than controls. In contrast, the levels of proBDNF and BDNF pro-peptide in the cerebellum of MDD, SZ and BD groups were significantly lower than controls. Moreover, the levels of mature BDNF from the livers of MDD, SZ and BD groups were significantly higher than the control group. The levels of mature BDNF in the spleen did not differ among the four groups. Interestingly, there was a negative correlation between mature BDNF in the parietal cortex and mature BDNF in the liver in all the subjects. These findings suggest that abnormalities in the production of mature BDNF and BDNF pro-peptide in the brain and liver might have a role in the pathophysiology of psychiatric disorders, indicating a brain-liver axis in psychiatric disorders.

Functional Imaging and Migraine: New Connections?

PubMed Central

Schwedt, Todd J.; Chong, Catherine D.

2015-01-01

Purpose of Review Over the last several years, a growing number of brain functional imaging studies have provided insights into mechanisms underlying migraine. This manuscript reviews the recent migraine functional neuroimaging literature and provides recommendations for future studies that will help fill knowledge gaps. Recent Findings Positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies have identified brain regions that might be responsible for mediating the onset of a migraine attack and those associated with migraine symptoms. Enhanced activation of brain regions that facilitate processing of sensory stimuli suggests a mechanism by which migraineurs are hypersensitive to visual, olfactory, and cutaneous stimuli. Resting state functional connectivity MRI studies have identified numerous brain regions and functional networks with atypical functional connectivity in migraineurs, suggesting that migraine is associated with aberrant brain functional organization. Summary fMRI and PET studies that have identified brain regions and brain networks that are atypical in migraine have helped to describe the neurofunctional basis for migraine symptoms. Future studies should compare functional imaging findings in migraine to other headache and pain disorders and should explore the utility of functional imaging data as biomarkers for diagnostic and treatment purposes. PMID:25887764

The Role of Neuroimaging Techniques in Establishing Diagnosis, Prognosis and Therapy in Disorders of Consciousness

PubMed Central

Gosseries, Olivia; Pistoia, Francesca; Charland-Verville, Vanessa; Carolei, Antonio; Sacco, Simona; Laureys, Steven

2016-01-01

Non-communicative brain damaged patients raise important clinical and scientific issues. Here, we review three major pathological disorders of consciousness: coma, the unresponsive wakefulness syndrome and the minimally conscious state. A number of clinical studies highlight the difficulty in making a correct diagnosis in patients with disorders of consciousness based only on behavioral examinations. The increasing use of neuroimaging techniques allows improving clinical characterization of these patients. Recent neuroimaging studies using positron emission tomography, functional magnetic resonance imaging, electroencephalography and transcranial magnetic stimulation can help assess diagnosis, prognosis, and therapeutic treatment. These techniques, using resting state, passive and active paradigms, also highlight possible dissociations between consciousness and responsiveness, and are facilitating a more accurate understanding of brain function in this challenging population. PMID:27347265

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

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

Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder.

PubMed

Brinkmann, L; Buff, C; Feldker, K; Tupak, S V; Becker, M P I; Herrmann, M J; Straube, T

2017-11-01

Panic disorder (PD) patients are constantly concerned about future panic attacks and exhibit general hypersensitivity to unpredictable threat. We aimed to reveal phasic and sustained brain responses and functional connectivity of the amygdala and the bed nucleus of the stria terminalis (BNST) during threat anticipation in PD. Using functional magnetic resonance imaging (fMRI), we investigated 17 PD patients and 19 healthy controls (HC) during anticipation of temporally unpredictable aversive and neutral sounds. We used a phasic and sustained analysis model to disentangle temporally dissociable brain activations. PD patients compared with HC showed phasic amygdala and sustained BNST responses during anticipation of aversive v. neutral stimuli. Furthermore, increased phasic activation was observed in anterior cingulate cortex (ACC), insula and prefrontal cortex (PFC). Insula and PFC also showed sustained activation. Functional connectivity analyses revealed partly distinct phasic and sustained networks. We demonstrate a role for the BNST during unpredictable threat anticipation in PD and provide first evidence for dissociation between phasic amygdala and sustained BNST activation and their functional connectivity. In line with a hypersensitivity to uncertainty in PD, our results suggest time-dependent involvement of brain regions related to fear and anxiety.

Evaluating effects of methylphenidate on brain activity in cocaine addiction: a machine-learning approach

NASA Astrophysics Data System (ADS)

Rish, Irina; Bashivan, Pouya; Cecchi, Guillermo A.; Goldstein, Rita Z.

2016-03-01

The objective of this study is to investigate effects of methylphenidate on brain activity in individuals with cocaine use disorder (CUD) using functional MRI (fMRI). Methylphenidate hydrochloride (MPH) is an indirect dopamine agonist commonly used for treating attention deficit/hyperactivity disorders; it was also shown to have some positive effects on CUD subjects, such as improved stop signal reaction times associated with better control/inhibition,1 as well as normalized task-related brain activity2 and resting-state functional connectivity in specific areas.3 While prior fMRI studies of MPH in CUDs have focused on mass-univariate statistical hypothesis testing, this paper evaluates multivariate, whole-brain effects of MPH as captured by the generalization (prediction) accuracy of different classification techniques applied to features extracted from resting-state functional networks (e.g., node degrees). Our multivariate predictive results based on resting-state data from3 suggest that MPH tends to normalize network properties such as voxel degrees in CUD subjects, thus providing additional evidence for potential benefits of MPH in treating cocaine addiction.

Alterations in emotion generation and regulation neurocircuitry in depression and eating disorders: A comparative review of structural and functional neuroimaging studies.

PubMed

Donofry, Shannon D; Roecklein, Kathryn A; Wildes, Jennifer E; Miller, Megan A; Erickson, Kirk I

2016-09-01

Major depression and eating disorders (EDs) are highly co-morbid and may share liability. Impaired emotion regulation may represent a common etiological or maintaining mechanism. Research has demonstrated that depressed individuals and individuals with EDs exhibit impaired emotion regulation, with these impairments being associated with changes in brain structure and function. The goal of this review was to evaluate findings from neuroimaging studies of depression and EDs to determine whether there are overlapping alterations in the brain regions known to be involved in emotion regulation, evidence of which would aid in the diagnosis and treatment of these conditions. Our review of the literature suggests that depression and EDs exhibit common structural and functional alterations in brain regions involved in emotion regulation, including the amygdala, ventral striatum and nucleus accumbens, anterior cingulate cortex, insula, and dorsolateral prefrontal cortex. We present preliminary support for a shared etiological mechanism. Future studies should consider manipulating emotion regulation in a sample of individuals with depression and EDs to better characterize abnormalities in these brain circuits. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dopaminergic Neurotransmission in the Human Brain: New Lessons from Perturbation and Imaging

PubMed Central

Ko, Ji Hyun; Strafella, Antonio P.

2012-01-01

Dopamine plays an important role in several brain functions and is involved in the pathogenesis of several psychiatric and neurological disorders. Neuroimaging techniques such as positron emission tomography allow us to quantify dopaminergic activity in the living human brain. Combining these with brain stimulation techniques offers us the unique opportunity to tackle questions regarding region-specific neurochemical activity. Such studies may aid clinicians and scientists to disentangle neural circuitries within the human brain and thereby help them to understand the underlying mechanisms of a given function in relation to brain diseases. Furthermore, it may also aid the development of alternative treatment approaches for various neurological and psychiatric conditions. PMID:21536838

Rett syndrome and MeCP2.

PubMed

Liyanage, Vichithra R B; Rastegar, Mojgan

2014-06-01

Rett syndrome (RTT) is a severe and progressive neurological disorder, which mainly affects young females. Mutations of the methyl-CpG binding protein 2 (MECP2) gene are the most prevalent cause of classical RTT cases. MECP2 mutations or altered expression are also associated with a spectrum of neurodevelopmental disorders such as autism spectrum disorders with recent links to fetal alcohol spectrum disorders. Collectively, MeCP2 relation to these neurodevelopmental disorders highlights the importance of understanding the molecular mechanisms by which MeCP2 impacts brain development, mental conditions, and compromised brain function. Since MECP2 mutations were discovered to be the primary cause of RTT, a significant progress has been made in the MeCP2 research, with respect to the expression, function and regulation of MeCP2 in the brain and its contribution in RTT pathogenesis. To date, there have been intensive efforts in designing effective therapeutic strategies for RTT benefiting from mouse models and cells collected from RTT patients. Despite significant progress in MeCP2 research over the last few decades, there is still a knowledge gap between the in vitro and in vivo research findings and translating these findings into effective therapeutic interventions in human RTT patients. In this review, we will provide a synopsis of Rett syndrome as a severe neurological disorder and will discuss the role of MeCP2 in RTT pathophysiology.

The neurobiology of retinoic acid in affective disorders.

PubMed

Bremner, J Douglas; McCaffery, Peter

2008-02-15

Current models of affective disorders implicate alterations in norepinephrine, serotonin, dopamine, and CRF/cortisol; however treatments targeted at these neurotransmitters or hormones have led to imperfect resolution of symptoms, suggesting that the neurobiology of affective disorders is incompletely understood. Until now retinoids have not been considered as possible contributors to affective disorders. Retinoids represent a family of compounds derived from vitamin A that perform a large number of functions, many via the vitamin A product, retinoic acid. This signaling molecule binds to specific retinoic acid receptors in the brain which, like the glucocorticoid and thyroid hormone receptors, are part of the nuclear receptor superfamily and regulate gene transcription. Research in the field of retinoic acid in the CNS has focused on the developing brain, in part stimulated by the observation that isotretinoin (13-cis retinoic acid), an isomer of retinoic acid used in the treatment of acne, is highly teratogenic for the CNS. More recent work has suggested that retinoic acid may influence the adult brain; animal studies indicated that the administration of isotretinoin is associated with alterations in behavior as well as inhibition of neurogenesis in the hippocampus. Clinical evidence for an association between retinoids and depression includes case reports in the literature, studies of health care databases, and other sources. A preliminary PET study in human subjects showed that isotretinoin was associated with a decrease in orbitofrontal metabolism. Several studies have shown that the molecular components required for retinoic acid signaling are expressed in the adult brain; the overlap of brain areas implicated in retinoic acid function and stress and depression suggest that retinoids could play a role in affective disorders. This report reviews the evidence in this area and describes several systems that may be targets of retinoic acid and which contribute to the pathophysiology of depression.

The Neurobiology of Retinoic Acid in Affective Disorders

PubMed Central

Bremner, J Douglas; McCaffery, Peter

2009-01-01

Current models of affective disorders implicate alterations in norepinephrine, serotonin, dopamine, and CRF/cortisol; however treatments targeted at these neurotransmitters or hormones have led to imperfect resolution of symptoms, suggesting that the neurobiology of affective disorders is incompletely understood. Until now retinoids have not been considered as possible contributors to affective disorders. Retinoids represent a family of compounds derived from Vitamin A that perform a large number of functions, many via the vitamin A product, retinoic acid. This signaling molecule binds to specific retinoic acid receptors in the brain which, like the glucocorticoid and thyroid hormone receptors, are part of the nuclear receptor superfamily and regulate gene transcription. Research in the field of retinoic acid in the CNS has focused on the developing brain, in part stimulated by the observation that isotretinoin (13-cis retinoic acid), an isomer of retinoic acid used in the treatment of acne, is highly teratogenic for the CNS. More recent work has suggested that retinoic acid may influence the adult brain; animal studies indicated that the administration of isotretinoin is associated with alterations in behavior as well as inhibition of neurogenesis in the hippocampus. Clinical evidence for an association between retinoids and depression includes case reports in the literature, studies of health care databases, and other sources. A preliminary PET study in human subjects showed that isotretinoin was associated with a decrease in orbitofrontal metabolism. Several studies have shown that the molecular components required for retinoic acid signaling are expressed in the adult brain ; the overlap of brain areas implicated in retinoic acid function and stress and depression suggest that retinoids could play a role in affective disorders. This report reviews the evidence in this area and describes several systems that may be targets of retinoic acid and which contribute to the pathophysiology of depression. PMID:17707566

Roles of mTOR Signaling in Brain Development.

PubMed

Lee, Da Yong

2015-09-01

mTOR is a serine/threonine kinase composed of multiple protein components. Intracellular signaling of mTOR complexes is involved in many of physiological functions including cell survival, proliferation and differentiation through the regulation of protein synthesis in multiple cell types. During brain development, mTOR-mediated signaling pathway plays a crucial role in the process of neuronal and glial differentiation and the maintenance of the stemness of neural stem cells. The abnormalities in the activity of mTOR and its downstream signaling molecules in neural stem cells result in severe defects of brain developmental processes causing a significant number of brain disorders, such as pediatric brain tumors, autism, seizure, learning disability and mental retardation. Understanding the implication of mTOR activity in neural stem cells would be able to provide an important clue in the development of future brain developmental disorder therapies.

The neuropsychiatry of hyperkinetic movement disorders: insights from neuroimaging into the neural circuit bases of dysfunction.

PubMed

Hayhow, Bradleigh D; Hassan, Islam; Looi, Jeffrey C L; Gaillard, Francesco; Velakoulis, Dennis; Walterfang, Mark

2013-01-01

Movement disorders, particularly those associated with basal ganglia disease, have a high rate of comorbid neuropsychiatric illness. We consider the pathophysiological basis of the comorbidity between movement disorders and neuropsychiatric illness by 1) reviewing the epidemiology of neuropsychiatric illness in a range of hyperkinetic movement disorders, and 2) correlating findings to evidence from studies that have utilized modern neuroimaging techniques to investigate these disorders. In addition to diseases classically associated with basal ganglia pathology, such as Huntington disease, Wilson disease, the neuroacanthocytoses, and diseases of brain iron accumulation, we include diseases associated with pathology of subcortical white matter tracts, brain stem nuclei, and the cerebellum, such as metachromatic leukodystrophy, dentatorubropallidoluysian atrophy, and the spinocerebellar ataxias. Neuropsychiatric symptoms are integral to a thorough phenomenological account of hyperkinetic movement disorders. Drawing on modern theories of cortico-subcortical circuits, we argue that these disorders can be conceptualized as disorders of complex subcortical networks with distinct functional architectures. Damage to any component of these complex information-processing networks can have variable and often profound consequences for the function of more remote neural structures, creating a diverse but nonetheless rational pattern of clinical symptomatology.

Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

PubMed Central

Kelly, John R.; Kennedy, Paul J.; Cryan, John F.; Dinan, Timothy G.; Clarke, Gerard; Hyland, Niall P.

2015-01-01

The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a “leaky gut” may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function. PMID:26528128

Optical mapping of brain activation in gambling disorders

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Lin, Xiaohong

2018-02-01

In this study, fNIRS was utilized to identify the brain activation difference between pathological gamblers (PGs) and heathy controls (HCs). We inspected the hemodynamic changes in the prefrontal cortex using fNIRS recordings during the completion of executive function and decision making tasks. Our finding revealed that the PG and HC groups exhibited significant differences in brain activation.

Volumetric brain magnetic resonance imaging predicts functioning in bipolar disorder: A machine learning approach.

PubMed

Sartori, Juliana M; Reckziegel, Ramiro; Passos, Ives Cavalcante; Czepielewski, Leticia S; Fijtman, Adam; Sodré, Leonardo A; Massuda, Raffael; Goi, Pedro D; Vianna-Sulzbach, Miréia; Cardoso, Taiane de Azevedo; Kapczinski, Flávio; Mwangi, Benson; Gama, Clarissa S

2018-08-01

Neuroimaging studies have been steadily explored in Bipolar Disorder (BD) in the last decades. Neuroanatomical changes tend to be more pronounced in patients with repeated episodes. Although the role of such changes in cognition and memory is well established, daily-life functioning impairments bulge among the consequences of the proposed progression. The objective of this study was to analyze MRI volumetric modifications in BD and healthy controls (HC) as possible predictors of daily-life functioning through a machine learning approach. Ninety-four participants (35 DSM-IV BD type I and 59 HC) underwent clinical and functioning assessments, and structural MRI. Functioning was assessed using the Functioning Assessment Short Test (FAST). The machine learning analysis was used to identify possible candidates of regional brain volumes that could predict functioning status, through a support vector regression algorithm. Patients with BD and HC did not differ in age, education and marital status. There were significant differences between groups in gender, BMI, FAST score, and employment status. There was significant correlation between observed and predicted FAST score for patients with BD, but not for controls. According to the model, the brain structures volumes that could predict FAST scores were: left superior frontal cortex, left rostral medial frontal cortex, right white matter total volume and right lateral ventricle volume. The machine learning approach demonstrated that brain volume changes in MRI were predictors of FAST score in patients with BD and could identify specific brain areas related to functioning impairment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sex steroid hormones and brain function: PET imaging as a tool for research.

PubMed

Moraga-Amaro, R; van Waarde, A; Doorduin, J; de Vries, E F J

2018-02-01

Sex steroid hormones are major regulators of sexual characteristic among species. These hormones, however, are also produced in the brain. Steroidal hormone-mediated signalling via the corresponding hormone receptors can influence brain function at the cellular level and thus affect behaviour and higher brain functions. Altered steroid hormone signalling has been associated with psychiatric disorders, such as anxiety and depression. Neurosteroids are also considered to have a neuroprotective effect in neurodegenerative diseases. So far, the role of steroid hormone receptors in physiological and pathological conditions has mainly been investigated post mortem on animal or human brain tissues. To study the dynamic interplay between sex steroids, their receptors, brain function and behaviour in psychiatric and neurological disorders in a longitudinal manner, however, non-invasive techniques are needed. Positron emission tomography (PET) is a non-invasive imaging tool that is used to quantitatively investigate a variety of physiological and biochemical parameters in vivo. PET uses radiotracers aimed at a specific target (eg, receptor, enzyme, transporter) to visualise the processes of interest. In this review, we discuss the current status of the use of PET imaging for studying sex steroid hormones in the brain. So far, PET has mainly been investigated as a tool to measure (changes in) sex hormone receptor expression in the brain, to measure a key enzyme in the steroid synthesis pathway (aromatase) and to evaluate the effects of hormonal treatment by imaging specific downstream processes in the brain. Although validated radiotracers for a number of targets are still warranted, PET can already be a useful technique for steroid hormone research and facilitate the translation of interesting findings in animal studies to clinical trials in patients. © 2017 The Authors. Journal of Neuroendocrinology published by John Wiley & Sons Ltd on behalf of British Society for Neuroendocrinology.

Genetic variant for behavioral regulation factor of executive function and its possible brain mechanism in attention deficit hyperactivity disorder.

PubMed

Sun, Xiao; Wu, Zhaomin; Cao, Qingjiu; Qian, Ying; Liu, Yong; Yang, Binrang; Chang, Suhua; Yang, Li; Wang, Yufeng

2018-05-16

As a childhood-onset psychiatric disorder, attention deficit hyperactivity disorder (ADHD) is complicated by phenotypic and genetic heterogeneity. Lifelong executive function deficits in ADHD are described in many literatures and have been proposed as endophenotypes of ADHD. However, its genetic basis is still elusive. In this study, we performed a genome-wide association study of executive function, rated with Behavioral Rating Inventory of Executive Function (BRIEF), in ADHD children. We identified one significant variant (rs852004, P = 2.51e-08) for the overall score of BRIEF. The association analyses for each component of executive function found this locus was more associated with inhibit and monitor components. Further principle component analysis and confirmatory factor analysis provided an ADHD-specific executive function pattern including inhibit and monitor factors. SNP rs852004 was mainly associated with the Behavioral Regulation factor. Meanwhile, we found the significant locus was associated with ADHD symptom. The Behavioral Regulation factor mediated its effect on ADHD symptom. Functional magnetic resonance imaging (fMRI) analyses further showed evidence that this variant affected the activity of inhibition control related brain regions. It provided new insights for the genetic basis of executive function in ADHD.

Life and death of neurons in the aging brain

NASA Technical Reports Server (NTRS)

Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

1997-01-01

Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

Identification of alterations associated with age in the clustering structure of functional brain networks.

PubMed

Guzman, Grover E C; Sato, Joao R; Vidal, Maciel C; Fujita, Andre

2018-01-01

Initial studies using resting-state functional magnetic resonance imaging on the trajectories of the brain network from childhood to adulthood found evidence of functional integration and segregation over time. The comprehension of how healthy individuals' functional integration and segregation occur is crucial to enhance our understanding of possible deviations that may lead to brain disorders. Recent approaches have focused on the framework wherein the functional brain network is organized into spatially distributed modules that have been associated with specific cognitive functions. Here, we tested the hypothesis that the clustering structure of brain networks evolves during development. To address this hypothesis, we defined a measure of how well a brain region is clustered (network fitness index), and developed a method to evaluate its association with age. Then, we applied this method to a functional magnetic resonance imaging data set composed of 397 males under 31 years of age collected as part of the Autism Brain Imaging Data Exchange Consortium. As results, we identified two brain regions for which the clustering change over time, namely, the left middle temporal gyrus and the left putamen. Since the network fitness index is associated with both integration and segregation, our finding suggests that the identified brain region plays a role in the development of brain systems.

Primary Cilia as a Possible Link between Left-Right Asymmetry and Neurodevelopmental Diseases.

PubMed

Trulioff, Andrey; Ermakov, Alexander; Malashichev, Yegor

2017-01-25

Cilia have multiple functions in the development of the entire organism, and participate in the development and functioning of the central nervous system. In the last decade, studies have shown that they are implicated in the development of the visceral left-right asymmetry in different vertebrates. At the same time, some neuropsychiatric disorders, such as schizophrenia, autism, bipolar disorder, and dyslexia, are known to be associated with lateralization failure. In this review, we consider possible links in the mechanisms of determination of visceral asymmetry and brain lateralization, through cilia. We review the functions of seven genes associated with both cilia, and with neurodevelopmental diseases, keeping in mind their possible role in the establishment of the left-right brain asymmetry.

Primary Cilia as a Possible Link between Left-Right Asymmetry and Neurodevelopmental Diseases

PubMed Central

Trulioff, Andrey; Ermakov, Alexander; Malashichev, Yegor

2017-01-01

Cilia have multiple functions in the development of the entire organism, and participate in the development and functioning of the central nervous system. In the last decade, studies have shown that they are implicated in the development of the visceral left-right asymmetry in different vertebrates. At the same time, some neuropsychiatric disorders, such as schizophrenia, autism, bipolar disorder, and dyslexia, are known to be associated with lateralization failure. In this review, we consider possible links in the mechanisms of determination of visceral asymmetry and brain lateralization, through cilia. We review the functions of seven genes associated with both cilia, and with neurodevelopmental diseases, keeping in mind their possible role in the establishment of the left-right brain asymmetry. PMID:28125008

Recent advances in applying mass spectrometry and systems biology to determine brain dynamics.

PubMed

Scifo, Enzo; Calza, Giulio; Fuhrmann, Martin; Soliymani, Rabah; Baumann, Marc; Lalowski, Maciej

2017-06-01

Neurological disorders encompass various pathologies which disrupt normal brain physiology and function. Poor understanding of their underlying molecular mechanisms and their societal burden argues for the necessity of novel prevention strategies, early diagnostic techniques and alternative treatment options to reduce the scale of their expected increase. Areas covered: This review scrutinizes mass spectrometry based approaches used to investigate brain dynamics in various conditions, including neurodegenerative and neuropsychiatric disorders. Different proteomics workflows for isolation/enrichment of specific cell populations or brain regions, sample processing; mass spectrometry technologies, for differential proteome quantitation, analysis of post-translational modifications and imaging approaches in the brain are critically deliberated. Future directions, including analysis of cellular sub-compartments, targeted MS platforms (selected/parallel reaction monitoring) and use of mass cytometry are also discussed. Expert commentary: Here, we summarize and evaluate current mass spectrometry based approaches for determining brain dynamics in health and diseases states, with a focus on neurological disorders. Furthermore, we provide insight on current trends and new MS technologies with potential to improve this analysis.

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.

Neural substrates of cue reactivity and craving in gambling disorder

PubMed Central

Limbrick-Oldfield, E H; Mick, I; Cocks, R E; McGonigle, J; Sharman, S P; Goldstone, A P; Stokes, P R A; Waldman, A; Erritzoe, D; Bowden-Jones, H; Nutt, D; Lingford-Hughes, A; Clark, L

2017-01-01

Cue reactivity is an established procedure in addictions research for examining the subjective experience and neural basis of craving. This experiment sought to quantify cue-related brain responses in gambling disorder using personally tailored cues in conjunction with subjective craving, as well as a comparison with appetitive non-gambling stimuli. Participants with gambling disorder (n=19) attending treatment and 19 controls viewed personally tailored blocks of gambling-related cues, as well as neutral cues and highly appetitive (food) images during a functional magnetic resonance imaging (fMRI) scan performed ~2–3 h after a usual meal. fMRI analysis examined cue-related brain activity, cue-related changes in connectivity and associations with block-by-block craving ratings. Craving ratings in the participants with gambling disorder increased following gambling cues compared with non-gambling cues. fMRI analysis revealed group differences in left insula and anterior cingulate cortex, with the gambling disorder group showing greater reactivity to the gambling cues, but no differences to the food cues. In participants with gambling disorder, craving to gamble correlated positively with gambling cue-related activity in the bilateral insula and ventral striatum, and negatively with functional connectivity between the ventral striatum and the medial prefrontal cortex. Gambling cues, but not food cues, elicit increased brain responses in reward-related circuitry in individuals with gambling disorder (compared with controls), providing support for the incentive sensitization theory of addiction. Activity in the insula co-varied with craving intensity, and may be a target for interventions. PMID:28045460

Eating disorder psychopathology, brain structure, neuropsychological correlates and risk mechanisms in very preterm young adults.

PubMed

Micali, Nadia; Kothari, Radha; Nam, Kie Woo; Gioroukou, Elena; Walshe, Muriel; Allin, Matthew; Rifkin, Larry; Murray, Robin M; Nosarti, Chiara

2015-03-01

This study investigates the prevalence of eating disorder (ED) psychopathology, neuropsychological function, structural brain correlates and risk mechanisms in a prospective cohort of very preterm (VPT) young adults. We assessed ED psychopathology and neuropsychological correlates in 143 cohort individuals born at <33 weeks of gestation. Structural brain correlates and risk factors at birth, in childhood and adolescence, were investigated using prospectively collected data throughout childhood/adolescence. VPT-born individuals had high levels of ED psychopathology at age 21 years. Executive function did not correlate with ED symptomatology. VPT adults presenting with ED psychopathology had smaller grey matter volume at age 14/15 years in the left posterior cerebellum and smaller white matter volume in the fusiform gyrus bilaterally, compared with VPT adults with no ED psychopathology. Caesarean delivery predicted engaging in compensatory behaviours, and severe eating difficulty at age 14 years predicted ED symptomatology in young adulthood. VPT individuals are at risk for ED symptomatology, with evidence of associated structural alterations in posterior brain regions. Further prospective studies are needed to clarify the pathways that lead from perinatal/obstetric complications to ED and relevant neurobiological mechanisms. © 2015 The Authors. European Eating Disorders Review published by John Wiley &Sons, Ltd. © 2015 The Authors. European Eating Disorders Review published by John Wiley & Sons, Ltd.

Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders

PubMed Central

Breit, Sigrid; Kupferberg, Aleksandra; Rogler, Gerhard; Hasler, Gregor

2018-01-01

The vagus nerve represents the main component of the parasympathetic nervous system, which oversees a vast array of crucial bodily functions, including control of mood, immune response, digestion, and heart rate. It establishes one of the connections between the brain and the gastrointestinal tract and sends information about the state of the inner organs to the brain via afferent fibers. In this review article, we discuss various functions of the vagus nerve which make it an attractive target in treating psychiatric and gastrointestinal disorders. There is preliminary evidence that vagus nerve stimulation is a promising add-on treatment for treatment-refractory depression, posttraumatic stress disorder, and inflammatory bowel disease. Treatments that target the vagus nerve increase the vagal tone and inhibit cytokine production. Both are important mechanism of resiliency. The stimulation of vagal afferent fibers in the gut influences monoaminergic brain systems in the brain stem that play crucial roles in major psychiatric conditions, such as mood and anxiety disorders. In line, there is preliminary evidence for gut bacteria to have beneficial effect on mood and anxiety, partly by affecting the activity of the vagus nerve. Since, the vagal tone is correlated with capacity to regulate stress responses and can be influenced by breathing, its increase through meditation and yoga likely contribute to resilience and the mitigation of mood and anxiety symptoms. PMID:29593576

[Amusia].

PubMed

Midorikawa, Akira

2007-08-01

This report reviewed recent cases of amusia and drew the following conclusions. First, amusia is an ill-defined condition. The classical definition restricted amusia to musical disorders caused by brain lesions. By the end of the last century, however, some researchers included developmental or innate musical disorders in amusia. Second, although recent case reports were based on the classical schema of amusia, there have been an increasing number of case studies that have described more restricted and specific symptoms, such as receptive amusia for harmony or musical alexia for rhythm notation. Third, although we can now obtain more accurate information about the brain lesions, we have not taken advantage of this information. Traditionally, it has been thought that the pitch element of vocal performance is referred to the right frontal or temporal lobe. Lastly, the relationship between musical function and degenerative disease deserves attention. Degenerative diseases can cause either a musical deficit or, paradoxically, improve musical function. For example, the musical competence of some patients improved after selective atrophy of the left hemisphere. In conclusion, recent ideas concerning the relationship between music and the brain have been derived from patients with brain damage, developmental disorders, and degenerative diseases. However, there is a missing link with respect to amusia. We know a lot about the cognitive aspect of music, but the 'true' function of music from an evolutionary perspective, something that is lacking in amusia, is not known.

Reduced Global Functional Connectivity of the Medial Prefrontal Cortex in Major Depressive Disorder

PubMed Central

Murrough, James W.; Abdallah, Chadi G.; Anticevic, Alan; Collins, Katherine A.; Geha, Paul; Averill, Lynnette A.; Schwartz, Jaclyn; DeWilde, Kaitlin E.; Averill, Christopher; Yang, Genevieve Jia-wei; Wong, Edmund; Tang, Cheuk Y.; Krystal, John H.; Iosifescu, Dan V.; Charney, Dennis S.

2016-01-01

Background Major depressive disorder is a disabling neuropsychiatric condition that is associated with disrupted functional connectivity across brain networks. The precise nature of altered connectivity, however, remains incompletely understood. The current study was designed to examine the coherence of large-scale connectivity in depression using a recently developed technique termed global brain connectivity. Methods A total of 82 subjects, including medication-free patients with major depression (n=57) and healthy volunteers (n=25) underwent functional magnetic resonance imaging with resting data acquisition for functional connectivity analysis. Global brain connectivity was computed as the mean of each voxel’s time series correlation with every other voxel and compared between study groups. Relationships between global connectivity and depressive symptom severity measured using the Montgomery-Åsberg Depression Rating Scale were examined by means of linear correlation. Results Relative to the healthy group, patients with depression evidenced reduced global connectivity bilaterally within multiple regions of medial and lateral prefrontal cortex. The largest between-group difference was observed within the right subgenual anterior cingulate cortex, extending into ventromedial prefrontal cortex bilaterally (Hedges’ g = −1.48, p<0.000001). Within the depressed group, patients with the lowest connectivity evidenced the highest symptom severity within ventromedial prefrontal cortex (r = −0.47, p=0.0005). Conclusions Patients with major depressive evidenced abnormal large-scale functional coherence in the brain that was centered within the subgenual cingulate cortex, and medial prefrontal cortex more broadly. These data extend prior studies of connectivity in depression and demonstrate that functional disconnection of the medial prefrontal cortex is a key pathological feature of the disorder. PMID:27144347

Abnormal Brain Dynamics Underlie Speech Production in Children with Autism Spectrum Disorder.

PubMed

Pang, Elizabeth W; Valica, Tatiana; MacDonald, Matt J; Taylor, Margot J; Brian, Jessica; Lerch, Jason P; Anagnostou, Evdokia

2016-02-01

A large proportion of children with autism spectrum disorder (ASD) have speech and/or language difficulties. While a number of structural and functional neuroimaging methods have been used to explore the brain differences in ASD with regards to speech and language comprehension and production, the neurobiology of basic speech function in ASD has not been examined. Magnetoencephalography (MEG) is a neuroimaging modality with high spatial and temporal resolution that can be applied to the examination of brain dynamics underlying speech as it can capture the fast responses fundamental to this function. We acquired MEG from 21 children with high-functioning autism (mean age: 11.43 years) and 21 age- and sex-matched controls as they performed a simple oromotor task, a phoneme production task and a phonemic sequencing task. Results showed significant differences in activation magnitude and peak latencies in primary motor cortex (Brodmann Area 4), motor planning areas (BA 6), temporal sequencing and sensorimotor integration areas (BA 22/13) and executive control areas (BA 9). Our findings of significant functional brain differences between these two groups on these simple oromotor and phonemic tasks suggest that these deficits may be foundational and could underlie the language deficits seen in ASD. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

The social brain hypothesis of schizophrenia.

PubMed

Burns, Jonathan

2006-06-01

The social brain hypothesis is a useful heuristic for understanding schizophrenia. It focuses attention on the core Bleulerian concept of autistic alienation and is consistent with well-replicated findings of social brain dysfunction in schizophrenia as well as contemporary theories of human cognitive and brain evolution. The contributions of Heidegger, Merleau-Ponty and Wittgenstein allow us to arrive at a new "philosophy of interpersonal relatedness", which better reflects the "embodied mind" and signifies the end of Cartesian dualistic thinking. In this paper I review the evolution, development and neurobiology of the social brain - the anatomical and functional substrate for adaptive social behaviour and cognition. Functional imaging identifies fronto-temporal and fronto-parietal cortical networks as comprising the social brain, while the discovery of "mirror neurons" provides an understanding of social cognition at a cellular level. Patients with schizophrenia display abnormalities in a wide range of social cognition tasks such as emotion recognition, theory of mind and affective responsiveness. Furthermore, recent research indicates that schizophrenia is a disorder of functional and structural connectivity of social brain networks. These findings lend support to the claim that schizophrenia represents a costly by-product of social brain evolution in Homo sapiens. Individuals with this disorder find themselves seriously disadvantaged in the social arena and vulnerable to the stresses of their complex social environments. This state of "disembodiment" and interpersonal alienation is the core phenomenon of schizophrenia and the root cause of intolerable suffering in the lives of those affected.

The social brain hypothesis of schizophrenia

PubMed Central

BURNS, JONATHAN

2006-01-01

The social brain hypothesis is a useful heuristic for understanding schizophrenia. It focuses attention on the core Bleulerian concept of autistic alienation and is consistent with well-replicated findings of social brain dysfunction in schizophrenia as well as contemporary theories of human cognitive and brain evolution. The contributions of Heidegger, Merleau-Ponty and Wittgenstein allow us to arrive at a new "philosophy of interpersonal relatedness", which better reflects the "embodied mind" and signifies the end of Cartesian dualistic thinking. In this paper I review the evolution, development and neurobiology of the social brain - the anatomical and functional substrate for adaptive social behaviour and cognition. Functional imaging identifies fronto-temporal and fronto-parietal cortical networks as comprising the social brain, while the discovery of "mirror neurons" provides an understanding of social cognition at a cellular level. Patients with schizophrenia display abnormalities in a wide range of social cognition tasks such as emotion recognition, theory of mind and affective responsiveness. Furthermore, recent research indicates that schizophrenia is a disorder of functional and structural connectivity of social brain networks. These findings lend support to the claim that schizophrenia represents a costly by-product of social brain evolution in Homo sapiens. Individuals with this disorder find themselves seriously disadvantaged in the social arena and vulnerable to the stresses of their complex social environments. This state of "disembodiment" and interpersonal alienation is the core phenomenon of schizophrenia and the root cause of intolerable suffering in the lives of those affected. PMID:16946939

Brain-Computer Interfaces in Medicine

PubMed Central

Shih, Jerry J.; Krusienski, Dean J.; Wolpaw, Jonathan R.

2012-01-01

Brain-computer interfaces (BCIs) acquire brain signals, analyze them, and translate them into commands that are relayed to output devices that carry out desired actions. BCIs do not use normal neuromuscular output pathways. The main goal of BCI is to replace or restore useful function to people disabled by neuromuscular disorders such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. From initial demonstrations of electroencephalography-based spelling and single-neuron-based device control, researchers have gone on to use electroencephalographic, intracortical, electrocorticographic, and other brain signals for increasingly complex control of cursors, robotic arms, prostheses, wheelchairs, and other devices. Brain-computer interfaces may also prove useful for rehabilitation after stroke and for other disorders. In the future, they might augment the performance of surgeons or other medical professionals. Brain-computer interface technology is the focus of a rapidly growing research and development enterprise that is greatly exciting scientists, engineers, clinicians, and the public in general. Its future achievements will depend on advances in 3 crucial areas. Brain-computer interfaces need signal-acquisition hardware that is convenient, portable, safe, and able to function in all environments. Brain-computer interface systems need to be validated in long-term studies of real-world use by people with severe disabilities, and effective and viable models for their widespread dissemination must be implemented. Finally, the day-to-day and moment-to-moment reliability of BCI performance must be improved so that it approaches the reliability of natural muscle-based function. PMID:22325364

Resting state functional MRI reveals abnormal network connectivity in neurofibromatosis 1.

PubMed

Tomson, Steffie N; Schreiner, Matthew J; Narayan, Manjari; Rosser, Tena; Enrique, Nicole; Silva, Alcino J; Allen, Genevera I; Bookheimer, Susan Y; Bearden, Carrie E

2015-11-01

Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits, and autism spectrum disorders. As a single-gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relationships. While mouse models have elucidated molecular and cellular mechanisms underlying learning deficits associated with this mutation, little is known about functional brain architecture in human subjects with NF1. To address this question, we used resting state functional connectivity magnetic resonance imaging (rs-fcMRI) to elucidate the intrinsic network structure of 30 NF1 participants compared with 30 healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel statistical methods were employed to quantify differences in local connectivity (edge strength) and modularity structure, in combination with traditional global graph theory applications. Our findings suggest that individuals with NF1 have reduced anterior-posterior connectivity, weaker bilateral edges, and altered modularity clustering relative to healthy controls. Further, edge strength and modular clustering indices were correlated with IQ and internalizing symptoms. These findings suggest that Ras signaling disruption may lead to abnormal functional brain connectivity; further investigation into the functional consequences of these alterations in both humans and in animal models is warranted. © 2015 Wiley Periodicals, Inc.

Resting state functional MRI reveals abnormal network connectivity in Neurofibromatosis 1

PubMed Central

Tomson, S.N.; Schreiner, M.; Narayan, M.; Rosser, Tena; Enrique, Nicole; Silva, Alcino J.; Allen, G.I.; Bookheimer, S.Y.; Bearden, C.E.

2015-01-01

Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits and autism spectrum disorders. As a single gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relationships. While mouse models have elucidated molecular and cellular mechanisms underlying learning deficits associated with this mutation, little is known about functional brain architecture in human subjects with NF1. To address this question, we used resting state functional connectivity MRI (rs-fcMRI) to elucidate the intrinsic network structure of 30 NF1 participants compared with 30 healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel statistical methods were employed to quantify differences in local connectivity (edge strength) and modularity structure, in combination with traditional global graph theory applications. Our findings suggest that individuals with NF1 have reduced anterior-posterior connectivity, weaker bilateral edges, and altered modularity clustering relative to healthy controls. Further, edge strength and modular clustering indices were correlated with IQ and internalizing symptoms. These findings suggest that Ras signaling disruption may lead to abnormal functional brain connectivity; further investigation into the functional consequences of these alterations in both humans and in animal models is warranted. PMID:26304096

Functional (psychogenic) movement disorders: merging mind and brain.

PubMed

Edwards, Mark J; Bhatia, Kailash P

2012-03-01

Functional (psychogenic) movement disorders (FMD) are part of the wide spectrum of functional neurological disorders, which together account for over 16% of patients referred to neurology clinics. FMD have been described as a "crisis for neurology" and cause major challenges in terms of diagnosis and treatment. As with other functional disorders, a key issue is the absence of pathophysiological understanding. There has been an influential historical emphasis on causation by emotional trauma, which is not supported by epidemiological studies. The similarity between physical signs in functional disorders and those that occur in feigned illness has also raised important challenges for pathophysiological understanding and has challenged health professionals' attitudes toward patients with these disorders. However, physical signs and selected investigations can help clinicians to reach a positive diagnosis, and modern pathophysiological research is showing an appreciation of the importance of both physical and psychological factors in FMD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Neurobiology of dynamic psychotherapy: an integration possible?

PubMed

Mundo, Emanuela

2006-01-01

In the last decades, Kandel's innovative experiments have demonstrated that brain structures and synaptic connections are dynamic. Synapses can be modified by a wide variety of environmental factors, including learning and memory processes. The hypothesis that dynamic psychotherapy process involves memory and learning processes has opened the possibility of a dialogue between neuroscience and psychoanalysis and related psychotherapy techniques. The primary aim of the present article is to critically review the more recent data on neurobiological effects of dynamic psychotherapy in psychiatric disorders. Relevant literature has been selected using the databases currently available online (i.e., PubMed). The literature search has been limited to the past 10 years and to genetic, molecular biology, and neuroimaging studies that have addressed the issue of changes induced by psychotherapy. Most of the genetic studies on mental disorders have demonstrated that psychiatric conditions result from a complex interaction of genetic susceptibility and environmental effects. For none of the many psychiatric conditions investigated has a purely genetic background been found. Molecular biology studies have indicated that gene expression is influenced by several environmental factors, including early experiences, traumas, learning, and memory processes. Neuroimaging studies (using fMRI and PET) have found that not only cognitive but also dynamic psychotherapy has measurable effects on the brain. In addition, psychotherapy may modify brain function and metabolism in specific brain areas. Most of these studies have considered patients with major depressive disorders and compared the effects of psychotherapy with the effect of standard pharmacotherapy. In conclusion, recent results from neuroscience studies have suggested that dynamic psychotherapy has a significant impact on brain function and metabolism in specific brain areas. The possible applications and developments of this new area of research toward the conceptualization of an integrative approach to treatment of psychiatric disorders are discussed.

76 FR 55400 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-07

...: Integrative, Functional and Cognitive Neuroscience Integrated Review Group; Auditory System Study Section... Neuroscience Integrated Review Group; Neurotoxicology and Alcohol Study Section. Date: October 13, 2011. Time... Disorders and Clinical Neuroscience Integrated Review Group; Developmental Brain Disorders Study Section...

Mapping neurotransmitter networks with PET: an example on serotonin and opioid systems.

PubMed

Tuominen, Lauri; Nummenmaa, Lauri; Keltikangas-Järvinen, Liisa; Raitakari, Olli; Hietala, Jarmo

2014-05-01

All functions of the human brain are consequences of altered activity of specific neural pathways and neurotransmitter systems. Although the knowledge of "system level" connectivity in the brain is increasing rapidly, we lack "molecular level" information on brain networks and connectivity patterns. We introduce novel voxel-based positron emission tomography (PET) methods for studying internal neurotransmitter network structure and intercorrelations of different neurotransmitter systems in the human brain. We chose serotonin transporter and μ-opioid receptor for this analysis because of their functional interaction at the cellular level and similar regional distribution in the brain. Twenty-one healthy subjects underwent two consecutive PET scans using [(11)C]MADAM, a serotonin transporter tracer, and [(11)C]carfentanil, a μ-opioid receptor tracer. First, voxel-by-voxel "intracorrelations" (hub and seed analyses) were used to study the internal structure of opioid and serotonin systems. Second, voxel-level opioid-serotonin intercorrelations (between neurotransmitters) were computed. Regional μ-opioid receptor binding potentials were uniformly correlated throughout the brain. However, our analyses revealed nonuniformity in the serotonin transporter intracorrelations and identified a highly connected local network (midbrain-striatum-thalamus-amygdala). Regionally specific intercorrelations between the opioid and serotonin tracers were found in anteromedial thalamus, amygdala, anterior cingulate cortex, dorsolateral prefrontal cortex, and left parietal cortex, i.e., in areas relevant for several neuropsychiatric disorders, especially affective disorders. This methodology enables in vivo mapping of connectivity patterns within and between neurotransmitter systems. Quantification of functional neurotransmitter balances may be a useful approach in etiological studies of neuropsychiatric disorders and also in drug development as a biomarker-based rationale for targeted modulation of neurotransmitter networks. Copyright © 2013 Wiley Periodicals, Inc.

Working memory network alterations in high-functioning adolescents with an autism spectrum disorder.

PubMed

Barendse, Evelien M; Schreuder, Lisanne J; Thoonen, Geert; Hendriks, Marc P H; Kessels, Roy P C; Backes, Walter H; Aldenkamp, Albert P; Jansen, Jacobus F A

2018-02-01

People with autism spectrum disorder (ASD) typically have deficits in the working memory (WM) system. WM is found to be an essential chain in successfully navigating in the social world. We hypothesize that brain networks for WM have an altered network integrity in ASD compared to controls. Thirteen adolescents (one female) with autistic disorder (n = 1), Asperger's disorder (n = 7), or pervasive developmental disorder not otherwise specified (n = 5), and 13 typically developing healthy control adolescents (one female) participated in this study. Functional magnetic resonance imaging (MRI) was performed using an n-back task and in resting state. The analysis of the behavioral data revealed deficits in WM performance in ASD, but only when tested to the limit. Adolescents with ASD showed lower binary global efficiency in the WM network than the healthy control group with n-back and resting-state data. This correlated with diagnostic scores for total problems, reciprocity, and language. Adolescents with higher-functioning autism have difficulty with the WM system, which is typically compensated. Functional MRI markers of brain network organization in ASD are related to characteristics of autism as represented in diagnostic scores. Therefore, functional MRI provides neuronal correlates for memory difficulties in adolescents with ASD. © 2017 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.

Integrative Analysis of Brain Region-specific Shank3 Interactomes for Understanding the Heterogeneity of Neuronal Pathophysiology Related to SHANK3 Mutations

PubMed Central

Lee, Yeunkum; Kang, Hyojin; Lee, Bokyoung; Zhang, Yinhua; Kim, Yoonhee; Kim, Shinhyun; Kim, Won-Ki; Han, Kihoon

2017-01-01

Recent molecular genetic studies have identified 100s of risk genes for various neurodevelopmental and neuropsychiatric disorders. As the number of risk genes increases, it is becoming clear that different mutations of a single gene could cause different types of disorders. One of the best examples of such a gene is SHANK3, which encodes a core scaffold protein of the neuronal excitatory post-synapse. Deletions, duplications, and point mutations of SHANK3 are associated with autism spectrum disorders, intellectual disability, schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Nevertheless, how the different mutations of SHANK3 can lead to such phenotypic diversity remains largely unknown. In this study, we investigated whether Shank3 could form protein complexes in a brain region-specific manner, which might contribute to the heterogeneity of neuronal pathophysiology caused by SHANK3 mutations. To test this, we generated a medial prefrontal cortex (mPFC) Shank3 in vivo interactome consisting of 211 proteins, and compared this protein list with a Shank3 interactome previously generated from mixed hippocampal and striatal (HP+STR) tissues. Unexpectedly, we found that only 47 proteins (about 20%) were common between the two interactomes, while 164 and 208 proteins were specifically identified in the mPFC and HP+STR interactomes, respectively. Each of the mPFC- and HP+STR-specific Shank3 interactomes represents a highly interconnected network. Upon comparing the brain region-enriched proteomes, we found that the large difference between the mPFC and HP+STR Shank3 interactomes could not be explained by differential protein expression profiles among the brain regions. Importantly, bioinformatic pathway analysis revealed that the representative biological functions of the mPFC- and HP+STR-specific Shank3 interactomes were different, suggesting that these interactors could mediate the brain region-specific functions of Shank3. Meanwhile, the same analysis on the common Shank3 interactors, including Homer and GKAP/SAPAP proteins, suggested that they could mainly function as scaffolding proteins at the post-synaptic density. Lastly, we found that the mPFC- and HP+STR-specific Shank3 interactomes contained a significant number of proteins associated with neurodevelopmental and neuropsychiatric disorders. These results suggest that Shank3 can form protein complexes in a brain region-specific manner, which might contribute to the pathophysiological and phenotypic diversity of disorders related to SHANK3 mutations. PMID:28469556

Laterality patterns of brain functional connectivity: gender effects.

PubMed

Tomasi, Dardo; Volkow, Nora D

2012-06-01

Lateralization of brain connectivity may be essential for normal brain function and may be sexually dimorphic. Here, we study the laterality patterns of short-range (implicated in functional specialization) and long-range (implicated in functional integration) connectivity and the gender effects on these laterality patterns. Parallel computing was used to quantify short- and long-range functional connectivity densities in 913 healthy subjects. Short-range connectivity was rightward lateralized and most asymmetrical in areas around the lateral sulcus, whereas long-range connectivity was rightward lateralized in lateral sulcus and leftward lateralizated in inferior prefrontal cortex and angular gyrus. The posterior inferior occipital cortex was leftward lateralized (short- and long-range connectivity). Males had greater rightward lateralization of brain connectivity in superior temporal (short- and long-range), inferior frontal, and inferior occipital cortices (short-range), whereas females had greater leftward lateralization of long-range connectivity in the inferior frontal cortex. The greater lateralization of the male's brain (rightward and predominantly short-range) may underlie their greater vulnerability to disorders with disrupted brain asymmetries (schizophrenia, autism).

Laterality Patterns of Brain Functional Connectivity: Gender Effects

PubMed Central

Tomasi, Dardo; Volkow, Nora D.

2012-01-01

Lateralization of brain connectivity may be essential for normal brain function and may be sexually dimorphic. Here, we study the laterality patterns of short-range (implicated in functional specialization) and long-range (implicated in functional integration) connectivity and the gender effects on these laterality patterns. Parallel computing was used to quantify short- and long-range functional connectivity densities in 913 healthy subjects. Short-range connectivity was rightward lateralized and most asymmetrical in areas around the lateral sulcus, whereas long-range connectivity was rightward lateralized in lateral sulcus and leftward lateralizated in inferior prefrontal cortex and angular gyrus. The posterior inferior occipital cortex was leftward lateralized (short- and long-range connectivity). Males had greater rightward lateralization of brain connectivity in superior temporal (short- and long-range), inferior frontal, and inferior occipital cortices (short-range), whereas females had greater leftward lateralization of long-range connectivity in the inferior frontal cortex. The greater lateralization of the male's brain (rightward and predominantly short-range) may underlie their greater vulnerability to disorders with disrupted brain asymmetries (schizophrenia, autism). PMID:21878483

Atypical within- and between-hemisphere motor network functional connections in children with developmental coordination disorder and attention-deficit/hyperactivity disorder.

PubMed

McLeod, Kevin R; Langevin, Lisa Marie; Dewey, Deborah; Goodyear, Bradley G

2016-01-01

Developmental coordination disorder (DCD) and attention-deficit hyperactivity disorder (ADHD) are highly comorbid neurodevelopmental disorders; however, the neural mechanisms of this comorbidity are poorly understood. Previous research has demonstrated that children with DCD and ADHD have altered brain region communication, particularly within the motor network. The structure and function of the motor network in a typically developing brain exhibits hemispheric dominance. It is plausible that functional deficits observed in children with DCD and ADHD are associated with neurodevelopmental alterations in within- and between-hemisphere motor network functional connection strength that disrupt this hemispheric dominance. We used resting-state functional magnetic resonance imaging to examine functional connections of the left and right primary and sensory motor (SM1) cortices in children with DCD, ADHD and DCD + ADHD, relative to typically developing children. Our findings revealed that children with DCD, ADHD and DCD + ADHD exhibit atypical within- and between-hemisphere functional connection strength between SM1 and regions of the basal ganglia, as well as the cerebellum. Our findings further support the assertion that development of atypical motor network connections represents common and distinct neural mechanisms underlying DCD and ADHD. In children with DCD and DCD + ADHD (but not ADHD), a significant correlation was observed between clinical assessment of motor function and the strength of functional connections between right SM1 and anterior cingulate cortex, supplementary motor area, and regions involved in visuospatial processing. This latter finding suggests that behavioral phenotypes associated with atypical motor network development differ between individuals with DCD and those with ADHD.

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.

Brief Report: Alterations in Cerebral Blood Flow as Assessed by PET/CT in Adults with Autism Spectrum Disorder with Normal IQ

ERIC Educational Resources Information Center

Pagani, Marco; Manouilenko, Irina; Stone-Elander, Sharon; Odh, Richard; Salmaso, Dario; Hatherly, Robert; Brolin, Fredrik; Jacobsson, Hans; Larsson, Stig A.; Bejerot, Susanne

2012-01-01

Specific biological markers for Autism Spectrum Disorder (ASD) have not yet been established. Functional studies have shown abnormalities in the anatomo-functional connectivity of the limbic-striatal "social" brain. This study aimed to investigate regional cerebral blood flow (rCBF) at rest. Thirteen patients with ASD of normal intelligence and…

Neuroethics and Disorders of Consciousness: Discerning Brain States in Clinical Practice and Research.

PubMed

Fins, Joseph J

2016-12-01

Decisions about end-of-life care and participation in clinical research for patients with disorders of consciousness begin with diagnostic discernment. Accurately distinguishing between brain states clarifies clinicians' ethical obligations and responsibilities. Central to this effort is the obligation to provide neuropalliative care for patients in the minimally conscious state who can perceive pain and to restore functional communication through neuroprosthetics, drugs, and rehabilitation to patients with intact but underactivated neural networks. Efforts to bring scientific advances to patients with disorders of consciousness are reviewed, including the investigational use of deep brain stimulation in patients in the minimally conscious state. These efforts help to affirm the civil rights of a population long on the margins. © 2016 American Medical Association. All Rights Reserved.

Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: an integrative review.

PubMed

Eng, Goi Khia; Sim, Kang; Chen, Shen-Hsing Annabel

2015-05-01

Obsessive-compulsive disorder (OCD) is a debilitating disorder. However, existing neuroimaging findings involving executive function and structural abnormalities in OCD have been mixed. Here we conducted meta-analyses to investigate differences in OCD samples and controls in: Study 1 - grey matter structure; Study 2 - executive function task-related activations during (i) response inhibition, (ii) interference, and (iii) switching tasks; and Study 3 - white matter diffusivity. Results showed grey matter differences in the frontal, striatal, thalamus, parietal and cerebellar regions; task domain-specific neural differences in similar regions; and abnormal diffusivity in major white matter regions in OCD samples compared to controls. Our results reported concurrence of abnormal white matter diffusivity with corresponding abnormalities in grey matter and task-related functional activations. Our findings suggested the involvement of other brain regions not included in the cortico-striato-thalamo-cortical network, such as the cerebellum and parietal cortex, and questioned the involvement of the orbitofrontal region in OCD pathophysiology. Future research is needed to clarify the roles of these brain regions in the disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association of the brain-derived neurotrophic factor Val66Met polymorphism with negative symptoms severity, but not cognitive function, in first-episode schizophrenia spectrum disorders.

PubMed

Mezquida, G; Penadés, R; Cabrera, B; Savulich, G; Lobo, A; González-Pinto, A; Penzol, M J; Corripio, I; Fernandez-Egea, E; Gassó, P; Cuesta, M J; Bernardo, M

2016-10-01

A functional polymorphism of the brain-derived neurotrophic factor gene (BDNF) Val66Met has been associated with cognitive function and symptom severity in patients with schizophrenia. It has been suggested that the Val66Met polymorphism has a role as a modulator in a range of clinical features of the illness, including symptoms severity, therapeutic responsiveness, age of onset, brain morphology and cognitive function. However, little work has been done in first-episode schizophrenia (FES) spectrum disorders. The objective of this study is to investigate the association of the BDNF Val66Met polymorphism on cognitive function and clinical symptomatology in FES patients. Using a cross-sectional design in a cohort of 204 patients with FES or a schizophrenia spectrum disorder and 204 healthy matched controls, we performed BDNF Val66Met genotyping and tested its relationship with cognitive testing (attention, working memory, learning/verbal memory and reasoning/problem-solving) and assessment of clinical symptom severity. There was no significant influence of the BDNF allele frequency on cognitive factor scores in either patients or controls. An augmented severity of negative symptoms was found in FES patients that carried the Met allele. The results of this study suggest that in patients with a first-episode of schizophrenia or a schizophrenia spectrum disorder, the BDNF Val66Met polymorphism does not exert an influence on cognitive functioning, but is associated with negative symptoms severity. BDNF may serve as suitable marker of negative symptomatology severity in FES patients within the schizophrenia spectrum. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A chronological expression profile of gene activity during embryonic mouse brain development.

PubMed

Goggolidou, P; Soneji, S; Powles-Glover, N; Williams, D; Sethi, S; Baban, D; Simon, M M; Ragoussis, I; Norris, D P

2013-12-01

The brain is a functionally complex organ, the patterning and development of which are key to adult health. To help elucidate the genetic networks underlying mammalian brain patterning, we conducted detailed transcriptional profiling during embryonic development of the mouse brain. A total of 2,400 genes were identified as showing differential expression between three developmental stages. Analysis of the data identified nine gene clusters to demonstrate analogous expression profiles. A significant group of novel genes of as yet undiscovered biological function were detected as being potentially relevant to brain development and function, in addition to genes that have previously identified roles in the brain. Furthermore, analysis for genes that display asymmetric expression between the left and right brain hemispheres during development revealed 35 genes as putatively asymmetric from a combined data set. Our data constitute a valuable new resource for neuroscience and neurodevelopment, exposing possible functional associations between genes, including novel loci, and encouraging their further investigation in human neurological and behavioural disorders.

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.

Neurodegeneration with brain iron accumulation: update on pathogenic mechanisms

PubMed Central

Levi, Sonia; Finazzi, Dario

2014-01-01

Perturbation of iron distribution is observed in many neurodegenerative disorders, including Alzheimer’s and Parkinson’s disease, but the comprehension of the metal role in the development and progression of such disorders is still very limited. The combination of more powerful brain imaging techniques and faster genomic DNA sequencing procedures has allowed the description of a set of genetic disorders characterized by a constant and often early accumulation of iron in specific brain regions and the identification of the associated genes; these disorders are now collectively included in the category of neurodegeneration with brain iron accumulation (NBIA). So far 10 different genetic forms have been described but this number is likely to increase in short time. Two forms are linked to mutations in genes directly involved in iron metabolism: neuroferritinopathy, associated to mutations in the FTL gene and aceruloplasminemia, where the ceruloplasmin gene product is defective. In the other forms the connection with iron metabolism is not evident at all and the genetic data let infer the involvement of other pathways: Pank2, Pla2G6, C19orf12, COASY, and FA2H genes seem to be related to lipid metabolism and to mitochondria functioning, WDR45 and ATP13A2 genes are implicated in lysosomal and autophagosome activity, while the C2orf37 gene encodes a nucleolar protein of unknown function. There is much hope in the scientific community that the study of the NBIA forms may provide important insight as to the link between brain iron metabolism and neurodegenerative mechanisms and eventually pave the way for new therapeutic avenues also for the more common neurodegenerative disorders. In this work, we will review the most recent findings in the molecular mechanisms underlining the most common forms of NBIA and analyze their possible link with brain iron metabolism. PMID:24847269

Machine Learning Classification Combining Multiple Features of A Hyper-Network of fMRI Data in Alzheimer's Disease

PubMed Central

Guo, Hao; Zhang, Fan; Chen, Junjie; Xu, Yong; Xiang, Jie

2017-01-01

Exploring functional interactions among various brain regions is helpful for understanding the pathological underpinnings of neurological disorders. Brain networks provide an important representation of those functional interactions, and thus are widely applied in the diagnosis and classification of neurodegenerative diseases. Many mental disorders involve a sharp decline in cognitive ability as a major symptom, which can be caused by abnormal connectivity patterns among several brain regions. However, conventional functional connectivity networks are usually constructed based on pairwise correlations among different brain regions. This approach ignores higher-order relationships, and cannot effectively characterize the high-order interactions of many brain regions working together. Recent neuroscience research suggests that higher-order relationships between brain regions are important for brain network analysis. Hyper-networks have been proposed that can effectively represent the interactions among brain regions. However, this method extracts the local properties of brain regions as features, but ignores the global topology information, which affects the evaluation of network topology and reduces the performance of the classifier. This problem can be compensated by a subgraph feature-based method, but it is not sensitive to change in a single brain region. Considering that both of these feature extraction methods result in the loss of information, we propose a novel machine learning classification method that combines multiple features of a hyper-network based on functional magnetic resonance imaging in Alzheimer's disease. The method combines the brain region features and subgraph features, and then uses a multi-kernel SVM for classification. This retains not only the global topological information, but also the sensitivity to change in a single brain region. To certify the proposed method, 28 normal control subjects and 38 Alzheimer's disease patients were selected to participate in an experiment. The proposed method achieved satisfactory classification accuracy, with an average of 91.60%. The abnormal brain regions included the bilateral precuneus, right parahippocampal gyrus\\hippocampus, right posterior cingulate gyrus, and other regions that are known to be important in Alzheimer's disease. Machine learning classification combining multiple features of a hyper-network of functional magnetic resonance imaging data in Alzheimer's disease obtains better classification performance. PMID:29209156

Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders.

PubMed

Arnsten, Amy F T; Rubia, Katya

2012-04-01

This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Studies of animals, normally developing children, and patients with neurodevelopmental disorders were reviewed, with focus on neuroimaging studies. The PFC provides "top-down" regulation of attention, inhibition/cognitive control, motivation, and emotion through connections with posterior cortical and subcortical structures. Dorsolateral and inferior PFC regulate attention and cognitive/inhibitory control, whereas orbital and ventromedial structures regulate motivation and affect. PFC circuitries are very sensitive to their neurochemical environment, and small changes in the underlying neurotransmitter systems, e.g. by medications, can produce large effects on mediated function. Neuroimaging studies of children with neurodevelopmental disorders show altered brain structure and function in distinctive circuits respecting this organization. Children with attention-deficit/hyperactivity disorder show prominent abnormalities in the inferior PFC and its connections to striatal, cerebellar, and parietal regions, whereas children with conduct disorder show alterations in the paralimbic system, comprising ventromedial, lateral orbitofrontal, and superior temporal cortices together with specific underlying limbic regions, regulating motivation and emotion control. Children with major depressive disorder show alterations in ventral orbital and limbic activity, particularly in the left hemisphere, mediating emotions. Finally, children with obsessive-compulsive disorder appear to have a dysregulation in orbito-fronto-striatal inhibitory control pathways, but also deficits in dorsolateral fronto-parietal systems of attention. Altogether, there is a good correspondence between anatomical circuitry mediating compromised functions and patterns of brain structure and function changes in children with neuropsychiatric disorders. Medications may optimize the neurochemical environment in PFC and associated circuitries, and improve structure and function. Copyright © 2012 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Impact of a cis-associated gene expression SNP on chromosome 20q11.22 on bipolar disorder susceptibility, hippocampal structure and cognitive performance.

PubMed

Li, Ming; Luo, Xiong-jian; Landén, Mikael; Bergen, Sarah E; Hultman, Christina M; Li, Xiao; Zhang, Wen; Yao, Yong-Gang; Zhang, Chen; Liu, Jiewei; Mattheisen, Manuel; Cichon, Sven; Mühleisen, Thomas W; Degenhardt, Franziska A; Nöthen, Markus M; Schulze, Thomas G; Grigoroiu-Serbanescu, Maria; Li, Hao; Fuller, Chris K; Chen, Chunhui; Dong, Qi; Chen, Chuansheng; Jamain, Stéphane; Leboyer, Marion; Bellivier, Frank; Etain, Bruno; Kahn, Jean-Pierre; Henry, Chantal; Preisig, Martin; Kutalik, Zoltán; Castelao, Enrique; Wright, Adam; Mitchell, Philip B; Fullerton, Janice M; Schofield, Peter R; Montgomery, Grant W; Medland, Sarah E; Gordon, Scott D; Martin, Nicholas G; Rietschel, Marcella; Liu, Chunyu; Kleinman, Joel E; Hyde, Thomas M; Weinberger, Daniel R; Su, Bing

2016-02-01

Bipolar disorder is a highly heritable polygenic disorder. Recent enrichment analyses suggest that there may be true risk variants for bipolar disorder in the expression quantitative trait loci (eQTL) in the brain. We sought to assess the impact of eQTL variants on bipolar disorder risk by combining data from both bipolar disorder genome-wide association studies (GWAS) and brain eQTL. To detect single nucleotide polymorphisms (SNPs) that influence expression levels of genes associated with bipolar disorder, we jointly analysed data from a bipolar disorder GWAS (7481 cases and 9250 controls) and a genome-wide brain (cortical) eQTL (193 healthy controls) using a Bayesian statistical method, with independent follow-up replications. The identified risk SNP was then further tested for association with hippocampal volume (n = 5775) and cognitive performance (n = 342) among healthy individuals. Integrative analysis revealed a significant association between a brain eQTL rs6088662 on chromosome 20q11.22 and bipolar disorder (log Bayes factor = 5.48; bipolar disorder P = 5.85 × 10(-5)). Follow-up studies across multiple independent samples confirmed the association of the risk SNP (rs6088662) with gene expression and bipolar disorder susceptibility (P = 3.54 × 10(-8)). Further exploratory analysis revealed that rs6088662 is also associated with hippocampal volume and cognitive performance in healthy individuals. Our findings suggest that 20q11.22 is likely a risk region for bipolar disorder; they also highlight the informative value of integrating functional annotation of genetic variants for gene expression in advancing our understanding of the biological basis underlying complex disorders, such as bipolar disorder. © The Royal College of Psychiatrists 2016.

Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z

PubMed Central

Badgaiyan, Rajendra D.; Thanos, Panayotis K.; Kulkarni, Praveen; Giordano, John; Baron, David; Gold, Mark S.

2017-01-01

Dopaminergic reward dysfunction in addictive behaviors is well supported in the literature. There is evidence that alterations in synchronous neural activity between brain regions subserving reward and various cognitive functions may significantly contribute to substance-related disorders. This study presents the first evidence showing that a pro-dopaminergic nutraceutical (KB220Z) significantly enhances, above placebo, functional connectivity between reward and cognitive brain areas in the rat. These include the nucleus accumbens, anterior cingulate gyrus, anterior thalamic nuclei, hippocampus, prelimbic and infralimbic loci. Significant functional connectivity, increased brain connectivity volume recruitment (potentially neuroplasticity), and dopaminergic functionality were found across the brain reward circuitry. Increases in functional connectivity were specific to these regions and were not broadly distributed across the brain. While these initial findings have been observed in drug naïve rodents, this robust, yet selective response implies clinical relevance for addicted individuals at risk for relapse, who show reductions in functional connectivity after protracted withdrawal. Future studies will evaluate KB220Z in animal models of addiction. PMID:28445527

Psychoradiology: The Frontier of Neuroimaging in Psychiatry

PubMed Central

Lui, Su; Zhou, Xiaohong Joe; Sweeney, John A.

2016-01-01

Unlike neurologic conditions, such as brain tumors, dementia, and stroke, the neural mechanisms for all psychiatric disorders remain unclear. A large body of research obtained with structural and functional magnetic resonance imaging, positron emission tomography/single photon emission computed tomography, and optical imaging has demonstrated regional and illness-specific brain changes at the onset of psychiatric disorders and in individuals at risk for such disorders. Many studies have shown that psychiatric medications induce specific measurable changes in brain anatomy and function that are related to clinical outcomes. As a result, a new field of radiology, termed psychoradiology, seems primed to play a major clinical role in guiding diagnostic and treatment planning decisions in patients with psychiatric disorders. This article will present the state of the art in this area, as well as perspectives regarding preparations in the field of radiology for its evolution. Furthermore, this article will (a) give an overview of the imaging and analysis methods for psychoradiology; (b) review the most robust and important radiologic findings and their potential clinical value from studies of major psychiatric disorders, such as depression and schizophrenia; and (c) describe the main challenges and future directions in this field. An ongoing and iterative process of developing biologically based nomenclatures with which to delineate psychiatric disorders and translational research to predict and track response to different therapeutic drugs is laying the foundation for a shift in diagnostic practice in psychiatry from a psychologic symptom–based approach to an imaging-based approach over the next generation. This shift will require considerable innovations for the acquisition, analysis, and interpretation of brain images, all of which will undoubtedly require the active involvement of radiologists. © RSNA, 2016 Online supplemental material is available for this article. PMID:27755933

Toxoplasma gondii-A Gastrointestinal Pathogen Associated with Human Brain Diseases.

PubMed

Severance, E G; Xiao, J; Jones-Brando, L; Sabunciyan, S; Li, Y; Pletnikov, M; Prandovszky, E; Yolken, R

2016-01-01

Serious psychiatric disorders such as schizophrenia, bipolar disorder, and major depression are important causes of mortality and morbidity worldwide. While these are primarily diseases involving altered brain functioning, numerous studies have documented increased rates of gastrointestinal inflammation and dysfunction in many individuals with these disorders. Toxoplasma gondii is an apicomplexan protozoan intracellular parasite with a widespread distribution in both developed and developing countries. Toxoplasma organisms enter the ecosystem through the shedding of oocysts by Toxoplasma-infected felines. In almost all cases of postnatal human infection, Toxoplasma enters its hosts through the intestinal tract either by the ingestion of oocysts or by the consumption of meat from food animals which themselves were infected by Toxoplasma oocysts. It had previously been thought that most cases of Toxoplasma infection in immune competent children and adults were inapparent and asymptomatic. However, recent studies cast doubt on this concept as exposure to Toxoplasma has been associated with a range of acute and chronic symptoms. Of particular note has been the finding of an increased rate of a range of neurological and psychiatric disorders associated with serological evidence of Toxoplasma exposure. A role of Toxoplasma infection in brain diseases is also supported by the consistent finding of altered cognition and behavior in animal models of infections. Much of the attention relating to the role of Toxoplasma infection in neuropsychiatric disorders has focused on the brain, where Toxoplasma tissue cysts can persist for extended periods of time. However, recent discoveries relating to the role of the gastrointestinal tract in cognition and behavior suggest that Toxoplasma may also increase susceptibility to human brain diseases through immune activation, particularly involving the gastrointestinal mucosa. The study of the pathways relating to the pathobiology and immunology of Toxoplasma infection may provide insights into the pathogenesis of a range of human neuropsychiatric disorders as well as into cognitive functioning in otherwise healthy individuals. © 2016 Elsevier Inc. All rights reserved.

Targeting the brain--surmounting or bypassing the blood-brain barrier.

PubMed

Potschka, Heidrun

2010-01-01

The constituents of the blood-brain barrier, including its efflux transporter system, can efficiently limit brain penetration of potential CNS therapeutics. Effective extrusion from the brain by transporters is a frequent reason for the pharmaceutical industry to exclude novel compounds from further development for CNS therapeutics. Moreover, high transporter expression levels that are present in individual patients or may be generally associated with the pathophysiology seem to be a major cause of therapeutic failure in a variety of CNS diseases including brain tumors, epilepsy, brain HIV infection, and psychiatric disorders. Increasing knowledge of the structure and function of the blood-brain barrier creates a basis for the development of strategies which aim to enhance brain uptake of beneficial pharmaceutical compounds. The different strategies discussed in this review aim to modulate blood-brain barrier function or to bypass constituents of the blood-brain barrier.

The Contribution of Art Therapy to the Dissociative Disorders.

ERIC Educational Resources Information Center

Murphy, Patricia S.

1994-01-01

Explored concepts of brain hemispheric lateralization and distinct right brain functioning in extensive dissociation by administering Dissociative Experiences Scale to 114 engineering students and 92 university drawing students. Chi-square calculation found differences in dissociative scoring levels between groups that approached significance at…

The promises and pitfalls of applying computational models to neurological and psychiatric disorders.

PubMed

Teufel, Christoph; Fletcher, Paul C

2016-10-01

Computational models have become an integral part of basic neuroscience and have facilitated some of the major advances in the field. More recently, such models have also been applied to the understanding of disruptions in brain function. In this review, using examples and a simple analogy, we discuss the potential for computational models to inform our understanding of brain function and dysfunction. We argue that they may provide, in unprecedented detail, an understanding of the neurobiological and mental basis of brain disorders and that such insights will be key to progress in diagnosis and treatment. However, there are also potential problems attending this approach. We highlight these and identify simple principles that should always govern the use of computational models in clinical neuroscience, noting especially the importance of a clear specification of a model's purpose and of the mapping between mathematical concepts and reality. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Altered spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder: A resting-state fMRI study.

PubMed

Zhu, Xi; He, Zhongqiong; Luo, Cheng; Qiu, Xiangmiao; He, Shixu; Peng, Anjiao; Zhang, Lin; Chen, Lei

2018-03-15

To investigate alterations in spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder using resting-state functional magnetic resonance imaging (RS-fMRI). Eighteen MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder (PDD), 17 MRI-negative refractory temporal lobe epilepsy patients without major depressive disorder (nPDD), and 21 matched healthy controls (HC) were recruited from West China Hospital of SiChuan University from April 2016 to June 2017. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 17-item Hamilton Depression Rating Scale were employed to confirm the diagnosis of major depressive disorder and assess the severity of depression. All participants underwent RS-fMRI scans using a 3.0T MRI system. MRI data were compared and analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) to measure spontaneous brain activity. These two methods were both used to evaluate spontaneous cerebral activity. The PDD group showed significantly altered spontaneous brain activity in the bilateral mesial prefrontal cortex, precuneus, angular gyrus, right parahippocampal gyrus, and right temporal pole. Meanwhile, compared with HC, the nPDD group demonstrated altered spontaneous brain activity in the temporal neocortex but no changes in mesial temporal structures. The PDD group showed regional brain activity alterations in the prefrontal-limbic system and dysfunction of the default mode network. The underlying pathophysiology of PDD may be provided for further studies. Copyright © 2018 Elsevier B.V. All rights reserved.

Pharmacomodulation of microRNA Expression in Neurocognitive Diseases: Obstacles and Future Opportunities.

PubMed

Simion, Viorel; Nadim, Wissem Deraredj; Benedetti, Helene; Pichon, Chantal; Morisset-Lopez, Severine; Baril, Patrick

2017-01-01

Given the importance of microRNAs (miRNAs) in modulating brain functions and their implications in neurocognitive disorders there are currently significant efforts devoted in the field of miRNA-based therapeutics to correct and/or to treat these brain diseases. The observation that miRNA 29a/b-1 cluster, miRNA 10b and miRNA 7, for instance, are frequently deregulated in the brains of patients with neurocognitive diseases and in animal models of Alzheimer, Huntington's and Parkinson's diseases, suggest that correction of miRNA expression using agonist or antagonist miRNA oligonucleotides might be a promising approach to correct or even to cure such diseases. The encouraging results from recent clinical trials allow envisioning that pharmacological approaches based on miRNAs might, in a near future, reach the requirements for successful therapeutic outcomes and will improve the healthcare of patients with brain injuries or disorders. This review will focus on the current strategies used to modulate pharmacological function of miRNA using chemically modified oligonucleotides. We will then review the recent literature on strategies to improve nucleic acid delivery across the blood-brain barrier which remains a severe obstacle to the widespread application of miRNA therapeutics to treat brain diseases. Finally, we provide a state-of-art of current preclinical research performed in animal models for the treatment of neurocognitive disorders using miRNA as therapeutic agents and discuss future developments of miRNA therapeutics.

Pharmacomodulation of microRNA Expression in Neurocognitive Diseases: Obstacles and Future Opportunities

PubMed Central

Simion, Viorel; Nadim, Wissem Deraredj; Benedetti, Hélène; Pichon, Chantal; Morisset-Lopez, Severine; Baril, Patrick

2017-01-01

Given the importance of microRNAs (miRNAs) in modulating brain functions and their implications in neurocognitive disorders there are currently significant efforts devoted in the field of miRNA-based therapeutics to correct and/or to treat these brain diseases. The observation that miRNA 29a/b-1 cluster, miRNA 10b and miRNA 7, for instance, are frequently deregulated in the brains of patients with neurocognitive diseases and in animal models of Alzheimer, Huntington’s and Parkinson’s diseases, suggest that correction of miRNA expression using agonist or antagonist miRNA oligonucleotides might be a promising approach to correct or even to cure such diseases. The encouraging results from recent clinical trials allow envisioning that pharmacological approaches based on miRNAs might, in a near future, reach the requirements for successful therapeutic outcomes and will improve the healthcare of patients with brain injuries or disorders. This review will focus on the current strategies used to modulate pharmacological function of miRNA using chemically modified oligonucleotides. We will then review the recent literature on strategies to improve nucleic acid delivery across the blood-brain barrier which remains a severe obstacle to the widespread application of miRNA therapeutics to treat brain diseases. Finally, we provide a state-of-art of current preclinical research performed in animal models for the treatment of neurocognitive disorders using miRNA as therapeutic agents and discuss future developments of miRNA therapeutics. PMID:27397479

Disorder-specific functional abnormalities during temporal discounting in youth with Attention Deficit Hyperactivity Disorder (ADHD), Autism and comorbid ADHD and Autism.

PubMed

Chantiluke, Kaylita; Christakou, Anastasia; Murphy, Clodagh M; Giampietro, Vincent; Daly, Eileen M; Ecker, Christina; Brammer, Michael; Murphy, Declan G; Rubia, Katya

2014-08-30

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share cognitive abnormalities in temporal foresight. A key question is whether shared cognitive phenotypes are based on common or different underlying pathophysiologies and whether comorbid patients have additive neurofunctional deficits, resemble one of the disorders or have a different pathophysiology. We compared age- and IQ-matched boys with non-comorbid ADHD (18), non-comorbid ASD (15), comorbid ADHD and ASD (13) and healthy controls (18) using functional magnetic resonance imaging (fMRI) during a temporal discounting task. Only the ASD and the comorbid groups discounted delayed rewards more steeply. The fMRI data showed both shared and disorder-specific abnormalities in the three groups relative to controls in their brain-behaviour associations. The comorbid group showed both unique and more severe brain-discounting associations than controls and the non-comorbid patient groups in temporal discounting areas of ventromedial and lateral prefrontal cortex, ventral striatum and anterior cingulate, suggesting that comorbidity is neither an endophenocopy of the two pure disorders nor an additive pathology. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

A human brain network derived from coma-causing brainstem lesions.

PubMed

Fischer, David B; Boes, Aaron D; Demertzi, Athena; Evrard, Henry C; Laureys, Steven; Edlow, Brian L; Liu, Hesheng; Saper, Clifford B; Pascual-Leone, Alvaro; Fox, Michael D; Geerling, Joel C

2016-12-06

To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. © 2016 American Academy of Neurology.

A human brain network derived from coma-causing brainstem lesions

PubMed Central

Boes, Aaron D.; Demertzi, Athena; Evrard, Henry C.; Laureys, Steven; Edlow, Brian L.; Liu, Hesheng; Saper, Clifford B.; Pascual-Leone, Alvaro; Geerling, Joel C.

2016-01-01

Objective: To characterize a brainstem location specific to coma-causing lesions, and its functional connectivity network. Methods: We compared 12 coma-causing brainstem lesions to 24 control brainstem lesions using voxel-based lesion-symptom mapping in a case-control design to identify a site significantly associated with coma. We next used resting-state functional connectivity from a healthy cohort to identify a network of regions functionally connected to this brainstem site. We further investigated the cortical regions of this network by comparing their spatial topography to that of known networks and by evaluating their functional connectivity in patients with disorders of consciousness. Results: A small region in the rostral dorsolateral pontine tegmentum was significantly associated with coma-causing lesions. In healthy adults, this brainstem site was functionally connected to the ventral anterior insula (AI) and pregenual anterior cingulate cortex (pACC). These cortical areas aligned poorly with previously defined resting-state networks, better matching the distribution of von Economo neurons. Finally, connectivity between the AI and pACC was disrupted in patients with disorders of consciousness, and to a greater degree than other brain networks. Conclusions: Injury to a small region in the pontine tegmentum is significantly associated with coma. This brainstem site is functionally connected to 2 cortical regions, the AI and pACC, which become disconnected in disorders of consciousness. This network of brain regions may have a role in the maintenance of human consciousness. PMID:27815400

Communication in autism spectrum disorder: a guide for pediatric nurses.

PubMed

Brown, Amanda B; Elder, Jennifer H

2014-01-01

In the United States, one in every 68 children has autism spectrum disorder (ASD) (Centers for Disease Control and Prevention, 2014). ASD is a developmental disorder of the brain that is characterized by impairments in social interaction, communication, and repetitive patterns of behavior (American Psychiatric Association [APA], 2013). Nurses have a duty to provide high quality care to children with ASD. Effective communication is essential to providing quality care. Three main theories attempt to explain how the ASD brain functions and the implications on communication: lack of theory of mind, weak central coherence, and lack of executive function. Children with ASD have difficulties in vocalic, kinesthetic, and proxemic aspects of communication (Notbhom, 2006). Simple adaptations to environment and style can make the communication between nurses and children with ASD easier and more effective (Aylott, 2000; Green et al., 2010).

Neural correlates of strategic processes underlying episodic memory in women with major depression: A 15O-PET study.

PubMed

Ottowitz, William E; Deckersbach, Thilo; Savage, Cary R; Lindquist, Martin A; Dougherty, Darin D

2010-01-01

To evaluate the functional integrity of brain regions underlying strategic mnemonic processing in patients with major depressive disorder, the authors administered a modified version of the California Verbal Learning Test to depressed patients during presentation of lists of unrelated words and, conversely, during presentation of lists of related words with and without orientation regarding the relatedness of the words (eight healthy females, IQ=122, and eight depressed females, IQ=107). Brain function evaluated across all three conditions showed that patients with major depressive disorder revealed activation of the right anterior cingulate cortex, left ventrolateral prefrontal cortex, both hippocampi, and the left orbitofrontal cortex. Further analysis showed that patients with major depressive disorder had greater activation of the right anterior cingulate cortex during semantic organization and the right ventrolateral prefrontal cortex during strategy initiation.

[CHARACTERIZATION OF VESTIBULAR DISORDERS IN THE INJURED PERSONS WITH THE BRAIN CONCUSSION IN ACUTE PERIOD].

PubMed

Skobska, O E; Kadzhaya, N V; Andreyev, O A; Potapov, E V

2015-04-01

There were examined 32 injured persons, ageing (34.1 ± 1.3) yrs at average, for the brain commotion (BC). The adopted protocol SCAT-3 (Standardized Concussion Assessment Tool, 3rd ed.), DHI (Dizziness Handicap Inventory questionnaire), computer stabilography (KS) were applied for the vestibular disorders diagnosis. There was established, that in acute period of BC a dyssociation between regression of objective neurological symptoms and permanence of the BC indices occurs, what confirms a latent disorder of the balance function. Changes of basic indices of statokinesiography, including increase of the vibration amplitude enhancement in general centre of pressure in a saggital square and the BC square (235.3 ± 13.7) mm2 in a modified functional test of Romberg with the closed eyes is possible to apply as objective criteria for the BC diagnosis.

Combining Fiber Dissection, Plastination, and Tractography for Neuroanatomical Education: Revealing the Cerebellar Nuclei and Their White Matter Connections

ERIC Educational Resources Information Center

Arnts, Hisse; Kleinnijenhuis, Michiel; Kooloos, Jan G. M.; Schepens-Franke, Annelieke N.; van Cappellen van Walsum, Anne-Marie

2014-01-01

In recent years, there has been a growing interest in white matter anatomy of the human brain. With advances in brain imaging techniques, the significance of white matter integrity for brain function has been demonstrated in various neurological and psychiatric disorders. As the demand for interpretation of clinical and imaging data on white…

Functional connectivity in the mouse brain imaged by B-mode photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Nasiriavanaki, Mohammadreza; Xing, Wenxin; Xia, Jun; Wang, Lihong V.

2014-03-01

The increasing use of mouse models for human brain disease studies, coupled with the fact that existing functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing acoustic-resolution photoacoustic microscopy (AR-PAM), we imaged spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images were acquired noninvasively in B-scan mode with a fast frame rate, a large field of view, and a high spatial resolution. At a location relative to the bregma 0, correlations were investigated inter-hemispherically between bilaterally homologous regions, as well as intra-hemispherically within the same functional regions. The functional connectivity in different functional regions was studied. The locations of these regions agreed well with the Paxinos mouse brain atlas. The functional connectivity map obtained in this study can then be used in the investigation of brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy. Our experiments show that photoacoustic microscopy is capable to detect connectivities between different functional regions in B-scan mode, promising a powerful functional imaging modality for future brain research.

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2012 CFR

2012-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2011 CFR

2011-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

16 CFR 1303.5 - Findings.

Code of Federal Regulations, 2014 CFR

2014-01-01

... designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability, withdrawal... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

Developing a clinical translational neuroscience taxonomy for anxiety and mood disorder: protocol for the baseline-follow up Research domain criteria Anxiety and Depression ("RAD") project.

PubMed

Williams, Leanne M; Goldstein-Piekarski, Andrea N; Chowdhry, Nowreen; Grisanzio, Katherine A; Haug, Nancy A; Samara, Zoe; Etkin, Amit; O'Hara, Ruth; Schatzberg, Alan F; Suppes, Trisha; Yesavage, Jerome

2016-03-15

Understanding how brain circuit dysfunctions relate to specific symptoms offers promise for developing a brain-based taxonomy for classifying psychopathology, identifying targets for mechanistic studies and ultimately for guiding treatment choice. The goal of the Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health is to accelerate the development of such neurobiological models of mental disorder independent of traditional diagnostic criteria. In our RDoC Anxiety and Depression ("RAD") project we focus trans-diagnostically on the spectrum of depression and anxiety psychopathology. Our aims are a) to use brain imaging to define cohesive dimensions defined by dysfunction of circuits involved in reactivity to and regulation of negatively valenced emotional stimulation and in cognitive control, b) to assess the relationships between these dimension and specific symptoms, behavioral performance and the real world capacity to function socially and at work and c) to assess the stability of brain-symptom-behavior-function relationships over time. Here we present the protocol for the "RAD" project, one of the first RDoC studies to use brain circuit functioning to define new dimensions of psychopathology. The RAD project follows baseline-follow up design. In line with RDoC principles we use a strategy for recruiting all clients who "walk through the door" of a large community mental health clinic as well as the surrounding community. The clinic attends to a broad spectrum of anxiety and mood-related symptoms. Participants are unmedicated and studied at baseline using a standardized battery of functional brain imaging, structural brain imaging and behavioral probes that assay constructs of threat reactivity, threat regulation and cognitive control. The battery also includes self-report measures of anxiety and mood symptoms, and social and occupational functioning. After baseline assessments, therapists in the clinic apply treatment planning as usual. Follow-up assessments are undertaken at 3 months, to establish the reliability of brain-based subgroups over time and to assess whether these subgroups predict real-world functional capacity over time. First enrollment was August 2013, and is ongoing. This project is designed to advance knowledge toward a neural circuit taxonomy for mental disorder. Data will be shared via the RDoC database for dissemination to the scientific community. The clinical translational neuroscience goals of the project are to develop brain-behavior profile reports for each individual participant and to refine these reports with therapist feedback. Reporting of results is expected from December 2016 onward. ClinicalTrials.gov Identifier: NCT02220309 . Registered: August 13, 2014.

Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy.

PubMed

Shamseldin, Hanan E; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S; Gleeson, Joseph G; Alkuraya, Fowzan S

2016-01-07

Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Brain activation patterns in women with acquired hypoactive sexual desire disorder and women with normal sexual function: a cross-sectional pilot study.

PubMed

Woodard, Terri L; Nowak, Nicole T; Balon, Richard; Tancer, Manuel; Diamond, Michael P

2013-10-01

To examine and compare brain activation patterns of premenopausal women with normal sexual function and those with hypoactive sexual desire disorder (HSDD) during viewing of validated sexually explicit film clips. Cross-sectional pilot study. University-based clinical research center. Premenopausal women. None. Areas of brain activation during viewing of sexually explicit film clips. Women with normal sexual function showed significantly greater activation of the right thalamus, left insula, left precentral gyrus, and left parahippocampal gyrus in comparison with women with HSDD, who exhibited greater activation of the right medial frontal gyrus and left precuneus regions. Women with HSDD may have alterations in activation of limbic and cortical structures responsible for acquiring, encoding, and retrieving memory, the processing and memory of emotional reactions, and areas responsible for heightened attention to one's own physical state. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Brain activation patterns in women with acquired hypoactive sexual desire disorder and women with normal sexual function: a cross-sectional pilot study

PubMed Central

Woodard, Terri L.; Nowak, Nicole T.; Balon, Richard; Tancer, Manuel; Diamond, Michael P.

2013-01-01

Objective To examine and compare brain activation patterns of premenopausal women with normal sexual function and those with hypoactive sexual desire disorder (HSDD) during viewing of validated sexually explicit film clips. Design Cross-sectional pilot study. Setting University-based clinical research center. Patient(s) Premenopausal women. Intervention(s) None. Main Outcome Measure(s) Areas of brain activation during viewing of sexually explicit film clips. Result(s) Women with normal sexual function showed significantly greater activation of the right thalamus, left insula, left precentral gyrus, and left parahippocampal gyrus in comparison with women with HSDD, who exhibited greater activation of the right medial frontal gyrus and left precuneus regions. Conclusion(s) Women with HSDD may have alterations in activation of limbic and cortical structures responsible for acquiring, encoding, and retrieving memory, the processing and memory of emotional reactions, and areas responsible for heightened attention to one’s own physical state. PMID:23830149

Advances in the understanding of headache.

PubMed

Goadsby, Peter J

2005-01-01

Primary headache disorders account for a substantial part of the morbidity seen in medical practice and so advances in their understanding and management are of general importance. The classification of headache disorders has recently been revised, and the importance of frequent migraine, chronic (transformed) migraine and some important, albeit rarer, conditions that were previously not included has been recognized. Identification of the first genes for a migraine syndrome, namely familial hemiplegic migraine, and their classification as channelopathies opens up new understanding of these disorders and their possible pathophysiology. Functional brain imaging of migraine and cluster headache has placed the pathophysiology of these disorders firmly and clearly in the brain. As our understanding of migraine and related syndromes has increased, new therapies have been developed which reduce the significant disability associated with these important neurological disorders.

Characteristics of allelic gene expression in human brain cells from single-cell RNA-seq data analysis.

PubMed

Zhao, Dejian; Lin, Mingyan; Pedrosa, Erika; Lachman, Herbert M; Zheng, Deyou

2017-11-10

Monoallelic expression of autosomal genes has been implicated in human psychiatric disorders. However, there is a paucity of allelic expression studies in human brain cells at the single cell and genome wide levels. In this report, we reanalyzed a previously published single-cell RNA-seq dataset from several postmortem human brains and observed pervasive monoallelic expression in individual cells, largely in a random manner. Examining single nucleotide variants with a predicted functional disruption, we found that the "damaged" alleles were overall expressed in fewer brain cells than their counterparts, and at a lower level in cells where their expression was detected. We also identified many brain cell type-specific monoallelically expressed genes. Interestingly, many of these cell type-specific monoallelically expressed genes were enriched for functions important for those brain cell types. In addition, function analysis showed that genes displaying monoallelic expression and correlated expression across neuronal cells from different individual brains were implicated in the regulation of synaptic function. Our findings suggest that monoallelic gene expression is prevalent in human brain cells, which may play a role in generating cellular identity and neuronal diversity and thus increasing the complexity and diversity of brain cell functions.

Quantitative analysis of diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) for brain disorders

NASA Astrophysics Data System (ADS)

Lee, Jae-Seung; Im, In-Chul; Kang, Su-Man; Goo, Eun-Hoe; Kwak, Byung-Joon

2013-07-01

This study aimed to quantitatively analyze data from diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) in patients with brain disorders and to assess its potential utility for analyzing brain function. DTI was obtained by performing 3.0-T magnetic resonance imaging for patients with Alzheimer's disease (AD) and vascular dementia (VD), and the data were analyzed using Matlab-based SPM software. The two-sample t-test was used for error analysis of the location of the activated pixels. We compared regions of white matter where the fractional anisotropy (FA) values were low and the apparent diffusion coefficients (ADCs) were increased. In the AD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right sub-lobar insula, and right occipital lingual gyrus whereas the ADCs were significantly increased in the right inferior frontal gyrus and right middle frontal gyrus. In the VD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right limbic cingulate gyrus, and right sub-lobar caudate tail whereas the ADCs were significantly increased in the left lateral globus pallidus and left medial globus pallidus. In conclusion by using DTI and SPM analysis, we were able to not only determine the structural state of the regions affected by brain disorders but also quantitatively analyze and assess brain function.

Frequency-specific alterations in functional connectivity in treatment-resistant and -sensitive major depressive disorder.

PubMed

He, Zongling; Cui, Qian; Zheng, Junjie; Duan, Xujun; Pang, Yajing; Gao, Qing; Han, Shaoqiang; Long, Zhiliang; Wang, Yifeng; Li, Jiao; Wang, Xiao; Zhao, Jingping; Chen, Huafu

2016-11-01

Major depressive disorder (MDD) may involve alterations in brain functional connectivity in multiple neural circuits and present large-scale network dysfunction. Patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) show different responses to antidepressants and aberrant brain functions. This study aims to investigate functional connectivity patterns of TRD and TSD at the whole brain resting state. Seventeen patients with TRD, 17 patients with TSD, and 17 healthy controls matched with age, gender, and years of education were recruited in this study. The brain was divided using an automated anatomical labeling atlas into 90 regions of interest, which were used to construct the entire brain functional networks. An analysis method called network-based statistic was used to explore the dysconnected subnetworks of TRD and TSD at different frequency bands. At resting state, TSD and TRD present characteristic patterns of network dysfunction at special frequency bands. The dysconnected subnetwork of TSD mainly lies in the fronto-parietal top-down control network. Moreover, the abnormal neural circuits of TRD are extensive and complex. These circuits not only depend on the abnormal affective network but also involve other networks, including salience network, auditory network, visual network, and language processing cortex. Our findings reflect that the pathological mechanism of TSD may refer to impairment in cognitive control, whereas TRD mainly triggers the dysfunction of emotion processing and affective cognition. This study reveals that differences in brain functional connectivity at resting state reflect distinct pathophysiological mechanisms in TSD and TRD. These findings may be helpful in differentiating two types of MDD and predicting treatment responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Different Aberrant Mentalizing Networks in Males and Females with Autism Spectrum Disorders: Evidence from Resting-State Functional Magnetic Resonance Imaging

ERIC Educational Resources Information Center

Yang, Jie; Lee, Jonathan

2018-01-01

Previous studies have found that individuals with autism spectrum disorders show impairments in mentalizing processes and aberrant brain activity compared with typically developing participants. However, the findings are mainly from male participants and the aberrant effects in autism spectrum disorder females and sex differences are still…

White Matter Compromise of Callosal and Subcortical Fiber Tracts in Children with Autism Spectrum Disorder: A Diffusion Tensor Imaging Study

ERIC Educational Resources Information Center

Shukla, Dinesh K.; Keehn, Brandon; Lincoln, Alan J.; Muller, Ralph-Axel

2010-01-01

Objective: Autism spectrum disorder (ASD) is increasingly viewed as a disorder of functional networks, highlighting the importance of investigating white matter and interregional connectivity. We used diffusion tensor imaging (DTI) to examine white matter integrity for the whole brain and for corpus callosum, internal capsule, and middle…

Artistic creativity, style and brain disorders.

PubMed

Bogousslavsky, Julien

2005-01-01

The production of novel, motivated or useful material defines creativity, which appears to be one of the higher, specific, human brain functions. While creativity can express itself in virtually any domain, art might particularly well illustrate how creativity may be modulated by the normal or pathological brain. Evidence emphasizes global brain functioning in artistic creativity and output, but critical steps which link perception processing to execution of a work, such as extraction-abstraction, as well as major developments of non-esthetic values attached to art also underline complex activation and inhibition processes mainly localized in the frontal lobe. Neurological diseases in artists provide a unique opportunity to study brain-creativity relationships, in particular through the stylistic changes which may develop after brain lesion. (c) 2005 S. Karger AG, Basel

Resting State Network Topology of the Ferret Brain

PubMed Central

Zhou, Zhe Charles; Salzwedel, Andrew P.; Radtke-Schuller, Susanne; Li, Yuhui; Sellers, Kristin K.; Gilmore, John H.; Shih, Yen-Yu Ian; Fröhlich, Flavio; Gao, Wei

2016-01-01

Resting state functional magnetic resonance imaging (rsfMRI) has emerged as a versatile tool for non-invasive measurement of functional connectivity patterns in the brain. RsfMRI brain dynamics in rodents, non-human primates, and humans share similar properties; however, little is known about the resting state functional connectivity patterns in the ferret, an animal model with high potential for developmental and cognitive translational study. To address this knowledge-gap, we performed rsfMRI on anesthetized ferrets using a 9.4 tesla MRI scanner, and subsequently performed group-level independent component analysis (gICA) to identify functionally connected brain networks. Group-level ICA analysis revealed distributed sensory, motor, and higher-order networks in the ferret brain. Subsequent connectivity analysis showed interconnected higher-order networks that constituted a putative default mode network (DMN), a network that exhibits altered connectivity in neuropsychiatric disorders. Finally, we assessed ferret brain topological efficiency using graph theory analysis and found that the ferret brain exhibits small-world properties. Overall, these results provide additional evidence for pan-species resting-state networks, further supporting ferret-based studies of sensory and cognitive function. PMID:27596024

Single Subject Prediction of Brain Disorders in Neuroimaging: Promises and Pitfalls

PubMed Central

Arbabshirani, Mohammad R.; Plis, Sergey; Sui, Jing; Calhoun, Vince D.

2016-01-01

Neuroimaging-based single subject prediction of brain disorders has gained increasing attention in recent years. Using a variety of neuroimaging modalities such as structural, functional and diffusion MRI, along with machine learning techniques, hundreds of studies have been carried out for accurate classification of patients with heterogeneous mental and neurodegenerative disorders such as schizophrenia and Alzheimer's disease. More than 500 studies have been published during the past quarter century on single subject prediction focused on a multiple brain disorders. In the first part of this study, we provide a survey of more than 200 reports in this field with a focus on schizophrenia, mild cognitive impairment (MCI), Alzheimer's disease (AD), depressive disorders, autism spectrum disease (ASD) and attention-deficit hyperactivity disorder (ADHD). Detailed information about those studies such as sample size, type and number of extracted features and reported accuracy are summarized and discussed. To our knowledge, this is by far the most comprehensive review of neuroimaging-based single subject prediction of brain disorders. In the second part, we present our opinion on major pitfalls of those studies from a machine learning point of view. Common biases are discussed and suggestions are provided. Moreover, emerging trends such as decentralized data sharing, multimodal brain imaging, differential diagnosis, disease subtype classification and deep learning are also discussed. Based on this survey, there are extensive evidences showing the great potential of neuroimaging data for single subject prediction of various disorders. However, the main bottleneck of this exciting field is still the limited sample size, which could be potentially addressed by modern data sharing models such as the ones discussed in this paper. Emerging big data technologies and advanced data-intensive machine learning methodologies such as deep learning have coincided with an increasing need for accurate, robust and generalizable single subject prediction of brain disorders during an exciting time. In this report, we survey the past and offer some opinions regarding the road ahead. PMID:27012503

Single subject prediction of brain disorders in neuroimaging: Promises and pitfalls.

PubMed

Arbabshirani, Mohammad R; Plis, Sergey; Sui, Jing; Calhoun, Vince D

2017-01-15

Neuroimaging-based single subject prediction of brain disorders has gained increasing attention in recent years. Using a variety of neuroimaging modalities such as structural, functional and diffusion MRI, along with machine learning techniques, hundreds of studies have been carried out for accurate classification of patients with heterogeneous mental and neurodegenerative disorders such as schizophrenia and Alzheimer's disease. More than 500 studies have been published during the past quarter century on single subject prediction focused on a multiple brain disorders. In the first part of this study, we provide a survey of more than 200 reports in this field with a focus on schizophrenia, mild cognitive impairment (MCI), Alzheimer's disease (AD), depressive disorders, autism spectrum disease (ASD) and attention-deficit hyperactivity disorder (ADHD). Detailed information about those studies such as sample size, type and number of extracted features and reported accuracy are summarized and discussed. To our knowledge, this is by far the most comprehensive review of neuroimaging-based single subject prediction of brain disorders. In the second part, we present our opinion on major pitfalls of those studies from a machine learning point of view. Common biases are discussed and suggestions are provided. Moreover, emerging trends such as decentralized data sharing, multimodal brain imaging, differential diagnosis, disease subtype classification and deep learning are also discussed. Based on this survey, there is extensive evidence showing the great potential of neuroimaging data for single subject prediction of various disorders. However, the main bottleneck of this exciting field is still the limited sample size, which could be potentially addressed by modern data sharing models such as the ones discussed in this paper. Emerging big data technologies and advanced data-intensive machine learning methodologies such as deep learning have coincided with an increasing need for accurate, robust and generalizable single subject prediction of brain disorders during an exciting time. In this report, we survey the past and offer some opinions regarding the road ahead. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of brain-wide connectivity architecture in awake rats.

PubMed

Ma, Zilu; Ma, Yuncong; Zhang, Nanyin

2018-08-01

Childhood and adolescence are both critical developmental periods, evidenced by complex neurophysiological changes the brain undergoes and high occurrence rates of neuropsychiatric disorders during these periods. Despite substantial progress in elucidating the developmental trajectories of individual neural circuits, our knowledge of developmental changes of whole-brain connectivity architecture in animals is sparse. To fill this gap, here we longitudinally acquired rsfMRI data in awake rats during five developmental stages from juvenile to adulthood. We found that the maturation timelines of brain circuits were heterogeneous and system specific. Functional connectivity (FC) tended to decrease in subcortical circuits, but increase in cortical circuits during development. In addition, the developing brain exhibited hemispheric functional specialization, evidenced by reduced inter-hemispheric FC between homotopic regions, and lower similarity of region-to-region FC patterns between the two hemispheres. Finally, we showed that whole-brain network development was characterized by reduced clustering (i.e. local communication) but increased integration (distant communication). Taken together, the present study has systematically characterized the development of brain-wide connectivity architecture from juvenile to adulthood in awake rats. It also serves as a critical reference point for understanding circuit- and network-level changes in animal models of brain development-related disorders. Furthermore, FC data during brain development in awake rodents contain high translational value and can shed light onto comparative neuroanatomy. Copyright © 2018 Elsevier Inc. All rights reserved.

Between destiny and disease: genetics and molecular pathways of human central nervous system aging.

PubMed

Glorioso, Christin; Sibille, Etienne

2011-02-01

Aging of the human brain is associated with "normal" functional, structural, and molecular changes that underlie alterations in cognition, memory, mood and motor function, amongst other processes. Normal aging also imposes a robust constraint on the onset of many neurological diseases, ranging from late onset neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's diseases (PD), to early onset psychiatric disorders, such as bipolar disorder (BPD) and schizophrenia (SCZ). The molecular mechanisms and genetic underpinnings of age-related changes in the brain are understudied, and, while they share some overlap with peripheral mechanisms of aging, many are unique to the largely non-mitotic brain. Hence, understanding mechanisms of brain aging and identifying associated modulators may have profound consequences for the prevention and treatment of age-related impairments and diseases. Here we review current knowledge on age-related functional and structural changes, their molecular and genetic underpinnings, and discuss how these pathways may contribute to the vulnerability to develop age-related neurological diseases. We highlight recent findings from human post-mortem brain microarray studies, which we hypothesize, point to a potential genetically controlled transcriptional program underlying molecular changes and age-gating of neurological diseases. Finally, we discuss the implications of this model for understanding basic mechanisms of brain aging and for the future investigation of therapeutic approaches. Copyright © 2010 Elsevier Ltd. All rights reserved.

A greater focus on metals in biomedicine and neuroscience is needed.

PubMed

White, Anthony R

2016-11-05

Metals have many essential functions in the brain and a large body of evidence supports important roles for altered metal stasis in many brain disorders. However, despite this evidence, acceptance of metals as key mediators of brain dysfunction is largely lacking in mainstream biomedicine. This editorial will outline the possible reasons for this and suggest potential means to improve the acceptance of metals as central players in brain disease.

Evidence of native α-synuclein conformers in the human brain.

PubMed

Gould, Neal; Mor, Danielle E; Lightfoot, Richard; Malkus, Kristen; Giasson, Benoit; Ischiropoulos, Harry

2014-03-14

α-Synuclein aggregation is central to the pathogenesis of several brain disorders. However, the native conformations and functions of this protein in the human brain are not precisely known. The native state of α-synuclein was probed by gel filtration coupled with native gradient gel separation, an array of antibodies with non-overlapping epitopes, and mass spectrometry. The existence of metastable conformers and stable monomer was revealed in the human brain.

What is the role of brain mechanisms underlying arousal in recovery of motor function after structural brain injuries?

PubMed Central

Schiff, Nicholas D.

2013-01-01

Purpose of review Standard neurorehabilitation approaches have limited impact on motor recovery in patients with severe injuries. Consideration of the contributions of impaired arousal offers a novel approach to understand and enhance recovery. Recent findings Animal and human neuroimaging studies are elucidating the neuroanatomical bases of arousal and of arousal regulation, the process by which the cerebrum mobilizes resources. Studies of patients with disorders of consciousness have revealed that recovery of these processes is associated with marked improvements in motor performance. Recent studies have also demonstrated that patients with less severe brain injuries also have impaired arousal, manifesting as diminished sustained attention, fatigue and apathy. In these less severely injured patients it is difficult to connect disorders of arousal with motor recovery due to a lack of measures of arousal independent of motor function. Summary Arousal impairment is common after brain injury and likely plays a significant role in recovery of motor function. A more detailed understanding of this connection will help to develop new therapeutic strategies applicable for a wide range of patients. This requires new tools that continuously and objectively measure arousal in patients with brain injury, to correlate with detailed measures of motor performance and recovery. PMID:22002078

Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders.

PubMed

Sato, Wataru; Toichi, Motomi; Uono, Shota; Kochiyama, Takanori

2012-08-13

Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD). However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD.We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI). Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG), fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG). Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex-MTG-IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI

PubMed Central

Xu, Tingting; Cullen, Kathryn R.; Mueller, Bryon; Schreiner, Mindy W.; Lim, Kelvin O.; Schulz, S. Charles; Parhi, Keshab K.

2016-01-01

Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03–0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03–0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge to the current understanding of functional brain networks in BPD. However, due to limitation of small sample sizes, the results of the current study should be viewed as exploratory and need to be validated on large samples in future works. PMID:26977400

Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI.

PubMed

Xu, Tingting; Cullen, Kathryn R; Mueller, Bryon; Schreiner, Mindy W; Lim, Kelvin O; Schulz, S Charles; Parhi, Keshab K

2016-01-01

Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03-0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03-0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge to the current understanding of functional brain networks in BPD. However, due to limitation of small sample sizes, the results of the current study should be viewed as exploratory and need to be validated on large samples in future works.

Decreased long- and short-range functional connectivity at rest in drug-naive major depressive disorder.

PubMed

Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Xue, Zhimin; Zhao, Jingping

2016-08-01

Abnormal functional connectivity has been observed in major depressive disorder. Anatomical distance may affect functional connectivity in patients with major depressive disorder. However, whether and how anatomical distance affects functional connectivity at rest remains unclear in drug-naive patients with major depressive disorder. Forty-four patients with major depressive disorder, as well as 44 age-, sex- and education-matched healthy controls, underwent resting-state functional magnetic resonance imaging scanning. Regional functional connectivity strength was calculated for each voxel in the whole brain, which was further divided into short- and long-range functional connectivity strength. The patients showed decreased long-range positive functional connectivity strength in the right inferior parietal lobule, as well as decreased short-range positive functional connectivity strength in the right insula and right superior temporal gyrus relative to those of the controls. No significant correlations existed between abnormal functional connectivity strength and the clinical variables of the patients. The findings revealed that anatomical distance decreases long- and short-range functional connectivity strength in patients with major depressive disorder, which may underlie the neurobiology of major depressive disorder. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Abnormal brain activation in excoriation (skin-picking) disorder: evidence from an executive planning fMRI study

PubMed Central

Odlaug, Brian L.; Hampshire, Adam; Chamberlain, Samuel R.; Grant, Jon E.

2016-01-01

Background Excoriation (skin-picking) disorder (SPD) is a relatively common psychiatric condition whose neurobiological basis is unknown. Aims To probe the function of fronto-striatal circuitry in SPD. Method Eighteen participants with SPD and 15 matched healthy controls undertook an executive planning task (Tower of London) during functional magnetic resonance imaging (fMRI). Activation during planning was compared between groups using region of interest and whole-brain permutation cluster approaches. Results The SPD group exhibited significant functional underactivation in a cluster encompassing bilateral dorsal striatum (maximal in right caudate), bilateral anterior cingulate and right medial frontal regions. These abnormalities were, for the most part, outside the dorsal planning network typically activated by executive planning tasks. Conclusions Abnormalities of neural regions involved in habit formation, action monitoring and inhibition appear involved in the pathophysiology of SPD. Implications exist for understanding the basis of excessive grooming and the relationship of SPD with putative obsessive–compulsive spectrum disorders. PMID:26159604

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

PubMed Central

Arloth, Janine; Bogdan, Ryan; Weber, Peter; Frishman, Goar; Menke, Andreas; Wagner, Klaus V.; Balsevich, Georgia; Schmidt, Mathias V.; Karbalai, Nazanin; Czamara, Darina; Altmann, Andre; Trümbach, Dietrich; Wurst, Wolfgang; Mehta, Divya; Uhr, Manfred; Klengel, Torsten; Erhardt, Angelika; Carey, Caitlin E.; Conley, Emily Drabant; Ripke, Stephan; Wray, Naomi R.; Lewis, Cathryn M.; Hamilton, Steven P.; Weissman, Myrna M.; Breen, Gerome; Byrne, Enda M.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Cichon, Sven; Heath, Andrew C.; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A.F.; Martin, Nicholas G.; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M.; Penninx, Brenda P.; Pergadia, Michele L.; Potash, James B.; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J.; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H.; Preisig, Martin; Smoller, Jordan W.; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E.; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R.; Bettecken, Thomas; Binder, Elisabeth B.; Breuer, René; Castro, Victor M.; Churchill, Susanne E.; Coryell, William H.; Craddock, Nick; Craig, Ian W.; Czamara, Darina; De Geus, Eco J.; Degenhardt, Franziska; Farmer, Anne E.; Fava, Maurizio; Frank, Josef; Gainer, Vivian S.; Gallagher, Patience J.; Gordon, Scott D.; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V.; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A.; Kohane, Isaac S.; Kohli, Martin A.; Korszun, Ania; Landen, Mikael; Lawson, William B.; Lewis, Glyn; MacIntyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Middleton, Lefkos; Montgomery, Grant M.; Murphy, Shawn N.; Nauck, Matthias; Nolen, Willem A.; Nyholt, Dale R.; O’Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A.; Schulz, Andrea; Schulze, Thomas G.; Shyn, Stanley I.; Sigurdsson, Engilbert; Slager, Susan L.; Smit, Johannes H.; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J.C.G.; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B.; Willemsen, Gonneke; Zitman, Frans G.; Neale, Benjamin; Daly, Mark; Levinson, Douglas F.; Sullivan, Patrick F.; Ruepp, Andreas; Müller-Myhsok, Bertram; Hariri, Ahmad R.; Binder, Elisabeth B.

2015-01-01

Summary Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain. Video Abstract PMID:26050039

Cannabidiol, neuroprotection and neuropsychiatric disorders.

PubMed

Campos, Alline C; Fogaça, Manoela V; Sonego, Andreza B; Guimarães, Francisco S

2016-10-01

Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa. It has possible therapeutic effects over a broad range of neuropsychiatric disorders. CBD attenuates brain damage associated with neurodegenerative and/or ischemic conditions. It also has positive effects on attenuating psychotic-, anxiety- and depressive-like behaviors. Moreover, CBD affects synaptic plasticity and facilitates neurogenesis. The mechanisms of these effects are still not entirely clear but seem to involve multiple pharmacological targets. In the present review, we summarized the main biochemical and molecular mechanisms that have been associated with the therapeutic effects of CBD, focusing on their relevance to brain function, neuroprotection and neuropsychiatric disorders. Copyright © 2016. Published by Elsevier Ltd.

[Psychogenetic neurological disorders in draft age personnel].

PubMed

Akhmetianov, L A; Ovchinnikov, A V

2012-07-01

The tendency of psychogenetic neurological disorders increases with predominance in young persons being students of high schools, students of military, technical and other lyceum was shown. The origin of diseases are psychotraumas (family, work), stress. Also genetic and hereditary factors take place that are indicative for individual rehabilitation organization. The basics of psychosomatic diseases pathogenesis are the disintegration mechanisms in brain structure activity,the disorders of integrative apparatus which provides the relationship between somatic, emotional and vegetative functions. The confirmation of brain work disintegration is achieved by modern computer diagnostic systems. As psychogenic diseases increase the need in methods of computer electroencephalography, evoked potentials, and rheoencephalography application is more actual.

16 CFR § 1303.5 - Findings.

Code of Federal Regulations, 2013 CFR

2013-01-01

... regulation is designed to eliminate or reduce is lead poisoning in children. The adverse effects of this poisoning in children can cause a range of disorders such as hyperactivity, slowed learning ability... functional disorders which are often included under the heading of minimal brain dysfunction. Studies suggest...

Brain Stimulation in Addiction

PubMed Central

Salling, Michael C; Martinez, Diana

2016-01-01

Localized stimulation of the human brain to treat neuropsychiatric disorders has been in place for over 20 years. Although these methods have been used to a greater extent for mood and movement disorders, recent work has explored brain stimulation methods as potential treatments for addiction. The rationale behind stimulation therapy in addiction involves reestablishing normal brain function in target regions in an effort to dampen addictive behaviors. In this review, we present the rationale and studies investigating brain stimulation in addiction, including transcranial magnetic stimulation, transcranial direct current stimulation, and deep brain stimulation. Overall, these studies indicate that brain stimulation has an acute effect on craving for drugs and alcohol, but few studies have investigated the effect of brain stimulation on actual drug and alcohol use or relapse. Stimulation therapies may achieve their effect through direct or indirect modulation of brain regions involved in addiction, either acutely or through plastic changes in neuronal transmission. Although these mechanisms are not well understood, further identification of the underlying neurobiology of addiction and rigorous evaluation of brain stimulation methods has the potential for unlocking an effective, long-term treatment of addiction. PMID:27240657

A compensatory role for declarative memory in neurodevelopmental disorders.

PubMed

Ullman, Michael T; Pullman, Mariel Y

2015-04-01

Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional in these disorders, and because it can learn and retain numerous types of information, functions, and tasks, this system should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Emotional and cognitive functional imaging of estrogen and progesterone effects in the female human brain: a systematic review.

PubMed

Toffoletto, Simone; Lanzenberger, Rupert; Gingnell, Malin; Sundström-Poromaa, Inger; Comasco, Erika

2014-12-01

Ovarian hormones are pivotal for the physiological maintenance of the brain function as well as its response to environmental stimuli. There is mounting evidence attesting the relevance of endogenous ovarian hormones as well as exogenous estradiol and progesterone for emotional and cognitive processing. The present review systematically summarized current knowledge on sex steroid hormonal modulation of neural substrates of emotion and cognition revealed by functional magnetic resonance imaging (fMRI). Twenty-four studies of healthy naturally cycling and combined oral contraceptives (COC) user women, or women undergoing experimental manipulations, during their reproductive age, were included. Furthermore, six studies of premenstrual dysphoric disorder (PMDD), a hormonally based mood disorder, and three of gender dysphoria (GD), which provides an intriguing opportunity to examine the effect of high-dose cross-sex hormone therapy (CSHT) on brain functioning, were included. Globally, low (early follicular and the entire follicular phase for estrogen and progesterone, respectively) and high (COC, CSHT, late follicular and luteal phase for estrogen; COC, mid- and late-luteal phase for progesterone) hormonal milieu diversely affected the response of several brain regions including the amygdala, anterior cingulate cortex, and inferior frontal gyrus, but their functional recruitment across groups and domains was scattered. The constellation of findings provides initial evidence of the influence of sex steroid hormones on cortical and subcortical regions implicated in emotional and cognitive processing. Further well-powered and multimodal neuroimaging studies will be needed to identify the neural mechanism of functional brain alterations induced by sex steroid hormones. Copyright © 2014 Elsevier Ltd. All rights reserved.

Mitochondria, oligodendrocytes and inflammation in bipolar disorder: evidence from transcriptome studies points to intriguing parallels with multiple sclerosis

PubMed Central

Konradi, Christine; Sillivan, Stephanie E.; Clay, Hayley B.

2011-01-01

Gene expression studies of bipolar disorder (BPD) have shown changes in transcriptome profiles in multiple brain regions. Here we summarize the most consistent findings in the scientific literature, and compare them to data from schizophrenia (SZ) and major depressive disorder (MDD). The transcriptome profiles of all three disorders overlap, making the existence of a BPD-specific profile unlikely. Three groups of functionally related genes are consistently expressed at altered levels in BPD, SZ and MDD. Genes involved in energy metabolism and mitochondrial function are downregulated, genes involved in immune response and inflammation are upregulated, and genes expressed in oligodendrocytes are downregulated. Experimental paradigms for multiple sclerosis demonstrate a tight link between energy metabolism, inflammation and demyelination. These studies also show variabilities in the extent of oligodendrocyte stress, which can vary from a downregulation of oligodendrocyte genes, such as observed in psychiatric disorders, to cell death and brain lesions seen in multiple sclerosis. We conclude that experimental models of multiple sclerosis could be of interest for the research of BPD, SZ and MDD. PMID:21310238

Decreased Axon Caliber Underlies Loss of Fiber Tract Integrity, Disproportional Reductions in White Matter Volume, and Microcephaly in Angelman Syndrome Model Mice

PubMed Central

Judson, Matthew C.; Burette, Alain C.; Shen, Mark D.; Rumple, Ashley M.; Del Cid, Wilmer A.; Paniagua, Beatriz

2017-01-01

Angelman syndrome (AS) is a debilitating neurodevelopmental disorder caused by loss of function of the maternally inherited UBE3A allele. It is currently unclear how the consequences of this genetic insult unfold to impair neurodevelopment. We reasoned that by elucidating the basis of microcephaly in AS, a highly penetrant syndromic feature with early postnatal onset, we would gain new insights into the mechanisms by which maternal UBE3A loss derails neurotypical brain growth and function. Detailed anatomical analysis of both male and female maternal Ube3a-null mice reveals that microcephaly in the AS mouse model is primarily driven by deficits in the growth of white matter tracts, which by adulthood are characterized by densely packed axons of disproportionately small caliber. Our results implicate impaired axon growth in the pathogenesis of AS and identify noninvasive structural neuroimaging as a potentially valuable tool for gauging therapeutic efficacy in the disorder. SIGNIFICANCE STATEMENT People who maternally inherit a deletion or nonfunctional copy of the UBE3A gene develop Angelman syndrome (AS), a severe neurodevelopmental disorder. To better understand how loss of maternal UBE3A function derails brain development, we analyzed brain structure in a maternal Ube3a knock-out mouse model of AS. We report that the volume of white matter (WM) is disproportionately reduced in AS mice, indicating that deficits in WM development are a major factor underlying impaired brain growth and microcephaly in the disorder. Notably, we find that axons within the WM pathways of AS model mice are abnormally small in caliber. This defect is associated with slowed nerve conduction, which could contribute to behavioral deficits in AS, including motor dysfunction. PMID:28663201

Regional Homogeneity

PubMed Central

Jiang, Lili; Zuo, Xi-Nian

2015-01-01

Much effort has been made to understand the organizational principles of human brain function using functional magnetic resonance imaging (fMRI) methods, among which resting-state fMRI (rfMRI) is an increasingly recognized technique for measuring the intrinsic dynamics of the human brain. Functional connectivity (FC) with rfMRI is the most widely used method to describe remote or long-distance relationships in studies of cerebral cortex parcellation, interindividual variability, and brain disorders. In contrast, local or short-distance functional interactions, especially at a scale of millimeters, have rarely been investigated or systematically reviewed like remote FC, although some local FC algorithms have been developed and applied to the discovery of brain-based changes under neuropsychiatric conditions. To fill this gap between remote and local FC studies, this review will (1) briefly survey the history of studies on organizational principles of human brain function; (2) propose local functional homogeneity as a network centrality to characterize multimodal local features of the brain connectome; (3) render a neurobiological perspective on local functional homogeneity by linking its temporal, spatial, and individual variability to information processing, anatomical morphology, and brain development; and (4) discuss its role in performing connectome-wide association studies and identify relevant challenges, and recommend its use in future brain connectomics studies. PMID:26170004

A novel approach to analyzing fMRI and SNP data via parallel independent component analysis

NASA Astrophysics Data System (ADS)

Liu, Jingyu; Pearlson, Godfrey; Calhoun, Vince; Windemuth, Andreas

2007-03-01

There is current interest in understanding genetic influences on brain function in both the healthy and the disordered brain. Parallel independent component analysis, a new method for analyzing multimodal data, is proposed in this paper and applied to functional magnetic resonance imaging (fMRI) and a single nucleotide polymorphism (SNP) array. The method aims to identify the independent components of each modality and the relationship between the two modalities. We analyzed 92 participants, including 29 schizophrenia (SZ) patients, 13 unaffected SZ relatives, and 50 healthy controls. We found a correlation of 0.79 between one fMRI component and one SNP component. The fMRI component consists of activations in cingulate gyrus, multiple frontal gyri, and superior temporal gyrus. The related SNP component is contributed to significantly by 9 SNPs located in sets of genes, including those coding for apolipoprotein A-I, and C-III, malate dehydrogenase 1 and the gamma-aminobutyric acid alpha-2 receptor. A significant difference in the presences of this SNP component is found between the SZ group (SZ patients and their relatives) and the control group. In summary, we constructed a framework to identify the interactions between brain functional and genetic information; our findings provide new insight into understanding genetic influences on brain function in a common mental disorder.

The role of polyhalogenated aromatic hydrocarbons on thyroid hormone disruption and cognitive function: a review.

PubMed

Builee, T L; Hatherill, J R

2004-11-01

Thyroid hormones (TH) are essential to normal brain development, influencing behavior and cognitive function in both adult and children. It is suggested that conditions found in TH abnormalities such as hypothyroidism, hyperthyroidism and generalized resistance to thyroid hormone (GRTH) share symptomatic behavioral impulses found in cases of attention deficit hyperactivity disorder (ADHD) and other cognitive disorders. Disrupters of TH are various and prevalent in the environment. This paper reviews the mechanisms of TH disruption caused by the general class of polyhalogenated aromatic hydrocarbons (PHAH)'s acting as thyroid disrupters (TD). PHAHs influence the hypothalamus-pituitary-thyroid (HPT) axis, as mimicry agents affecting synthesis and secretion of TH. Exposure to PHAH induces liver microsomal enzymes UDP-glucuronosyltransferase (UGT) resulting in accelerated clearance of TH. PHAHs can compromise function of transport and receptor binding proteins such as transthyretin and aryl hydrocarbon receptors (Ahr). Glucose metabolism and catecholamine synthesis are disrupted in the brain by the presence of PHAH. Further, PHAH can alter brain growth and development by perturbing cytoskeletal formation, thereby affecting neuronal migration, elongation and branching. The complex relationships between PHAH and cognitive function are examined in regard to the disruption of T4 regulation in the hypothalamus-pituitary-thyroid axis, blood, brain, neurons, liver and pre and postnatal development.

Microarray analysis of gene expression in the cyclooxygenase knockout mice - a connection to autism spectrum disorder.

PubMed

Rai-Bhogal, Ravneet; Ahmad, Eizaaz; Li, Hongyan; Crawford, Dorota A

2018-03-01

The cellular and molecular events that take place during brain development play an important role in governing function of the mature brain. Lipid-signalling molecules such as prostaglandin E 2 (PGE 2 ) play an important role in healthy brain development. Abnormalities along the COX-PGE 2 signalling pathway due to genetic or environmental causes have been linked to autism spectrum disorder (ASD). This study aims to evaluate the effect of altered COX-PGE 2 signalling on development and function of the prenatal brain using male mice lacking cyclooxygenase-1 and cyclooxygenase-2 (COX-1 -/- and COX-2 -/- ) as potential model systems of ASD. Microarray analysis was used to determine global changes in gene expression during embryonic days 16 (E16) and 19 (E19). Gene Ontology: Biological Process (GO:BP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were implemented to identify affected developmental genes and cellular processes. We found that in both knockouts the brain at E16 had nearly twice as many differentially expressed genes, and affected biological pathways containing various ASD-associated genes important in neuronal function. Interestingly, using GeneMANIA and Cytoscape we also show that the ASD-risk genes identified in both COX-1 -/- and COX-2 -/- models belong to protein-interaction networks important for brain development despite of different cellular localization of these enzymes. Lastly, we identified eight genes that belong to the Wnt signalling pathways exclusively in the COX-2 -/- mice at E16. The level of PKA-phosphorylated β-catenin (S552), a major activator of the Wnt pathway, was increased in this model, suggesting crosstalk between the COX-2-PGE 2 and Wnt pathways during early brain development. Overall, these results provide further molecular insight into the contribution of the COX-PGE 2 pathways to ASD and demonstrate that COX-1 -/- and COX-2 -/- animals might be suitable new model systems for studying the disorders. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The emerging role of Rab GTPases in the pathogenesis of Parkinson's disease.

PubMed

Gao, Yujing; Wilson, Gabrielle R; Stephenson, Sarah E M; Bozaoglu, Kiymet; Farrer, Matthew J; Lockhart, Paul J

2018-02-01

The identification of pathogenic mutations in Ras analog in brain 39B (RAB39B) and Ras analog in brain 32 (RAB32) that cause Parkinson's disease (PD) has highlighted the emerging role of protein trafficking in disease pathogenesis. Ras analog in brain (Rab) Guanosine triphosphatase (GTPase) function as master regulators of membrane trafficking, including vesicle formation, movement along cytoskeletal networks, and membrane fusion. Recent studies have linked Rab GTPases with α-synuclein, Leucine-rich repeat kinase 2, and Vacuolar protein sorting 35, 3 key proteins in PD pathogenesis. In this review, we discuss the various RAB GTPases associated with PD, current progress in the research, and potential future directions. Investigations into the function of RAB GTPases will likely provide significant insight into the etiology of PD and identify novel therapeutic targets for a currently incurable disease. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

A case study of a multiply talented savant with an autism spectrum disorder: neuropsychological functioning and brain morphometry.

PubMed

Wallace, Gregory L; Happé, Francesca; Giedd, Jay N

2009-05-27

Neuropsychological functioning and brain morphometry in a savant (case GW) with an autism spectrum disorder (ASD) and both calendar calculation and artistic skills are quantified and compared with small groups of neurotypical controls. Good memory, mental calculation and visuospatial processing, as well as (implicit) knowledge of calendar structure and 'weak' central coherence characterized the cognitive profile of case GW. Possibly reflecting his savant skills, the superior parietal region of GW's cortex was the only area thicker (while areas such as the superior and medial prefrontal, middle temporal and motor cortices were thinner) than that of a neurotypical control group. Taken from the perspective of learning/practice-based models, skills in domains (e.g. calendars, art, music) that capitalize upon strengths often associated with ASD, such as detail-focused processing, are probably further enhanced through over-learning and massive exposure, and reflected in atypical brain structure.

A case study of a multiply talented savant with an autism spectrum disorder: neuropsychological functioning and brain morphometry

PubMed Central

Wallace, Gregory L.; Happé, Francesca; Giedd, Jay N.

2009-01-01

Neuropsychological functioning and brain morphometry in a savant (case GW) with an autism spectrum disorder (ASD) and both calendar calculation and artistic skills are quantified and compared with small groups of neurotypical controls. Good memory, mental calculation and visuospatial processing, as well as (implicit) knowledge of calendar structure and ‘weak’ central coherence characterized the cognitive profile of case GW. Possibly reflecting his savant skills, the superior parietal region of GW's cortex was the only area thicker (while areas such as the superior and medial prefrontal, middle temporal and motor cortices were thinner) than that of a neurotypical control group. Taken from the perspective of learning/practice-based models, skills in domains (e.g. calendars, art, music) that capitalize upon strengths often associated with ASD, such as detail-focused processing, are probably further enhanced through over-learning and massive exposure, and reflected in atypical brain structure. PMID:19528026

Mindfulness Meditation Training and Self-Referential Processing in Social Anxiety Disorder: Behavioral and Neural Effects

PubMed Central

Goldin, Philippe; Ramel, Wiveka; Gross, James

2014-01-01

This study examined the effects of mindfulness-based stress reduction (MBSR) on the brain-behavior mechanisms of self-referential processing in patients with social anxiety disorder (SAD). Sixteen patients underwent functional magnetic resonance imaging while encoding self-referential, valence, and orthographic features of social trait adjectives. Post-MBSR, 14 patients completed neuroimaging. Compared to baseline, MBSR completers showed (a) increased self-esteem and decreased anxiety, (b) increased positive and decreased negative self-endorsement, (c) increased activity in a brain network related to attention regulation, and (d) reduced activity in brain systems implicated in conceptual-linguistic self-view. MBSR-related changes in maladaptive or distorted social self-view in adults diagnosed with SAD may be related to modulation of conceptual self-processing and attention regulation. Self-referential processing may serve as a functional biobehavioral target to measure the effects of mindfulness training. PMID:25568592

New technologies to investigate the brain-gut axis

PubMed Central

Sharma, Abhishek; Lelic, Dina; Brock, Christina; Paine, Peter; Aziz, Qasim

2009-01-01

Functional gastrointestinal disorders are commonly encountered in clinical practice, and pain is their commonest presenting symptom. In addition, patients with these disorders often demonstrate a heightened sensitivity to experimental visceral stimulation, termed visceral pain hypersensitivity that is likely to be important in their pathophysiology. Knowledge of how the brain processes sensory information from visceral structures is still in its infancy. However, our understanding has been propelled by technological imaging advances such as functional Magnetic Resonance Imaging, Positron Emission Tomography, Magnetoencephalography, and Electroencephalography (EEG). Numerous human studies have non-invasively demonstrated the complexity involved in functional pain processing, and highlighted a number of subcortical and cortical regions involved. This review will focus on the neurophysiological pathways (primary afferents, spinal and supraspinal transmission), brain-imaging techniques and the influence of endogenous and psychological processes in healthy controls and patients suffering from functional gastrointestinal disorders. Special attention will be paid to the newer EEG source analysis techniques. Understanding the phenotypic differences that determine an individual’s response to injurious stimuli could be the key to understanding why some patients develop pain and hyperalgesia in response to inflammation/injury while others do not. For future studies, an integrated approach is required incorporating an individual’s psychological, autonomic, neuroendocrine, neurophysiological, and genetic profile to define phenotypic traits that may be at greater risk of developing sensitised states in response to gut inflammation or injury. PMID:19132768

COMT Val(108/158)Met polymorphism effects on emotional brain function and negativity bias.

PubMed

Williams, Leanne M; Gatt, Justine M; Grieve, Stuart M; Dobson-Stone, Carol; Paul, Robert H; Gordon, Evian; Schofield, Peter R

2010-11-15

Biases toward processing negative versus positive information vary as a function of level of awareness, and are modulated by monoamines. Excessive biases are associated with individual differences in mood and emotional stability, and emotional disorder. Here, we examined the impact of the catechol-O-methyltransferase (COMT) Val(108/158)Met polymorphism, involved in dopamine and norepinephrine catabolism, on both emotional brain function and self-reported negativity bias. COMT genotyping and self-reported level of negativity bias were completed for 46 healthy participants taking part in the Brain Resource International Database. Functional MRI was undertaken during perception of facial expressions of fear and happiness presented under unmasked (consciously identified) and masked (to prevent conscious detection) conditions. Structural MR images were also acquired. A greater number of COMT Met alleles predicted increased activation in brainstem, amygdala, basal ganglia and medial prefrontal regions for conscious fear, but decreased activation for conscious happiness. This pattern was also apparent for brainstem activation for the masked condition. Effects were most apparent for females. These differences could not be explained by gray matter variations. The Met-related profile of activation, particularly prefrontally, predicted greater negativity bias associated with risk for emotional disorder. The findings suggest that the COMT Met allele modulates neural substrates of negative versus positive emotion processing. This effect may contribute to negativity biases, which confer susceptibility for emotional disorders. Copyright 2010 Elsevier Inc. All rights reserved.

Exploring Symmetry to Assist Alzheimer's Disease Diagnosis

NASA Astrophysics Data System (ADS)

Illán, I. A.; Górriz, J. M.; Ramírez, J.; Salas-Gonzalez, D.; López, M.; Padilla, P.; Chaves, R.; Segovia, F.; Puntonet, C. G.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder first affecting memory functions and then gradually affecting all cognitive functions with behavioral impairments and eventually causing death. Functional brain imaging as Single-Photon Emission Computed Tomography (SPECT) is commonly used to guide the clinician's diagnosis. The essential left-right symmetry of human brains is shown to play a key role in coding and recognition. In the present work we explore the implications of this symmetry in AD diagnosis, showing that recognition may be enhanced when considering this latent symmetry.

A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes

PubMed Central

Stomby, Andreas; Otten, Julia; Ryberg, Mats; Nyberg, Lars; Olsson, Tommy; Boraxbekk, Carl-Johan

2017-01-01

Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12) with and without high intensity exercise (PDEX, n = 12) for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group was included as a reference (n = 6). The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced a significant weight loss, improved insulin sensitivity and increased peak oxygen uptake without any significant group differences. Furthermore, both interventions were associated with increased functional brain responses within the right anterior hippocampus, right inferior occipital gyrus and increased volume of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies. Clinical trials registration number: Clinicaltrials. gov NCT01513798. PMID:29255413

A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes.

PubMed

Stomby, Andreas; Otten, Julia; Ryberg, Mats; Nyberg, Lars; Olsson, Tommy; Boraxbekk, Carl-Johan

2017-01-01

Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12) with and without high intensity exercise (PDEX, n = 12) for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group was included as a reference ( n = 6). The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced a significant weight loss, improved insulin sensitivity and increased peak oxygen uptake without any significant group differences. Furthermore, both interventions were associated with increased functional brain responses within the right anterior hippocampus, right inferior occipital gyrus and increased volume of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies. Clinical trials registration number: Clinicaltrials. gov NCT01513798.

Brain-computer interfaces in medicine.

PubMed

Shih, Jerry J; Krusienski, Dean J; Wolpaw, Jonathan R

2012-03-01

Brain-computer interfaces (BCIs) acquire brain signals, analyze them, and translate them into commands that are relayed to output devices that carry out desired actions. BCIs do not use normal neuromuscular output pathways. The main goal of BCI is to replace or restore useful function to people disabled by neuromuscular disorders such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. From initial demonstrations of electroencephalography-based spelling and single-neuron-based device control, researchers have gone on to use electroencephalographic, intracortical, electrocorticographic, and other brain signals for increasingly complex control of cursors, robotic arms, prostheses, wheelchairs, and other devices. Brain-computer interfaces may also prove useful for rehabilitation after stroke and for other disorders. In the future, they might augment the performance of surgeons or other medical professionals. Brain-computer interface technology is the focus of a rapidly growing research and development enterprise that is greatly exciting scientists, engineers, clinicians, and the public in general. Its future achievements will depend on advances in 3 crucial areas. Brain-computer interfaces need signal-acquisition hardware that is convenient, portable, safe, and able to function in all environments. Brain-computer interface systems need to be validated in long-term studies of real-world use by people with severe disabilities, and effective and viable models for their widespread dissemination must be implemented. Finally, the day-to-day and moment-to-moment reliability of BCI performance must be improved so that it approaches the reliability of natural muscle-based function. Copyright © 2012 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Growth and development of the brain and impact on cognitive outcomes.

PubMed

Hüppi, Petra S

2010-01-01

Understanding human brain development from the fetal life to adulthood is of great clinical importance as many neurological and neurobehavioral disorders have their origin in early structural and functional cerebral maturation. The developing brain is particularly prone to being affected by endogenous and exogenous events through the fetal and early postnatal life. The concept of 'developmental plasticity or disruption of the developmental program' summarizes these events. Increases in white matter, which speed up communication between brain cells, growing complexity of neuronal networks suggested by gray and white matter changes, and environmentally sensitive plasticity are all essential aspects in a child's ability to mentalize and maintain the adaptive flexibility necessary for achieving high sociocognitive functioning. Advancement in neuroimaging has opened up new ways for examining the developing human brain in vivo, the study of the effects of early antenatal, perinatal and neonatal events on later structural and functional brain development resulting in developmental disabilities or developmental resilience. In this review, methods of quantitative assessment of human brain development, such as 3D-MRI with image segmentation, diffusion tensor imaging to assess connectivity and functional MRI to visualize brain function will be presented. Copyright (c) 2010 S. Karger AG, Basel.

Gastrointestinal Physiology and Function.

PubMed

Greenwood-Van Meerveld, Beverley; Johnson, Anthony C; Grundy, David

2017-01-01

The gastrointestinal (GI) system is responsible for the digestion and absorption of ingested food and liquids. Due to the complexity of the GI tract and the substantial volume of material that could be covered under the scope of GI physiology, this chapter briefly reviews the overall function of the GI tract, and discusses the major factors affecting GI physiology and function, including the intestinal microbiota, chronic stress, inflammation, and aging with a focus on the neural regulation of the GI tract and an emphasis on basic brain-gut interactions that serve to modulate the GI tract. GI diseases refer to diseases of the esophagus, stomach, small intestine, colon, and rectum. The major symptoms of common GI disorders include recurrent abdominal pain and bloating, heartburn, indigestion/dyspepsia, nausea and vomiting, diarrhea, and constipation. GI disorders rank among the most prevalent disorders, with the most common including esophageal and swallowing disorders, gastric and peptic ulcer disease, gastroparesis or delayed gastric emptying, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Many GI disorders are difficult to diagnose and their symptoms are not effectively managed. Thus, basic research is required to drive the development of novel therapeutics which are urgently needed. One approach is to enhance our understanding of gut physiology and pathophysiology especially as it relates to gut-brain communications since they have clinical relevance to a number of GI complaints and represent a therapeutic target for the treatment of conditions including inflammatory diseases of the GI tract such as IBD and functional gut disorders such as IBS.

Exploration and Modulation of Brain Network Interactions with Noninvasive Brain Stimulation in Combination with Neuroimaging

PubMed Central

Shafi, Mouhsin M.; Westover, M. Brandon; Fox, Michael D.; Pascual-Leone, Alvaro

2012-01-01

Much recent work in systems neuroscience has focused on how dynamic interactions between different cortical regions underlie complex brain functions such as motor coordination, language, and emotional regulation. Various studies using neuroimaging and neurophysiologic techniques have suggested that in many neuropsychiatric disorders, these dynamic brain networks are dysregulated. Here we review the utility of combined noninvasive brain stimulation and neuroimaging approaches towards greater understanding of dynamic brain networks in health and disease. Brain stimulation techniques, such as transcranial magnetic stimulation and transcranial direct current stimulation, use electromagnetic principles to noninvasively alter brain activity, and induce focal but also network effects beyond the stimulation site. When combined with brain imaging techniques such as functional MRI, PET and EEG, these brain stimulation techniques enable a causal assessment of the interaction between different network components, and their respective functional roles. The same techniques can also be applied to explore hypotheses regarding the changes in functional connectivity that occur during task performance and in various disease states such as stroke, depression and schizophrenia. Finally, in diseases characterized by pathologic alterations in either the excitability within a single region or in the activity of distributed networks, such techniques provide a potential mechanism to alter cortical network function and architectures in a beneficial manner. PMID:22429242

Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour.

PubMed

Lesch, Klaus-Peter; Araragi, Naozumi; Waider, Jonas; van den Hove, Daniel; Gutknecht, Lise

2012-09-05

Aggression, which comprises multi-faceted traits ranging from negative emotionality to antisocial behaviour, is influenced by an interaction of biological, psychological and social variables. Failure in social adjustment, aggressiveness and violence represent the most detrimental long-term outcome of neurodevelopmental disorders. With the exception of brain-specific tryptophan hydroxylase-2 (Tph2), which generates serotonin (5-HT) in raphe neurons, the contribution of gene variation to aggression-related behaviour in genetically modified mouse models has been previously appraised (Lesch 2005 Novartis Found Symp. 268, 111-140; Lesch & Merschdorf 2000 Behav. Sci. Law 18, 581-604). Genetic inactivation of Tph2 function in mice led to the identification of phenotypic changes, ranging from growth retardation and late-onset obesity, to enhanced conditioned fear response, increased aggression and depression-like behaviour. This spectrum of consequences, which are amplified by stress-related epigenetic interactions, are attributable to deficient brain 5-HT synthesis during development and adulthood. Human data relating altered TPH2 function to personality traits of negative emotionality and neurodevelopmental disorders characterized by deficits in cognitive control and emotion regulation are based on genetic association and are therefore not as robust as the experimental mouse results. Mouse models in conjunction with approaches focusing on TPH2 variants in humans provide unexpected views of 5-HT's role in brain development and in disorders related to negative emotionality, aggression and antisocial behaviour.

ADHD- and Medication-Related Brain Activation Effects in Concordantly Affected Parent-Child Dyads with ADHD

ERIC Educational Resources Information Center

Epstein, Jeffery N.; Casey, B. J.; Tonev, Simon T.; Davidson, Matthew C.; Reiss, Allan L.; Garrett, Amy; Hinshaw, Stephen P.; Greenhill, Laurence L.; Glover, Gary; Shafritz, Keith M.; Vitolo, Alan; Kotler, Lisa A.; Jarrett, Matthew A.; Spicer, Julie

2007-01-01

Background: Several studies have documented fronto-striatal dysfunction in children and adolescents with attention deficit/hyperactivity disorder (ADHD) using response inhibition tasks. Our objective was to examine functional brain abnormalities among youths and adults with ADHD and to examine the relations between these neurobiological…

Identifying disease-related subnetwork connectome biomarkers by sparse hypergraph learning.

PubMed

Zu, Chen; Gao, Yue; Munsell, Brent; Kim, Minjeong; Peng, Ziwen; Cohen, Jessica R; Zhang, Daoqiang; Wu, Guorong

2018-06-14

The functional brain network has gained increased attention in the neuroscience community because of its ability to reveal the underlying architecture of human brain. In general, majority work of functional network connectivity is built based on the correlations between discrete-time-series signals that link only two different brain regions. However, these simple region-to-region connectivity models do not capture complex connectivity patterns between three or more brain regions that form a connectivity subnetwork, or subnetwork for short. To overcome this current limitation, a hypergraph learning-based method is proposed to identify subnetwork differences between two different cohorts. To achieve our goal, a hypergraph is constructed, where each vertex represents a subject and also a hyperedge encodes a subnetwork with similar functional connectivity patterns between different subjects. Unlike previous learning-based methods, our approach is designed to jointly optimize the weights for all hyperedges such that the learned representation is in consensus with the distribution of phenotype data, i.e. clinical labels. In order to suppress the spurious subnetwork biomarkers, we further enforce a sparsity constraint on the hyperedge weights, where a larger hyperedge weight indicates the subnetwork with the capability of identifying the disorder condition. We apply our hypergraph learning-based method to identify subnetwork biomarkers in Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). A comprehensive quantitative and qualitative analysis is performed, and the results show that our approach can correctly classify ASD and ADHD subjects from normal controls with 87.65 and 65.08% accuracies, respectively.

The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders

PubMed Central

Kundakovic, Marija; Jaric, Ivana

2017-01-01

Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf). These epigenetic changes have been linked to changes in brain gene expression, stress reactivity, and behavior, and often times, these effects are shown to be dependent on the gestational window of exposure, sex, and exposure level. Although evidence from human studies is more limited, gestational exposure to environmental risks in humans is associated with epigenetic changes in peripheral tissues, and future studies are required to understand whether we can use peripheral biomarkers to predict neurobehavioral outcomes. An extensive research effort combining well-designed human and animal studies, with comprehensive epigenomic analyses of peripheral and brain tissues over time, will be necessary to improve our understanding of the epigenetic basis of neurodevelopmental disorders. PMID:28335457

A Window into the Brain: Advances in Psychiatric fMRI

PubMed Central

Zhan, Xiaoyan

2015-01-01

Functional magnetic resonance imaging (fMRI) plays a key role in modern psychiatric research. It provides a means to assay differences in brain systems that underlie psychiatric illness, treatment response, and properties of brain structure and function that convey risk factor for mental diseases. Here we review recent advances in fMRI methods in general use and progress made in understanding the neural basis of mental illness. Drawing on concepts and findings from psychiatric fMRI, we propose that mental illness may not be associated with abnormalities in specific local regions but rather corresponds to variation in the overall organization of functional communication throughout the brain network. Future research may need to integrate neuroimaging information drawn from different analysis methods and delineate spatial and temporal patterns of brain responses that are specific to certain types of psychiatric disorders. PMID:26413531

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

Common and distinct changes of default mode and salience network in schizophrenia and major depression.

PubMed

Shao, Junming; Meng, Chun; Tahmasian, Masoud; Brandl, Felix; Yang, Qinli; Luo, Guangchun; Luo, Cheng; Yao, Dezhong; Gao, Lianli; Riedl, Valentin; Wohlschläger, Afra; Sorg, Christian

2018-02-19

Brain imaging reveals schizophrenia as a disorder of macroscopic brain networks. In particular, default mode and salience network (DMN, SN) show highly consistent alterations in both interacting brain activity and underlying brain structure. However, the same networks are also altered in major depression. This overlap in network alterations induces the question whether DMN and SN changes are different across both disorders, potentially indicating distinct underlying pathophysiological mechanisms. To address this question, we acquired T1-weighted, diffusion-weighted, and resting-state functional MRI in patients with schizophrenia, patients with major depression, and healthy controls. We measured regional gray matter volume, inter-regional structural and intrinsic functional connectivity of DMN and SN, and compared these measures across groups by generalized Wilcoxon rank tests, while controlling for symptoms and medication. When comparing patients with controls, we found in each patient group SN volume loss, impaired DMN structural connectivity, and aberrant DMN and SN functional connectivity. When comparing patient groups, SN gray matter volume loss and DMN structural connectivity reduction did not differ between groups, but in schizophrenic patients, functional hyperconnectivity between DMN and SN was less in comparison to depressed patients. Results provide evidence for distinct functional hyperconnectivity between DMN and SN in schizophrenia and major depression, while structural changes in DMN and SN were similar. Distinct hyperconnectivity suggests different pathophysiological mechanism underlying aberrant DMN-SN interactions in schizophrenia and depression.

Connectivity Neurofeedback Training Can Differentially Change Functional Connectivity and Cognitive Performance.

PubMed

Yamashita, Ayumu; Hayasaka, Shunsuke; Kawato, Mitsuo; Imamizu, Hiroshi

2017-10-01

Advances in functional magnetic resonance imaging have made it possible to provide real-time feedback on brain activity. Neurofeedback has been applied to therapeutic interventions for psychiatric disorders. Since many studies have shown that most psychiatric disorders exhibit abnormal brain networks, a novel experimental paradigm named connectivity neurofeedback, which can directly modulate a brain network, has emerged as a promising approach to treat psychiatric disorders. Here, we investigated the hypothesis that connectivity neurofeedback can induce the aimed direction of change in functional connectivity, and the differential change in cognitive performance according to the direction of change in connectivity. We selected the connectivity between the left primary motor cortex and the left lateral parietal cortex as the target. Subjects were divided into 2 groups, in which only the direction of change (an increase or a decrease in correlation) in the experimentally manipulated connectivity differed between the groups. As a result, subjects successfully induced the expected connectivity changes in either of the 2 directions. Furthermore, cognitive performance significantly and differentially changed from preneurofeedback to postneurofeedback training between the 2 groups. These findings indicate that connectivity neurofeedback can induce the aimed direction of change in connectivity and also a differential change in cognitive performance. © The Author 2017. Published by Oxford University Press.

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.

Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)?

PubMed

Elzinga, B M; Bremner, J D

2002-06-01

A model for the posttraumatic stress disorder (PTSD) as a disorder of memory is presented drawing both on psychological and neurobiological data. Evidence on intrusive memories and deficits in declarative memory function in PTSD-patients is reviewed in relation to three brain areas that are involved in memory functioning and the stress response: the hippocampus, amygdala, and the prefrontal cortex. Neurobiological studies have shown that the noradrenergic stress-system is involved in enhanced encoding of emotional memories, sensitization, and fear conditioning, by way of its effects on the amygdala. Chronic stress also affects the hippocampus, a brain area involved in declarative memories, suggesting that hippocampal dysfunction may partly account for the deficits in declarative memory in PTSD-patients. Deficits in the medial prefrontal cortex, a structure that normally inhibits the amygdala, may further enhance the effects of the amygdala, thereby increasing the frequency and intensity of the traumatic memories. Thus, by way of its influence on these brain structures, exposure to severe stress may simultaneously result in strong emotional reactions and in difficulties to recall the emotional event. This model is also relevant for understanding the distinction between declarative and non-declarative memory-functions in processing trauma-related information in PTSD. Implications of our model are reviewed.

Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)?

PubMed Central

Elzinga, B.M.; Bremner, J.D.

2017-01-01

A model for the posttraumatic stress disorder (PTSD) as a disorder of memory is presented drawing both on psychological and neurobiological data. Evidence on intrusive memories and deficits in declarative memory function in PTSD-patients is reviewed in relation to three brain areas that are involved in memory functioning and the stress response: the hippocampus, amygdala, and the prefrontal cortex. Neurobiological studies have shown that the noradrenergic stress-system is involved in enhanced encoding of emotional memories, sensitization, and fear conditioning, by way of its effects on the amygdala. Chronic stress also affects the hippocampus, a brain area involved in declarative memories, suggesting that hippocampal dysfunction may partly account for the deficits in declarative memory in PTSD-patients. Deficits in the medial prefrontal cortex, a structure that normally inhibits the amygdala, may further enhance the effects of the amygdala, thereby increasing the frequency and intensity of the traumatic memories. Thus, by way of its influence on these brain structures, exposure to severe stress may simultaneously result in strong emotional reactions and in difficulties to recall the emotional event. This model is also relevant for understanding the distinction between declarative and non-declarative memory-functions in processing trauma-related information in PTSD. Implications of our model are reviewed. PMID:12113915

Sigma receptors: biology and therapeutic potential.

PubMed

Guitart, Xavier; Codony, Xavier; Monroy, Xavier

2004-07-01

More than 20 years after the identification of the sigma receptors as a unique binding site in the brain and in the peripheral organs, several questions regarding this receptor are still open. Only one of the subtypes of the receptor has been cloned to date, but the endogenous ligand still remains unknown, and the possible association of the receptor with a conventional second messenger system is controversial. From the very beginning, the sigma receptors were associated with various central nervous system disorders such as schizophrenia or movement disorders. Today, after hundreds of papers dealing with the importance of sigma receptors in brain function, it is widely accepted that sigma receptors represent a new and different avenue in the possible pharmacological treatment of several brain-related disorders. In this review, what is known about the biology of the sigma receptor regarding its putative structure and its distribution in the central nervous system is summarized first. The role of sigma receptors regulating cellular functions and other neurotransmitter systems is also addressed, as well as a short overview of the possible endogenous ligands. Finally, although no specific sigma ligand has reached the market, different pharmacological approaches to the alleviation and treatment of several central nervous system disorders and deficits, including schizophrenia, pain, memory deficits, etc., are discussed, with an overview of different compounds and their potential therapeutic use.

The role of genes and environment on brain alterations in Major Depressive Disorder: A review of twin studies: Special Section on "Translational and Neuroscience Studies in Affective Disorders". Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

PubMed

Pigoni, A; Delvecchio, G; Altamura, A C; Soares, J C; Fagnani, C; Brambilla, P

2018-07-01

Although it has been consistently reported the important role of genetic and environmental risk factors on structural and functional alterations in Major Depressive Disorder (MDD), the mechanism and the magnitude of the interactions between specific genetic and/or environmental risk factors on brain structures in this disabling disorder are still elusive. Therefore, in the last two decades an increased interest has been devoted to neuroimaging investigations on monozygotic and dizygotic twin samples mainly because their intrinsic characteristics may help to separate the effects of genetic and environmental risk factors on clinical phenotypes, including MDD. In this context, the present review summarizes results from structural and functional Magnetic Resonance Imaging studies that investigated twin samples in correlation with MDD. Overall the results confirmed that a) MDD is characterized by significant alterations in selective brain areas presiding over emotion recognition and evaluation, including amygdala, insula and prefrontal cortices, and b) both genetic and environmental risk factors play a key role in the pathophysiology of this disorder. Few MRI studies exploring MDD in twin samples. The specific contribution of both aspects is still not fully elucidated especially because genes and environment have an impact on the same brain areas, which are particularly vulnerable in MDD. Expansion of the current twin sample sizes would help to clearly establish the potential relationship between risk factors and the development of MDD. Copyright © 2017 Elsevier B.V. All rights reserved.

Pericytes of the neurovascular unit: Key functions and signaling pathways

PubMed Central

Sweeney, Melanie D.; Ayyadurai, Shiva; Zlokovic, Berislav V.

2017-01-01

Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles, and post-capillary venules. The central nervous system (CNS) pericytes are uniquely positioned within the neurovascular unit between endothelial cells, astrocytes, and neurons. They integrate, coordinate, and process signals from their neighboring cells to generate diverse functional responses that are critical for CNS functions in health and disease including regulation of the blood-brain barrier permeability, angiogenesis, clearance of toxic metabolites, capillary hemodynamic responses, neuroinflammation, and stem cell activity. Here, we examine the key signaling pathways between pericytes and their neighboring endothelial cells, astrocytes, and neurons that control neurovascular functions. We also review the role of pericytes in different CNS disorders including rare monogenic diseases and complex neurological disorders such as Alzheimer's disease and brain tumors. Finally, we discuss directions for future studies. PMID:27227366

Functional magnetic resonance imaging of chronic dysarthric speech after childhood brain injury: reliance on a left-hemisphere compensatory network.

PubMed

Morgan, Angela T; Masterton, Richard; Pigdon, Lauren; Connelly, Alan; Liégeois, Frédérique J

2013-02-01

Severe and persistent speech disorder, dysarthria, may be present for life after brain injury in childhood, yet the neural correlates of this chronic disorder remain elusive. Although abundant literature is available on language reorganization after lesions in childhood, little is known about the capacity of motor speech networks to reorganize after injury. Here, we examine the structural and functional neural correlates associated with chronic dysarthria after childhood-onset traumatic brain injury. Forty-nine participants aged 12 years 3 months to 24 years 11 months were recruited to the study: (i) a group with chronic dysarthria (n = 17); matched for age and sex with two control groups of (ii) healthy control subjects (n = 17); and (iii) individuals without dysarthria after traumatic brain injury (n = 15). A high-resolution 3D T(1)-weighted whole-brain data set was acquired for voxel-based morphometry analyses of group differences in grey matter. Functional magnetic resonance imaging was used to localize activation associated with speaking single words (baseline: listening to words). Group differences on voxel-based morphometry revealed widespread grey matter reductions in the dysarthric group compared with healthy control subjects, including in numerous speech motor regions bilaterally, such as the cerebellum, the basal ganglia and primary motor cortex representation of the articulators. Relative to the non-dysarthric traumatic brain injury group, individuals with dysarthria showed reduced grey matter bilaterally in the ventral sensorimotor cortex, but this reduction was concomitant with increased functional activation only in the left-hemisphere cluster during speech. Finally, increased recruitment of Broca's area (Brodmann area 45, pars triangularis) but not its right homologue, correlated with better speech outcome, suggesting that this 'higher-level' area may be more critically involved with production when associated motor speech regions are damaged. We suggest that the bilateral morphological abnormalities within cortical speech networks in childhood prevented reorganization of speech function from the left- to right-hemisphere. Rather, functional reorganization involved over-recruitment of left-hemisphere motor regions, a reorganization method that was only partly relatively effective, given the presence of persisting yet mild speech deficits. The bilateral structural abnormalities found to limit functional reorganization here, may also be critical to poor speech prognosis for populations with congenital, degenerative or acquired neurological disorders throughout the lifespan.

Abnormal Functional Lateralization and Activity of Language Brain Areas in Typical Specific Language Impairment (Developmental Dysphasia)

ERIC Educational Resources Information Center

de Guibert, Clement; Maumet, Camille; Jannin, Pierre; Ferre, Jean-Christophe; Treguier, Catherine; Barillot, Christian; Le Rumeur, Elisabeth; Allaire, Catherine; Biraben, Arnaud

2011-01-01

Atypical functional lateralization and specialization for language have been proposed to account for developmental language disorders, yet results from functional neuroimaging studies are sparse and inconsistent. This functional magnetic resonance imaging study compared children with a specific subtype of specific language impairment affecting…

Ethical and Clinical Considerations at the Intersection of Functional Neuroimaging and Disorders of Consciousness.

PubMed

Byram, Adrian C; Lee, Grace; Owen, Adrian M; Ribary, Urs; Stoessl, A Jon; Townson, Andrea; Illes, Judy

2016-10-01

Recent neuroimaging research on disorders of consciousness provides direct evidence of covert consciousness otherwise not detected clinically in a subset of severely brain-injured patients. These findings have motivated strategic development of binary communication paradigms, from which researchers interpret voluntary modulations in brain activity to glean information about patients' residual cognitive functions and emotions. The discovery of such responsiveness raises ethical and legal issues concerning the exercise of autonomy and capacity for decisionmaking on matters such as healthcare, involvement in research, and end of life. These advances have generated demands for access to the technology against a complex background of continued scientific advancement, questions about just allocation of healthcare resources, and unresolved legal issues. Interviews with professionals whose work is relevant to patients with disorders of consciousness reveal priorities concerning further basic research, legal and policy issues, and clinical considerations.

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.

Brain function and conditioning in posttraumatic stress disorder.

PubMed

Redgrave, K

2003-06-01

Posttraumatic stress disorder (PTSD) is commonly treated by psychotherapy, which may draw upon behavioural psychology or cognitive-behavioural psychology, thereby making use of desensitisation techniques--amongst others; hypnotherapy may also be used. Hypnotherapy and psychotherapy are also available for helping patients who suffer from symptoms associated with general stress or who show phobic symptoms, such as a fear of heights or of walking across bridges. Studies of patients with such disorders have not always linked emotional (affective) and behavioural symptoms with psychophysical factors, which correlate with the symptoms. The present article not only does this, but also shows that it is possible for brain function and psychoemotional outcome to mislead a person and 'trick' him or her into believing that certain fears or panics appear 'out of the blue' or might be due to experiences other than the true cause. These may be important when, for instance, childhood memories form an issue in any court case.

Resting-State Functional Connectivity in Autism Spectrum Disorders: A Review

PubMed Central

Hull, Jocelyn V.; Jacokes, Zachary J.; Torgerson, Carinna M.; Irimia, Andrei; Van Horn, John Darrell

2017-01-01

Ongoing debate exists within the resting-state functional MRI (fMRI) literature over how intrinsic connectivity is altered in the autistic brain, with reports of general over-connectivity, under-connectivity, and/or a combination of both. Classifying autism using brain connectivity is complicated by the heterogeneous nature of the condition, allowing for the possibility of widely variable connectivity patterns among individuals with the disorder. Further differences in reported results may be attributable to the age and sex of participants included, designs of the resting-state scan, and to the analysis technique used to evaluate the data. This review systematically examines the resting-state fMRI autism literature to date and compares studies in an attempt to draw overall conclusions that are presently challenging. We also propose future direction for rs-fMRI use to categorize individuals with autism spectrum disorder, serve as a possible diagnostic tool, and best utilize data-sharing initiatives. PMID:28101064

Brain-computer interfaces in neurological rehabilitation.

PubMed

Daly, Janis J; Wolpaw, Jonathan R

2008-11-01

Recent advances in analysis of brain signals, training patients to control these signals, and improved computing capabilities have enabled people with severe motor disabilities to use their brain signals for communication and control of objects in their environment, thereby bypassing their impaired neuromuscular system. Non-invasive, electroencephalogram (EEG)-based brain-computer interface (BCI) technologies can be used to control a computer cursor or a limb orthosis, for word processing and accessing the internet, and for other functions such as environmental control or entertainment. By re-establishing some independence, BCI technologies can substantially improve the lives of people with devastating neurological disorders such as advanced amyotrophic lateral sclerosis. BCI technology might also restore more effective motor control to people after stroke or other traumatic brain disorders by helping to guide activity-dependent brain plasticity by use of EEG brain signals to indicate to the patient the current state of brain activity and to enable the user to subsequently lower abnormal activity. Alternatively, by use of brain signals to supplement impaired muscle control, BCIs might increase the efficacy of a rehabilitation protocol and thus improve muscle control for the patient.

The Neurobiology of Moral Behavior: Review and Neuropsychiatric Implications

PubMed Central

Mendez, Mario F.

2011-01-01

Morality may be innate to the human brain. This review examines the neurobiological evidence from research involving functional magnetic resonance imaging of normal subjects, developmental sociopathy, acquired sociopathy from brain lesions, and frontotemporal dementia. These studies indicate a “neuromoral” network for responding to moral dilemmas centered in the ventromedial prefrontal cortex and its connections, particularly on the right. The neurobiological evidence indicates the existence of automatic “prosocial” mechanisms for identification with others that are part of the moral brain. Patients with disorders involving this moral network have attenuated emotional reactions to the possibility of harming others and may perform sociopathic acts. The existence of this neuromoral system has major clinical implications for the management of patients with dysmoral behavior from brain disorders and for forensic neuropsychiatry. PMID:20173686

Mapping the functional connectome traits of levels of consciousness.

PubMed

Amico, Enrico; Marinazzo, Daniele; Di Perri, Carol; Heine, Lizette; Annen, Jitka; Martial, Charlotte; Dzemidzic, Mario; Kirsch, Murielle; Bonhomme, Vincent; Laureys, Steven; Goñi, Joaquín

2017-03-01

Examining task-free functional connectivity (FC) in the human brain offers insights on how spontaneous integration and segregation of information relate to human cognition, and how this organization may be altered in different conditions, and neurological disorders. This is particularly relevant for patients in disorders of consciousness (DOC) following severe acquired brain damage and coma, one of the most devastating conditions in modern medical care. We present a novel data-driven methodology, connICA, which implements Independent Component Analysis (ICA) for the extraction of robust independent FC patterns (FC-traits) from a set of individual functional connectomes, without imposing any a priori data stratification into groups. We here apply connICA to investigate associations between network traits derived from task-free FC and cognitive/clinical features that define levels of consciousness. Three main independent FC-traits were identified and linked to consciousness-related clinical features. The first one represents the functional configuration of a "resting" human brain, and it is associated to a sedative (sevoflurane), the overall effect of the pathology and the level of arousal. The second FC-trait reflects the disconnection of the visual and sensory-motor connectivity patterns. It also relates to the time since the insult and to the ability of communicating with the external environment. The third FC-trait isolates the connectivity pattern encompassing the fronto-parietal and the default-mode network areas as well as the interaction between left and right hemispheres, which are also associated to the awareness of the self and its surroundings. Each FC-trait represents a distinct functional process with a role in the degradation of conscious states of functional brain networks, shedding further light on the functional sub-circuits that get disrupted in severe brain-damage. Copyright © 2017. Published by Elsevier Inc.

5-HT7 receptors as modulators of neuronal excitability, synaptic transmission and plasticity: physiological role and possible implications in autism spectrum disorders

PubMed Central

Ciranna, Lucia; Catania, Maria Vincenza

2014-01-01

Serotonin type 7 receptors (5-HT7) are expressed in several brain areas, regulate brain development, synaptic transmission and plasticity, and therefore are involved in various brain functions such as learning and memory. A number of studies suggest that 5-HT7 receptors could be potential pharmacotherapeutic target for cognitive disorders. Several abnormalities of serotonergic system have been described in patients with autism spectrum disorder (ASD), including abnormal activity of 5-HT transporter, altered blood and brain 5-HT levels, reduced 5-HT synthesis and altered expression of 5-HT receptors in the brain. A specific role for 5-HT7 receptors in ASD has not yet been demonstrated but some evidence implicates their possible involvement. We have recently shown that 5-HT7 receptor activation rescues hippocampal synaptic plasticity in a mouse model of Fragile X Syndrome, a monogenic cause of autism. Several other studies have shown that 5-HT7 receptors modulate behavioral flexibility, exploratory behavior, mood disorders and epilepsy, which include core and co-morbid symptoms of ASD. These findings further suggest an involvement of 5-HT7 receptors in ASD. Here, we review the physiological roles of 5-HT7 receptors and their implications in Fragile X Syndrome and other ASD. PMID:25221471

Local functional connectivity suggests functional immaturity in children with attention-deficit/hyperactivity disorder.

PubMed

Marcos-Vidal, Luis; Martínez-García, Magdalena; Pretus, Clara; Garcia-Garcia, David; Martínez, Kenia; Janssen, Joost; Vilarroya, Oscar; Castellanos, Francisco X; Desco, Manuel; Sepulcre, Jorge; Carmona, Susanna

2018-06-01

Previous studies have associated Attention-Deficit/Hyperactivity Disorder (ADHD) with a maturational lag of brain functional networks. Functional connectivity of the human brain changes from primarily local to more distant connectivity patterns during typical development. Under the maturational lag hypothesis, we expect children with ADHD to exhibit increased local connectivity and decreased distant connectivity compared with neurotypically developing (ND) children. We applied a graph-theory method to compute local and distant connectivity levels and cross-sectionally compared them in a sample of 120 children with ADHD and 120 age-matched ND children (age range = 7-17 years). In addition, we measured if potential group differences in local and distant connectivity were stable across the age range considered. Finally, we assessed the clinical relevance of observed group differences by correlating the connectivity levels and ADHD symptoms severity separately for each group. Children with ADHD exhibited more local connectivity than age-matched ND children in multiple brain regions, mainly overlapping with default mode, fronto-parietal and ventral attentional functional networks (p < .05- threshold free-cluster enhancement-family-wise error). We detected an atypical developmental pattern of local connectivity in somatomotor regions, that is, decreases with age in ND children, and increases with age in children with ADHD. Furthermore, local connectivity within somatomotor areas correlated positively with clinical severity of ADHD symptoms, both in ADHD and ND children. Results suggest an immature functional state of multiple brain networks in children with ADHD. Whereas the ADHD diagnosis is associated with the integrity of the system comprising the fronto-parietal, default mode and ventral attentional networks, the severity of clinical symptoms is related to atypical functional connectivity within somatomotor areas. Additionally, our findings are in line with the view of ADHD as a disorder of deviated maturational trajectories, mainly affecting somatomotor areas, rather than delays that normalize with age. © 2018 Wiley Periodicals, Inc.

Towards ultrahigh resting-state functional connectivity in the mouse brain using photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Hariri, Ali; Bely, Nicholas; Chen, Chen; Nasiriavanaki, Mohammadreza

2016-03-01

The increasing use of mouse models for human brain disease studies, coupled with the fact that existing high-resolution functional imaging modalities cannot be easily applied to mice, presents an emerging need for a new functional imaging modality. Utilizing both mechanical and optical scanning in the photoacoustic microscopy, we can image spontaneous cerebral hemodynamic fluctuations and their associated functional connections in the mouse brain. The images is going to be acquired noninvasively with a fast frame rate, a large field of view, and a high spatial resolution. We developed an optical resolution photoacoustic microscopy (OR-PAM) with diode laser. Laser light was raster scanned due to XY-stage movement. Images from ultra-high OR-PAM can then be used to study brain disorders such as stroke, Alzheimer's, schizophrenia, multiple sclerosis, autism, and epilepsy.

Understanding Neuropsychiatric Diseases, Analyzing the Peptide Sharing between Infectious Agents and the Language-Associated NMDA 2A Protein.

PubMed

Lucchese, Guglielmo

2016-01-01

Language disorders and infections may occur together and often concur, to a different extent and via different modalities, in characterizing brain pathologies, such as schizophrenia, autism, epilepsies, bipolar disorders, frontotemporal neurodegeneration, and encephalitis, inter alia. The biological mechanism(s) that might channel language dysfunctions and infections into etiological pathways connected to neuropathologic sequelae are unclear. Searching for molecular link(s) between language disorders and infections, the present study explores the language-associated NMDA 2A subunit for peptide sharing with pathogens that have been described in concomitance with neuropsychiatric diseases. It was found that a vast peptide commonality links the human glutamate ionotropic receptor NMDA 2A subunit to infectious agents. Such a link expands to and interfaces with neuropsychiatric disorders in light of the specific allocation of NMDA 2A gene expression in brain areas related to language functions. The data hint at a possible pathologic scenario based on anti-pathogen immune responses cross-reacting with NMDA 2A in the brain.

Development of large-scale functional brain networks in children.

PubMed

Supekar, Kaustubh; Musen, Mark; Menon, Vinod

2009-07-01

The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism.

Development of Large-Scale Functional Brain Networks in Children

PubMed Central

Supekar, Kaustubh; Musen, Mark; Menon, Vinod

2009-01-01

The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7–9 y) and 22 young-adults (ages 19–22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar “small-world” organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism. PMID:19621066

Degree connectivity in body dysmorphic disorder and relationships with obsessive and compulsive symptoms.

PubMed

Beucke, Jan C; Sepulcre, Jorge; Buhlmann, Ulrike; Kathmann, Norbert; Moody, Teena; Feusner, Jamie D

2016-10-01

Individuals with body dysmorphic disorder (BDD) and obsessive-compulsive disorder (OCD) are categorized within the same major diagnostic group and both show regional brain hyperactivity in the orbitofrontal cortex (OFC) and the basal ganglia during symptom provocation. While recent studies revealed that degree connectivity of these areas is abnormally high in OCD and positively correlates with symptom severity, no study has investigated degree connectivity in BDD. We used functional magnetic resonance imaging (fMRI) to compare the local and distant degree of functional connectivity in all brain areas between 28 unmedicated BDD participants and 28 demographically matched healthy controls during a face-processing task. Correlational analyses tested for associations between degree connectivity and symptom severity assessed by the BDD version of the Yale-Brown obsessive-compulsive scale (BDD-Y-BOCS). Reduced local amygdalar connectivity was found in participants with BDD. No differences in distant connectivity were found. BDD-Y-BOCS scores significantly correlated with the local connectivity of the posterior-lateral OFC, and distant connectivity of the posterior-lateral and post-central OFC, respectively. These findings represent preliminary evidence that individuals with BDD exhibit brain-behavioral associations related to obsessive thoughts and compulsive behaviors that are highly similar to correlations previously found in OCD, further underscoring their related pathophysiology. This relationship could be further elucidated through investigation of resting-state functional connectivity in BDD, ideally in direct comparison with OCD and other obsessive-compulsive and related disorders. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Decreased functional connectivity in an executive control network is related to impaired executive function in Internet gaming disorder.

PubMed

Dong, Guangheng; Lin, Xiao; Potenza, Marc N

2015-03-03

Resting brain spontaneous neural activities across cortical regions have been correlated with specific functional properties in psychiatric groups. Individuals with Internet gaming disorder (IGD) demonstrate impaired executive control. Thus, it is important to examine executive control networks (ECNs) during resting states and their relationships to executive control during task performance. Thirty-five IGD and 36 healthy control participants underwent a resting-state fMRI scan and performed a Stroop task inside and outside of the MRI scanner. Correlations between Stroop effect and functional connectivity among ECN regions of interest (ROIs) were calculated within and between groups. IGD subjects show lower functional connectivity in ECNs than do HC participants during resting state; functional-connectivity measures in ECNs were negatively correlated with Stroop effect and positively correlated with brain activations in executive-control regions across groups. Within groups, negative trends were found between Stroop effect and functional connectivity in ECNs in IGD and HC groups, separately; positive trends were found between functional connectivity in ECNs and brain activations in Stroop task in IGD and HC groups, separately. Higher functional connectivity in ECNs may underlie better executive control and may provide resilience with respect to IGD. Lower functional connectivity in ECNs may represent an important feature in understanding and treating IGD. Copyright © 2013 Elsevier Inc. All rights reserved.

A preliminary study of the effects of working memory training on brain function in Attention-Deficit/Hyperactivity Disorder

PubMed Central

Stevens, Michael C.; Gaynor, Alexandra; Bessette, Katie L.; Pearlson, Godfrey D.

2015-01-01

Working memory (WM) training improves WM ability in Attention-Deficit/Hyperactivity Disorder (ADHD), but its efficacy for non-cognitive ADHD impairments ADHD has been sharply debated. The purpose of this preliminary study was to characterize WM training-related changes in ADHD brain function and see if they were linked to clinical improvement. We examined 18 adolescents diagnosed with DSM-IV Combined-subtype ADHD before and after 25 sessions of WM training using a frequently employed approach (CogmedTM) using a nonverbal Sternberg WM fMRI task, neuropsychological tests, and participant- and parent-reports of ADHD symptom severity and associated functional impairment. Whole brain SPM8 analyses identified ADHD activation deficits compared to 18 non-ADHD control participants, then tested whether impaired ADHD frontoparietal brain activation would increase following WM training. Post hoc tests examined the relationships between neural changes and neurocognitive or clinical improvements. As predicted, WM training increased WM performance, ADHD clinical functioning, and WM-related ADHD brain activity in several frontal, parietal and temporal lobe regions. Increased left inferior frontal sulcus region activity was seen in all Encoding, Maintenance, and Retrieval Sternberg task phases. ADHD symptom severity improvements were most often positively correlated with activation gains in brain regions known to be engaged for WM-related executive processing; improvement of different symptom types had different neural correlates. The responsiveness of both amodal WM frontoparietal circuits and executive process-specific WM brain regions was altered by WM training. The latter might represent a promising, relatively unexplored treatment target for researchers seeking to optimize clinical response in ongoing ADHD WM training development efforts. PMID:26138580

Abnormal functional activation and maturation of ventromedial prefrontal cortex and cerebellum during temporal discounting in autism spectrum disorder.

PubMed

Murphy, Clodagh M; Christakou, Anastasia; Giampietro, Vincent; Brammer, Michael; Daly, Eileen M; Ecker, Christine; Johnston, Patrick; Spain, Debbie; Robertson, Dene M; Murphy, Declan G; Rubia, Katya

2017-11-01

People with autism spectrum disorder (ASD) have poor decision-making and temporal foresight. This may adversely impact on their everyday life, mental health, and productivity. However, the neural substrates underlying poor choice behavior in people with ASD, or its' neurofunctional development from childhood to adulthood, are unknown. Despite evidence of atypical structural brain development in ASD, investigation of functional brain maturation in people with ASD is lacking. This cross-sectional developmental fMRI study investigated the neural substrates underlying performance on a temporal discounting (TD) task in 38 healthy (11-35 years old) male adolescents and adults with ASD and 40 age, sex, and IQ-matched typically developing healthy controls. Most importantly, we assessed group differences in the neurofunctional maturation of TD across childhood and adulthood. Males with ASD had significantly poorer task performance and significantly lower brain activation in typical regions that mediate TD for delayed choices, in predominantly right hemispheric regions of ventrolateral/dorsolateral prefrontal cortices, ventromedial prefrontal cortex, striatolimbic regions, and cerebellum. Importantly, differential activation in ventromedial frontal cortex and cerebellum was associated with abnormal functional brain maturation; controls, in contrast to people with ASD, showed progressively increasing activation with increasing age in these regions; which furthermore was associated with performance measures and clinical ASD measures (stereotyped/restricted interests). Findings provide first cross-sectional evidence that reduced activation of TD mediating brain regions in people with ASD during TD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of ASD. Hum Brain Mapp 38:5343-5355, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers

PubMed Central

Rempe, Ralf G; Hartz, Anika MS

2016-01-01

Matrix metalloproteinases are versatile endopeptidases with many different functions in the body in health and disease. In the brain, matrix metalloproteinases are critical for tissue formation, neuronal network remodeling, and blood–brain barrier integrity. Many reviews have been published on matrix metalloproteinases before, most of which focus on the two best studied matrix metalloproteinases, the gelatinases MMP-2 and MMP-9, and their role in one or two diseases. In this review, we provide a broad overview of the role various matrix metalloproteinases play in brain disorders. We summarize and review current knowledge and understanding of matrix metalloproteinases in the brain and at the blood–brain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer’s disease, Parkinson’s disease, and brain cancer. We discuss the detrimental effects matrix metalloproteinases can have in these conditions, contributing to blood–brain barrier leakage, neuroinflammation, neurotoxicity, demyelination, tumor angiogenesis, and cancer metastasis. We also discuss the beneficial role matrix metalloproteinases can play in neuroprotection and anti-inflammation. Finally, we address matrix metalloproteinases as potential therapeutic targets. Together, in this comprehensive review, we summarize current understanding and knowledge of matrix metalloproteinases in the brain and at the blood–brain barrier in brain disorders. PMID:27323783

A Lifespan Approach to Neuroinflammatory and Cognitive Disorders: A Critical Role for Glia

PubMed Central

Bilbo, Staci D.; Smith, Susan H.; Schwarz, Jaclyn M.

2011-01-01

Cognitive decline is a common problem of aging. Whereas multiple neural and glial mechanisms may account for these declines, microglial sensitization and/or dystrophy has emerged as a leading culprit in brain aging and dysfunction. However, glial activation is consistently observed in normal brain aging as well, independent of frank neuroinflammation or functional impairment. Such variability suggests the existence of additional vulnerability factors that can impact neuronal-glial interactions and thus overall brain and cognitive health. The goal of this review is to elucidate our working hypothesis that an individual‘s risk or resilience to neuroinflammatory disorders and poor cognitive aging may critically depend on their early life experience, which can change immune reactivity within the brain for the remainder of the lifespan. For instance, early-life infection in rats can profoundly disrupt memory function in young adulthood, as well as accelerate age-related cognitive decline, both of which are linked to enduring changes in glial function that occur in response to the initial infection. We discuss these findings within the context of the growing literature on the role of immune molecules and neuroimmune crosstalk in normal brain development. We highlight the intrinsic factors (e.g., chemokines, hormones) that regulate microglial development and their colonization of the embryonic and postnatal brain, and the capacity for disruption or “re-programming” of this crucial process by external events (e.g, stress, infection). An impact on glia, which in turn alters neural development, has the capacity to profoundly impact cognitive and mental health function at all stages of life. PMID:21822589

The impact of microglial activation on blood-brain barrier in brain diseases

PubMed Central

da Fonseca, Anna Carolina Carvalho; Matias, Diana; Garcia, Celina; Amaral, Rackele; Geraldo, Luiz Henrique; Freitas, Catarina; Lima, Flavia Regina Souza

2014-01-01

The blood-brain barrier (BBB), constituted by an extensive network of endothelial cells (ECs) together with neurons and glial cells, including microglia, forms the neurovascular unit (NVU). The crosstalk between these cells guarantees a proper environment for brain function. In this context, changes in the endothelium-microglia interactions are associated with a variety of inflammation-related diseases in brain, where BBB permeability is compromised. Increasing evidences indicate that activated microglia modulate expression of tight junctions, which are essential for BBB integrity and function. On the other hand, the endothelium can regulate the state of microglial activation. Here, we review recent advances that provide insights into interactions between the microglia and the vascular system in brain diseases such as infectious/inflammatory diseases, epilepsy, ischemic stroke and neurodegenerative disorders. PMID:25404894

Brain transcriptome perturbations in the Hfe(-/-) mouse model of genetic iron loading.

PubMed

Johnstone, Daniel; Graham, Ross M; Trinder, Debbie; Delima, Roheeth D; Riveros, Carlos; Olynyk, John K; Scott, Rodney J; Moscato, Pablo; Milward, Elizabeth A

2012-04-11

Severe disruption of brain iron homeostasis can cause fatal neurodegenerative disease, however debate surrounds the neurologic effects of milder, more common iron loading disorders such as hereditary hemochromatosis, which is usually caused by loss-of-function polymorphisms in the HFE gene. There is evidence from both human and animal studies that HFE gene variants may affect brain function and modify risks of brain disease. To investigate how disruption of HFE influences brain transcript levels, we used microarray and real-time reverse transcription polymerase chain reaction to assess the brain transcriptome in Hfe(-/-) mice relative to wildtype AKR controls (age 10 weeks, n≥4/group). The Hfe(-/-) mouse brain showed numerous significant changes in transcript levels (p<0.05) although few of these related to proteins directly involved in iron homeostasis. There were robust changes of at least 2-fold in levels of transcripts for prominent genes relating to transcriptional regulation (FBJ osteosarcoma oncogene Fos, early growth response genes), neurotransmission (glutamate NMDA receptor Grin1, GABA receptor Gabbr1) and synaptic plasticity and memory (calcium/calmodulin-dependent protein kinase IIα Camk2a). As previously reported for dietary iron-supplemented mice, there were altered levels of transcripts for genes linked to neuronal ceroid lipofuscinosis, a disease characterized by excessive lipofuscin deposition. Labile iron is known to enhance lipofuscin generation which may accelerate brain aging. The findings provide evidence that iron loading disorders can considerably perturb levels of transcripts for genes essential for normal brain function and may help explain some of the neurologic signs and symptoms reported in hemochromatosis patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Detecting number processing and mental calculation in patients with disorders of consciousness using a hybrid brain-computer interface system.

PubMed

Li, Yuanqing; Pan, Jiahui; He, Yanbin; Wang, Fei; Laureys, Steven; Xie, Qiuyou; Yu, Ronghao

2015-12-15

For patients with disorders of consciousness such as coma, a vegetative state or a minimally conscious state, one challenge is to detect and assess the residual cognitive functions in their brains. Number processing and mental calculation are important brain functions but are difficult to detect in patients with disorders of consciousness using motor response-based clinical assessment scales such as the Coma Recovery Scale-Revised due to the patients' motor impairments and inability to provide sufficient motor responses for number- and calculation-based communication. In this study, we presented a hybrid brain-computer interface that combines P300 and steady state visual evoked potentials to detect number processing and mental calculation in Han Chinese patients with disorders of consciousness. Eleven patients with disorders of consciousness who were in a vegetative state (n = 6) or in a minimally conscious state (n = 3) or who emerged from a minimally conscious state (n = 2) participated in the brain-computer interface-based experiment. During the experiment, the patients with disorders of consciousness were instructed to perform three tasks, i.e., number recognition, number comparison, and mental calculation, including addition and subtraction. In each experimental trial, an arithmetic problem was first presented. Next, two number buttons, only one of which was the correct answer to the problem, flickered at different frequencies to evoke steady state visual evoked potentials, while the frames of the two buttons flashed in a random order to evoke P300 potentials. The patients needed to focus on the target number button (the correct answer). Finally, the brain-computer interface system detected P300 and steady state visual evoked potentials to determine the button to which the patients attended, further presenting the results as feedback. Two of the six patients who were in a vegetative state, one of the three patients who were in a minimally conscious state, and the two patients that emerged from a minimally conscious state achieved accuracies significantly greater than the chance level. Furthermore, P300 potentials and steady state visual evoked potentials were observed in the electroencephalography signals from the five patients. Number processing and arithmetic abilities as well as command following were demonstrated in the five patients. Furthermore, our results suggested that through brain-computer interface systems, many cognitive experiments may be conducted in patients with disorders of consciousness, although they cannot provide sufficient behavioral responses.

[Neuropsychological models of autism spectrum disorders - behavioral evidence and functional imaging].

PubMed

Dziobek, Isabel; Bölte, Sven

2011-03-01

To review neuropsychological models of theory of mind (ToM), executive functions (EF), and central coherence (CC) as framework for cognitive abnormalities in autism spectrum disorders (ASD). Behavioral and functional imaging studies are described that assess social-cognitive, emotional, and executive functions as well as locally oriented perception in ASD. Impairments in ToM and EF as well as alterations in CC are frequently replicated phenomena in ASD. Especially problems concerning social perception and ToM have high explanatory value for clinical symptomatology. Brain activation patterns differ between individuals with and without ASD for ToM, EF, und CC functions. An approach focussing on reduced cortical connectivity seems to be increasingly favored over explanations focussing on single affected brain sites. A better understanding of the complexities of ASD in future research demands the integration of clinical, neuropsychological, functional imaging, and molecular genetics evidence. Weaknesses in ToM and EF as well as strengths in detail-focussed perception should be used for individual intervention planning.

A compensatory role for declarative memory in neurodevelopmental disorders

PubMed Central

Ullman, Michael T.; Pullman, Mariel Y.

2015-01-01

Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional, and because this system can learn and retain numerous types of information, functions, and tasks, it should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. PMID:25597655

The Immune System and Developmental Programming of Brain and Behavior

PubMed Central

Bilbo, Staci D.; Schwarz, Jaclyn M.

2012-01-01

The brain, endocrine, and immune systems are inextricably linked. Immune molecules have a powerful impact on neuroendocrine function, including hormone-behavior interactions, during health as well as sickness. Similarly, alterations in hormones, such as during stress, can powerfully impact immune function or reactivity. These functional shifts are evolved, adaptive responses that organize changes in behavior and mobilize immune resources, but can also lead to pathology or exacerbate disease if prolonged or exaggerated. The developing brain in particular is exquisitely sensitive to both endogenous and exogenous signals, and increasing evidence suggests the immune system has a critical role in brain development and associated behavioral outcomes for the life of the individual. Indeed, there are associations between many neuropsychiatric disorders and immune dysfunction, with a distinct etiology in neurodevelopment. The goal of this review is to describe the important role of the immune system during brain development, and to discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, mood and cognition. PMID:22982535

Measurement and Analysis of Olfactory Responses with the Aim of Establishing an Objective Diagnostic Method for Central Olfactory Disorders

NASA Astrophysics Data System (ADS)

Uno, Tominori; Wang, Li-Qun; Miwakeichi, Fumikazu; Tonoike, Mitsuo; Kaneda, Teruo

In order to establish a new diagnostic method for central olfactory disorders and to identify objective indicators, we measured and analyzed brain activities in the parahippocampal gyrus and uncus, region of responsibility for central olfactory disorders. The relationship between olfactory stimulation and brain response at region of responsibility can be examined in terms of fitted responses (FR). FR in these regions may be individual indicators of changes in brain olfactory responses. In the present study, in order to non-invasively and objectively measure olfactory responses, an odor oddball task was conducted on four healthy volunteers using functional magnetic resonance imaging (fMRI) and a odorant stimulator with blast-method. The results showed favorable FR and activation in the parahippocampal gyrus or uncus in all subjects. In some subjects, both the parahippocampal gyrus and uncus were activated. Furthermore, activation was also confirmed in the cingulate gyrus, middle frontal gyrus, precentral gyrus, postcentral gyrus, superior temporal gyrus and insula. The hippocampus and uncus are known to be involved in the olfactory disorders associated with early-stage Alzheimer's disease and other olfactory disorders. In the future, it will be necessary to further develop the present measurement and analysis method to clarify the relationship between central olfactory disorders and brain activities and establish objective indicators that are useful for diagnosis.

Tool use in left brain damage and Alzheimer's disease: What about function and manipulation knowledge?

PubMed

Jarry, Christophe; Osiurak, François; Besnard, Jérémy; Baumard, Josselin; Lesourd, Mathieu; Croisile, Bernard; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Le Gall, Didier

2016-03-01

Tool use disorders are usually associated with difficulties in retrieving function and manipulation knowledge. Here, we investigate tool use (Real Tool Use, RTU), function (Functional Association, FA) and manipulation knowledge (Gesture Recognition, GR) in 17 left-brain-damaged (LBD) patients and 14 AD patients (Alzheimer disease). LBD group exhibited predicted deficit on RTU but not on FA and GR while AD patients showed deficits on GR and FA with preserved tool use skills. These findings question the role played by function and manipulation knowledge in actual tool use. © 2016 The British Psychological Society.

Spatiotemporal psychopathology I: No rest for the brain's resting state activity in depression? Spatiotemporal psychopathology of depressive symptoms.

PubMed

Northoff, Georg

2016-01-15

Despite intense neurobiological investigation in psychiatric disorders like major depressive disorder (MDD), the basic disturbance that underlies the psychopathological symptoms of MDD remains, nevertheless, unclear. Neuroimaging has focused mainly on the brain's extrinsic activity, specifically task-evoked or stimulus-induced activity, as related to the various sensorimotor, affective, cognitive, and social functions. Recently, the focus has shifted to the brain's intrinsic activity, otherwise known as its resting state activity. While various abnormalities have been observed during this activity, their meaning and significance for depression, along with its various psychopathological symptoms, are yet to be defined. Based on findings in healthy brain resting state activity and its particular spatial and temporal structure - defined in a functional and physiological sense rather than anatomical and structural - I claim that the various depressive symptoms are spatiotemporal disturbances of the resting state activity and its spatiotemporal structure. This is supported by recent findings that link ruminations and increased self-focus in depression to abnormal spatial organization of resting state activity. Analogously, affective and cognitive symptoms like anhedonia, suicidal ideation, and thought disorder can be traced to an increased focus on the past, increased past-focus as basic temporal disturbance o the resting state. Based on these findings, I conclude that the various depressive symptoms must be conceived as spatiotemporal disturbances of the brain's resting state's activity and its spatiotemporal structure. Importantly, this entails a new form of psychopathology, "Spatiotemporal Psychopathology" that directly links the brain and psyche, therefore having major diagnostic and therapeutic implications for clinical practice. Copyright © 2015 Elsevier B.V. All rights reserved.

Altered Whole-Brain and Network-Based Functional Connectivity in Parkinson's Disease.

PubMed

de Schipper, Laura J; Hafkemeijer, Anne; van der Grond, Jeroen; Marinus, Johan; Henselmans, Johanna M L; van Hilten, Jacobus J

2018-01-01

Background: Functional imaging methods, such as resting-state functional magnetic resonance imaging, reflect changes in neural connectivity and may help to assess the widespread consequences of disease-specific network changes in Parkinson's disease. In this study we used a relatively new graph analysis approach in functional imaging: eigenvector centrality mapping. This model-free method, applied to all voxels in the brain, identifies prominent regions in the brain network hierarchy and detects localized differences between patient populations. In other neurological disorders, eigenvector centrality mapping has been linked to changes in functional connectivity in certain nodes of brain networks. Objectives: Examining changes in functional brain connectivity architecture on a whole brain and network level in patients with Parkinson's disease. Methods: Whole brain resting-state functional architecture was studied with a recently introduced graph analysis approach (eigenvector centrality mapping). Functional connectivity was further investigated in relation to eight known resting-state networks. Cross-sectional analyses included group comparison of functional connectivity measures of Parkinson's disease patients ( n = 107) with control subjects ( n = 58) and correlations with clinical data, including motor and cognitive impairment and a composite measure of predominantly non-dopaminergic symptoms. Results: Eigenvector centrality mapping revealed that frontoparietal regions were more prominent in the whole-brain network function in patients compared to control subjects, while frontal and occipital brain areas were less prominent in patients. Using standard resting-state networks, we found predominantly increased functional connectivity, namely within sensorimotor system and visual networks in patients. Regional group differences in functional connectivity of both techniques between patients and control subjects partly overlapped for highly connected posterior brain regions, in particular in the posterior cingulate cortex and precuneus. Clinico-functional imaging relations were not found. Conclusions: Changes on the level of functional brain connectivity architecture might provide a different perspective of pathological consequences of Parkinson's disease. The involvement of specific, highly connected (hub) brain regions may influence whole brain functional network architecture in Parkinson's disease.

ALL OUR SONS: THE DEVELOPMENTAL NEUROBIOLOGY AND NEUROENDOCRINOLOGY OF BOYS AT RISK.

PubMed

Schore, Allan N

2017-01-01

Why are boys at risk? To address this question, I use the perspective of regulation theory to offer a model of the deeper psychoneurobiological mechanisms that underlie the vulnerability of the developing male. The central thesis of this work dictates that significant gender differences are seen between male and female social and emotional functions in the earliest stages of development, and that these result from not only differences in sex hormones and social experiences but also in rates of male and female brain maturation, specifically in the early developing right brain. I present interdisciplinary research which indicates that the stress-regulating circuits of the male brain mature more slowly than those of the female in the prenatal, perinatal, and postnatal critical periods, and that this differential structural maturation is reflected in normal gender differences in right-brain attachment functions. Due to this maturational delay, developing males also are more vulnerable over a longer period of time to stressors in the social environment (attachment trauma) and toxins in the physical environment (endocrine disruptors) that negatively impact right-brain development. In terms of differences in gender-related psychopathology, I describe the early developmental neuroendocrinological and neurobiological mechanisms that are involved in the increased vulnerability of males to autism, early onset schizophrenia, attention deficit hyperactivity disorder, and conduct disorders as well as the epigenetic mechanisms that can account for the recent widespread increase of these disorders in U.S. culture. I also offer a clinical formulation of early assessments of boys at risk, discuss the impact of early childcare on male psychopathogenesis, and end with a neurobiological model of optimal adult male socioemotional functions. © 2017 Michigan Association for Infant Mental Health.

Neurotechnology: a new approach for treating brain disorders.

PubMed

Robson, John A; Davenport, R John

2014-05-01

Advances in neuroscience, engineering and computer technologies are creating opportunities to connect the brain directly to devices to treat a variety of disorders, both neurological and psychiatric. They are opening a new field of neuroscience called "neurotechnology." This article reviews efforts in this area that are ongoing at Brown University and the hospitals affiliated with Brown's Alpert Medical School. Two general approaches are being used. One uses advanced electrodes to "sense" the activity of many individual neurons in the cerebral cortex and then use that activity for therapeutic purposes. The other uses various types of devices to stimulate specific networks in the brain in order to restore normal function and alleviate symptoms.