Values: Understanding Written Language and the Mind through Brain Biology.

ERIC Educational Resources Information Center

Brand, Alice G.

Suggesting that neuroscience and the actualities of brain circuitry can provide guidance for what is misunderstood in writing education, namely, the role of subjectivity and values in the composing process, this paper argues that neuroscience provides corporeal evidence for the salience of particular brain structures and processes responsible for…

Insights into Brain Glycogen Metabolism

PubMed Central

Mathieu, Cécile; de la Sierra-Gallay, Ines Li; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2016-01-01

Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. PMID:27402852

Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child.

PubMed

Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

2015-01-01

Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters.

Analysis of the time-varying energy of brain responses to an oddball paradigm using short-term smoothed Wigner-Ville distribution.

PubMed

Tağluk, M E; Cakmak, E D; Karakaş, S

2005-04-30

Cognitive brain responses to external stimuli, as measured by event related potentials (ERPs), have been analyzed from a variety of perspectives to investigate brain dynamics. Here, the brain responses of healthy subjects to auditory oddball paradigms, standard and deviant stimuli, recorded on an Fz electrode site were studied using a short-term version of the smoothed Wigner-Ville distribution (STSW) method. A smoothing kernel was designed to preserve the auto energy of the signal with maximum time and frequency resolutions. Analysis was conducted mainly on the time-frequency distributions (TFDs) of sweeps recorded during successive trials including the TFD of averaged single sweeps as the evoked time-frequency (ETF) brain response and the average of TFDs of single sweeps as the time-frequency (TF) brain response. Also the power entropy and the phase angles of the signal at frequency f and time t locked to the stimulus onset were studied across single trials as the TF power-locked and the TF phase-locked brain responses, respectively. TFDs represented in this way demonstrated the ERP spectro-temporal characteristics from multiple perspectives. The time-varying energy of the individual components manifested interesting TF structures in the form of amplitude modulated (AM) and frequency modulated (FM) energy bursts. The TF power-locked and phase-locked brain responses provoked ERP energies in a manner modulated by cognitive functions, an observation requiring further investigation. These results may lead to a better understanding of integrative brain dynamics.

Experimental Traumatic Brain Injury Results in Long-Term Recovery of Functional Responsiveness in Sensory Cortex but Persisting Structural Changes and Sensorimotor, Cognitive, and Emotional Deficits.

PubMed

Johnstone, Victoria P A; Wright, David K; Wong, Kendrew; O'Brien, Terence J; Rajan, Ramesh; Shultz, Sandy R

2015-09-01

Traumatic brain injury (TBI) is a leading cause of death worldwide. In recent studies, we have shown that experimental TBI caused an immediate (24-h post) suppression of neuronal processing, especially in supragranular cortical layers. We now examine the long-term effects of experimental TBI on the sensory cortex and how these changes may contribute to a range of TBI morbidities. Adult male Sprague-Dawley rats received either a moderate lateral fluid percussion injury (n=14) or a sham surgery (n=12) and 12 weeks of recovery before behavioral assessment, magnetic resonance imaging, and electrophysiological recordings from the barrel cortex. TBI rats demonstrated sensorimotor deficits, cognitive impairments, and anxiety-like behavior, and this was associated with significant atrophy of the barrel cortex and other brain structures. Extracellular recordings from ipsilateral barrel cortex revealed normal neuronal responsiveness and diffusion tensor MRI showed increased fractional anisotropy, axial diffusivity, and tract density within this region. These findings suggest that long-term recovery of neuronal responsiveness is owing to structural reorganization within this region. Therefore, it is likely that long-term structural and functional changes within sensory cortex post-TBI may allow for recovery of neuronal responsiveness, but that this recovery does not remediate all behavioral deficits.

Aggression, the Prequel: Preventing the Need

ERIC Educational Resources Information Center

Gartrell, Dan

2011-01-01

An authority on neuroscience (the study of the structure and functioning of the brain) and human relationships, Daniel Siegel (2001) begins his classic work, "The Developing Mind: How Relationships and the Brain Interact to Shape Who We Are," with a basic concept: the brain is an open system that physically changes throughout life in response to…

Neuroimaging of child abuse: a critical review

PubMed Central

Hart, Heledd; Rubia, Katya

2012-01-01

Childhood maltreatment is a stressor that can lead to the development of behavior problems and affect brain structure and function. This review summarizes the current evidence for the effects of childhood maltreatment on behavior, cognition and the brain in adults and children. Neuropsychological studies suggest an association between child abuse and deficits in IQ, memory, working memory, attention, response inhibition and emotion discrimination. Structural neuroimaging studies provide evidence for deficits in brain volume, gray and white matter of several regions, most prominently the dorsolateral and ventromedial prefrontal cortex but also hippocampus, amygdala, and corpus callosum (CC). Diffusion tensor imaging (DTI) studies show evidence for deficits in structural interregional connectivity between these areas, suggesting neural network abnormalities. Functional imaging studies support this evidence by reporting atypical activation in the same brain regions during response inhibition, working memory, and emotion processing. There are, however, several limitations of the abuse research literature which are discussed, most prominently the lack of control for co-morbid psychiatric disorders, which make it difficult to disentangle which of the above effects are due to maltreatment, the associated psychiatric conditions or a combination or interaction between both. Overall, the better controlled studies that show a direct correlation between childhood abuse and brain measures suggest that the most prominent deficits associated with early childhood abuse are in the function and structure of lateral and ventromedial fronto-limbic brain areas and networks that mediate behavioral and affect control. Future, large scale multimodal neuroimaging studies in medication-naïve subjects, however, are needed that control for psychiatric co-morbidities in order to elucidate the structural and functional brain sequelae that are associated with early environmental adversity, independently of secondary co-morbid conditions. PMID:22457645

Modifications in astrocyte morphology and calcium signaling induced by a brain capillary endothelial cell line.

PubMed

Yoder, Elizabeth J

2002-04-15

Astrocytes extend specialized endfoot processes to perisynaptic and perivascular regions, and thus are positioned to mediate the bidirectional flow of metabolic, ionic, and other transmissive substances between neurons and the blood stream. While mutual structural and functional interactions between neurons and astrocytes have been documented, less is known about the interactions between astrocytes and cerebrovascular cells. For example, although the ability of astrocytes to induce structural and functional changes in endothelial cells is established, the reciprocity of brain endothelial cells to induce changes in astrocytes is undetermined. This issue is addressed in the present study. Changes in primary cultures of neonatal mouse cortical astrocytes were investigated following their coculture with mouse brain capillary endothelial (bEnd3) cells. The presence of bEnd3 cells altered the morphology of astrocytes by transforming them from confluent monolayers into networks of elongated multicellular columns. These columns did not occur when either bEnd3 cells or astrocytes were cocultured with other cell types, suggesting that astrocytes undergo specific morphological consequences when placed in close proximity to brain endothelial cells. In addition to these structural changes, the pharmacological profile of astrocytes was modified by coculture with bEnd3 cells. Astrocytes in the cocultures showed an increased Ca2+ responsiveness to bradykinin and glutamate, but no change in responsiveness to ATP, as compared to controls. Coculturing the astrocytes with a neuronal cell line resulted in increased responsiveness of the glial responses to glutamate but not to bradykinin. These studies indicate that brain endothelial cells induce changes in astrocyte morphology and pharmacology. Copyright 2002 Wiley-Liss, Inc.

The neural processing of hierarchical structure in music and speech at different timescales.

PubMed

Farbood, Morwaread M; Heeger, David J; Marcus, Gary; Hasson, Uri; Lerner, Yulia

2015-01-01

Music, like speech, is a complex auditory signal that contains structures at multiple timescales, and as such is a potentially powerful entry point into the question of how the brain integrates complex streams of information. Using an experimental design modeled after previous studies that used scrambled versions of a spoken story (Lerner et al., 2011) and a silent movie (Hasson et al., 2008), we investigate whether listeners perceive hierarchical structure in music beyond short (~6 s) time windows and whether there is cortical overlap between music and language processing at multiple timescales. Experienced pianists were presented with an extended musical excerpt scrambled at multiple timescales-by measure, phrase, and section-while measuring brain activity with functional magnetic resonance imaging (fMRI). The reliability of evoked activity, as quantified by inter-subject correlation of the fMRI responses, was measured. We found that response reliability depended systematically on musical structure coherence, revealing a topographically organized hierarchy of processing timescales. Early auditory areas (at the bottom of the hierarchy) responded reliably in all conditions. For brain areas at the top of the hierarchy, the original (unscrambled) excerpt evoked more reliable responses than any of the scrambled excerpts, indicating that these brain areas process long-timescale musical structures, on the order of minutes. The topography of processing timescales was analogous with that reported previously for speech, but the timescale gradients for music and speech overlapped with one another only partially, suggesting that temporally analogous structures-words/measures, sentences/musical phrases, paragraph/sections-are processed separately.

The neurobiology of pain, affect and hypnosis.

PubMed

Feldman, Jeffrey B

2004-01-01

Recent neuroimaging studies have used hypnotic suggestion to distinguish the brain structures most associated with the sensory and affective dimensions of pain. This paper reviews studies that delineate the overlapping brain circuits involved in the processing of pain and emotions, and their relationship to autonomic arousal. Also examined are the replicated findings of reliable changes in the activation of specific brain structures and the deactivation of others associated with the induction of hypnosis. These differ from those parts of the brain involved in response to hypnotic suggestions. It is proposed that the activation of a portion of the prefrontal cortex in response to both hypnotic suggestions for decreased pain and to positive emotional experience might indicate a more general underlying mechanism. Great potential exists for further research to clarify the relationships among individual differences in reactivity to pain, emotion, and stress, and the possible role of such differences in the development of chronic pain.

The CLAIR model: Extension of Brodmann areas based on brain oscillations and connectivity.

PubMed

Başar, Erol; Düzgün, Aysel

2016-05-01

Since the beginning of the last century, the localization of brain function has been represented by Brodmann areas, maps of the anatomic organization of the brain. They are used to broadly represent cortical structures with their given sensory-cognitive functions. In recent decades, the analysis of brain oscillations has become important in the correlation of brain functions. Moreover, spectral connectivity can provide further information on the dynamic connectivity between various structures. In addition, brain responses are dynamic in nature and structural localization is almost impossible, according to Luria (1966). Therefore, brain functions are very difficult to localize; hence, a combined analysis of oscillation and event-related coherences is required. In this study, a model termed as "CLAIR" is described to enrich and possibly replace the concept of the Brodmann areas. A CLAIR model with optimum function may take several years to develop, but this study sets out to lay its foundation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Computational Morphometry for Detecting Changes in Brain Structure Due to Development, Aging, Learning, Disease and Evolution

PubMed Central

Mietchen, Daniel; Gaser, Christian

2009-01-01

The brain, like any living tissue, is constantly changing in response to genetic and environmental cues and their interaction, leading to changes in brain function and structure, many of which are now in reach of neuroimaging techniques. Computational morphometry on the basis of Magnetic Resonance (MR) images has become the method of choice for studying macroscopic changes of brain structure across time scales. Thanks to computational advances and sophisticated study designs, both the minimal extent of change necessary for detection and, consequently, the minimal periods over which such changes can be detected have been reduced considerably during the last few years. On the other hand, the growing availability of MR images of more and more diverse brain populations also allows more detailed inferences about brain changes that occur over larger time scales, way beyond the duration of an average research project. On this basis, a whole range of issues concerning the structures and functions of the brain are now becoming addressable, thereby providing ample challenges and opportunities for further contributions from neuroinformatics to our understanding of the brain and how it changes over a lifetime and in the course of evolution. PMID:19707517

Atrophy of spared gray matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke.

PubMed

Gauthier, Lynne V; Taub, Edward; Mark, Victor W; Barghi, Ameen; Uswatte, Gitendra

2012-02-01

Although the motor deficit after stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to constraint-induced movement therapy in patients with chronic stroke may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Voxel-based morphometry analysis was performed on MRI scans from 80 patients with chronic stroke to investigate whether variations in gray matter density were correlated with extent of residual motor impairment or with constraint-induced movement therapy-induced motor recovery. Decreased gray matter density in noninfarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced gray matter density in multiple remote brain regions predicted a lesser extent of motor improvement from constraint-induced movement therapy. Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke.

Atrophy of spared grey matter tissue predicts poorer motor recovery and rehabilitation response in chronic stroke

PubMed Central

Gauthier, Lynne V.; Taub, Edward; Mark, Victor W.; Barghi, Ameen; Uswatte, Gitendra

2011-01-01

Background and Purpose Although the motor deficit following stroke is clearly due to the structural brain damage that has been sustained, this relationship is attenuated from the acute to chronic phases. We investigated the possibility that motor impairment and response to Constraint-Induced Movement therapy (CI therapy) in chronic stroke patients may relate more strongly to the structural integrity of brain structures remote from the lesion than to measures of overt tissue damage. Methods Voxel-based morphometry (VBM) analysis was performed on MRI scans from 80 chronic stroke patients to investigate whether variations in grey matter density were correlated with extent of residual motor impairment or with CI therapy-induced motor recovery. Results Decreased grey matter density in non-infarcted motor regions was significantly correlated with magnitude of residual motor deficit. In addition, reduced grey matter density in multiple remote brain regions predicted a lesser extent of motor improvement from CI therapy. Conclusions Atrophy in seemingly healthy parts of the brain that are distant from the infarct accounts for at least a portion of the sustained motor deficit in chronic stroke. PMID:22096036

Early- and Late-Onset Depression in Late Life: A Prospective Study on Clinical and Structural Brain Characteristics and Response to Electroconvulsive Therapy.

PubMed

Dols, Annemiek; Bouckaert, Filip; Sienaert, Pascal; Rhebergen, Didi; Vansteelandt, Kristof; Ten Kate, Mara; de Winter, Francois-Laurent; Comijs, Hannie C; Emsell, Louise; Oudega, Mardien L; van Exel, Eric; Schouws, Sigfried; Obbels, Jasmien; Wattjes, Mike; Barkhof, Frederik; Eikelenboom, Piet; Vandenbulcke, Mathieu; Stek, Max L

2017-02-01

The clinical profile of late-life depression (LLD) is frequently associated with cognitive impairment, aging-related brain changes, and somatic comorbidity. This two-site naturalistic longitudinal study aimed to explore differences in clinical and brain characteristics and response to electroconvulsive therapy (ECT) in early- (EOD) versus late-onset (LOD) late-life depression (respectively onset <55 and ≥55 years). Between January 2011 and December 2013, 110 patients aged 55 years and older with ECT-treated unipolar depression were included in The Mood Disorders in Elderly treated with ECT study. Clinical profile and somatic health were assessed. Magnetic resonance imaging (MRI) scans were performed before the first ECT and visually rated. Response rate was 78.2% and similar between the two sites but significantly higher in LOD compared with EOD (86.9 versus 67.3%). Clinical, somatic, and brain characteristics were not different between EOD and LOD. Response to ECT was associated with late age at onset and presence of psychotic symptoms and not with structural MRI characteristics. In EOD only, the odds for a higher response were associated with a shorter index episode. The clinical profile, somatic comorbidities, and brain characteristics in LLD were similar in EOD and LOD. Nevertheless, patients with LOD showed a superior response to ECT compared with patients with EOD. Our results indicate that ECT is very effective in LLD, even in vascular burdened patients. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Vision's Brain.

ERIC Educational Resources Information Center

Miller, Julie Ann

1978-01-01

The functional architecture of the primary visual cortex has been explored by monitoring the responses of individual brain cells to visual stimuli. A combination of anatomical and physiological techniques reveals groups of functionally related cells, juxtaposed and superimposed, in a sometimes complex, but presumably efficient, structure. (BB)

Analysis of evoked deep brain connectivity.

PubMed

Klimeš, Petr; Janeček, Jiři; Jurák, Pavel; Halámek, Josef; Chládek, Han; Brázdil, Milan

2013-01-01

Establishing dependencies and connectivity among different structures in the human brain is an extremely complex issue. Methods that are often used for connectivity analysis are based on correlation mechanisms. Correlation methods can analyze changes in signal shape or instantaneous power level. Although recent studies imply that observation of results from both groups of methods together can disclose some of the basic functions and behavior of the human brain during mental activity and decision-making, there is no technique covering changes in the shape of signals along with changes in their power levels. We present a method using a time evaluation of the correlation along with a comparison of power levels in every available contact pair from intracranial electrodes placed in deep brain structures. Observing shape changes in signals after stimulation together with their power levels provides us with new information about signal character between different structures in the brain during task-related events - visual stimulation with motor response. The results for a subject with 95 intracerebral contacts used in this paper demonstrate a clear methodology capable of spatially analyzing connectivity among deep brain structures.

Neuropeptide Signaling Networks and Brain Circuit Plasticity.

PubMed

McClard, Cynthia K; Arenkiel, Benjamin R

2018-01-01

The brain is a remarkable network of circuits dedicated to sensory integration, perception, and response. The computational power of the brain is estimated to dwarf that of most modern supercomputers, but perhaps its most fascinating capability is to structurally refine itself in response to experience. In the language of computers, the brain is loaded with programs that encode when and how to alter its own hardware. This programmed "plasticity" is a critical mechanism by which the brain shapes behavior to adapt to changing environments. The expansive array of molecular commands that help execute this programming is beginning to emerge. Notably, several neuropeptide transmitters, previously best characterized for their roles in hypothalamic endocrine regulation, have increasingly been recognized for mediating activity-dependent refinement of local brain circuits. Here, we discuss recent discoveries that reveal how local signaling by corticotropin-releasing hormone reshapes mouse olfactory bulb circuits in response to activity and further explore how other local neuropeptide networks may function toward similar ends.

Effects of the Variation in Brain Tissue Mechanical Properties on the Intracranial Response of a 6-Year-Old Child

PubMed Central

Cui, Shihai; Li, Haiyan; Li, Xiangnan; Ruan, Jesse

2015-01-01

Brain tissue mechanical properties are of importance to investigate child head injury using finite element (FE) method. However, these properties used in child head FE model normally vary in a large range in published literatures because of the insufficient child cadaver experiments. In this work, a head FE model with detailed anatomical structures is developed from the computed tomography (CT) data of a 6-year-old healthy child head. The effects of brain tissue mechanical properties on traumatic brain response are also analyzed by reconstruction of a head impact on engine hood according to Euro-NCAP testing regulation using FE method. The result showed that the variations of brain tissue mechanical parameters in linear viscoelastic constitutive model had different influences on the intracranial response. Furthermore, the opposite trend was obtained in the predicted shear stress and shear strain of brain tissues caused by the variations of mentioned parameters. PMID:26495031

The neural processing of hierarchical structure in music and speech at different timescales

PubMed Central

Farbood, Morwaread M.; Heeger, David J.; Marcus, Gary; Hasson, Uri; Lerner, Yulia

2015-01-01

Music, like speech, is a complex auditory signal that contains structures at multiple timescales, and as such is a potentially powerful entry point into the question of how the brain integrates complex streams of information. Using an experimental design modeled after previous studies that used scrambled versions of a spoken story (Lerner et al., 2011) and a silent movie (Hasson et al., 2008), we investigate whether listeners perceive hierarchical structure in music beyond short (~6 s) time windows and whether there is cortical overlap between music and language processing at multiple timescales. Experienced pianists were presented with an extended musical excerpt scrambled at multiple timescales—by measure, phrase, and section—while measuring brain activity with functional magnetic resonance imaging (fMRI). The reliability of evoked activity, as quantified by inter-subject correlation of the fMRI responses, was measured. We found that response reliability depended systematically on musical structure coherence, revealing a topographically organized hierarchy of processing timescales. Early auditory areas (at the bottom of the hierarchy) responded reliably in all conditions. For brain areas at the top of the hierarchy, the original (unscrambled) excerpt evoked more reliable responses than any of the scrambled excerpts, indicating that these brain areas process long-timescale musical structures, on the order of minutes. The topography of processing timescales was analogous with that reported previously for speech, but the timescale gradients for music and speech overlapped with one another only partially, suggesting that temporally analogous structures—words/measures, sentences/musical phrases, paragraph/sections—are processed separately. PMID:26029037

Anatomical and functional overlap within the insula and anterior cingulate cortex during interoception and phobic symptom provocation.

PubMed

Caseras, Xavier; Murphy, Kevin; Mataix-Cols, David; López-Solà, Marina; Soriano-Mas, Carles; Ortriz, Hector; Pujol, Jesus; Torrubia, Rafael

2013-05-01

The anterior insula and the dorsal anterior cingulate cortex (ACC) are regarded as key brain structures associated with the integration of perceived phobic characteristics of external stimuli and the perception of ones own body responses that leads to emotional feelings. To test to what extent the activity in these two brain structures anatomically and functionally overlap during phobic reactions and interoception, we submitted the same group of phobic participants (n = 29; either spider or blood-injection-injury (BII) phobics) and controls (n = 17) to both type of experimental paradigms. Results showed that there was a clear anatomical overlap in the Blood Oxygen Level-Dependent (BOLD) responses within the anterior insula and ACC elicited during phobic symptom provocation and during interoceptive awareness. The activity within these two brain structures also showed to be correlated in the spider phobia group, but not in the BII phobic participants. Our results seem to support the idea that the activity within these two brain areas would be associated with the integration of perceived stimuli characteristics and bodily responses that lead to what we label as "fear." However, that seems not to be the case in BII phobia, where more research is needed in order to clarify to what extent that could be associated with the idiosyncratic physiological response that these patients present in front of phobic stimuli (i.e., drop in heart rate and blood pressure). Copyright © 2011 Wiley Periodicals, Inc.

Violations of information structure: an electrophysiological study of answers to wh-questions.

PubMed

Cowles, H W; Kluender, Robert; Kutas, Marta; Polinsky, Maria

2007-09-01

This study investigates brain responses to violations of information structure in wh-question-answer pairs, with particular emphasis on violations of focus assignment in it-clefts (It was the queen that silenced the banker). Two types of ERP responses in answers to wh-questions were found. First, all words in the focus-marking (cleft) position elicited a large positivity (P3b) characteristic of sentence-final constituents, as did the final words of these sentences, which suggests that focused elements may trigger integration effects like those seen at sentence end. Second, the focusing of an inappropriate referent elicited a smaller, N400-like effect. The results show that comprehenders actively use structural focus cues and discourse-level restrictions during online sentence processing. These results, based on visual stimuli, were different from the brain response to auditory focus violations indicated by pitch-accent [Hruska, C., Steinhauer, K., Alter, K., & Steube, A. (2000). ERP effects of sentence accents and violations of the information structure. In Poster presented at the 13th annual CUNY conference on human sentence processing, San Diego, CA.], but similar to brain responses to newly introduced discourse referents [Bornkessel, I., Schlesewsky, M., & Friederici, A. (2003). Contextual information modulated initial processes of syntactic integration: the role of inter- versus intrasentential predictions. Journal of Experimental Psychology: Learning, Memory and Cognition, 29, 871-882.].

The Human Nervous System: A Framework for Teaching and the Teaching Brain

ERIC Educational Resources Information Center

Rodriguez, Vanessa

2013-01-01

The teaching brain is a new concept that mirrors the complex, dynamic, and context-dependent nature of the learning brain. In this article, I use the structure of the human nervous system and its sensing, processing, and responding components as a framework for a re-conceptualized teaching system. This teaching system is capable of responses on an…

Predictive Feedback Can Account for Biphasic Responses in the Lateral Geniculate Nucleus

PubMed Central

Jehee, Janneke F. M.; Ballard, Dana H.

2009-01-01

Biphasic neural response properties, where the optimal stimulus for driving a neural response changes from one stimulus pattern to the opposite stimulus pattern over short periods of time, have been described in several visual areas, including lateral geniculate nucleus (LGN), primary visual cortex (V1), and middle temporal area (MT). We describe a hierarchical model of predictive coding and simulations that capture these temporal variations in neuronal response properties. We focus on the LGN-V1 circuit and find that after training on natural images the model exhibits the brain's LGN-V1 connectivity structure, in which the structure of V1 receptive fields is linked to the spatial alignment and properties of center-surround cells in the LGN. In addition, the spatio-temporal response profile of LGN model neurons is biphasic in structure, resembling the biphasic response structure of neurons in cat LGN. Moreover, the model displays a specific pattern of influence of feedback, where LGN receptive fields that are aligned over a simple cell receptive field zone of the same polarity decrease their responses while neurons of opposite polarity increase their responses with feedback. This phase-reversed pattern of influence was recently observed in neurophysiology. These results corroborate the idea that predictive feedback is a general coding strategy in the brain. PMID:19412529

Optical manipulation for optogenetics: otoliths manipulation in zebrafish (Conference Presentation)

NASA Astrophysics Data System (ADS)

Favre-Bulle, Itia A.; Scott, Ethan; Rubinsztein-Dunlop, Halina

2016-03-01

Otoliths play an important role in Zebrafish in terms of hearing and sense of balance. Many studies have been conducted to understand its structure and function, however the encoding of its movement in the brain remains unknown. Here we developed a noninvasive system capable of manipulating the otolith using optical trapping while we image its behavioral response and brain activity. We'll also present our tools for behavioral response detection and brain activity mapping. Acceleration is sensed through movements of the otoliths in the inner ear. Because experimental manipulations involve movements, electrophysiology and fluorescence microscopy are difficult. As a result, the neural codes underlying acceleration sensation are poorly understood. We have developed a technique for optically trapping otoliths, allowing us to simulate acceleration in stationary larval zebrafish. By applying forces to the otoliths, we can elicit behavioral responses consistent with compensation for perceived acceleration. Since the animal is stationary, we can use calcium imaging in these animals' brains to identify the functional circuits responsible for mediating responses to acceleration in natural settings.

Age-related reduction of adaptive brain response during semantic integration is associated with gray matter reduction.

PubMed

Zhu, Zude; Yang, Fengjun; Li, Dongning; Zhou, Lianjun; Liu, Ying; Zhang, Ying; Chen, Xuezhi

2017-01-01

While aging is associated with increased knowledge, it is also associated with decreased semantic integration. To investigate brain activation changes during semantic integration, a sample of forty-eight 25-75 year-old adults read sentences with high cloze (HC) and low cloze (LC) probability while functional magnetic resonance imaging was conducted. Significant age-related reduction of cloze effect (LC vs. HC) was found in several regions, especially the left middle frontal gyrus (MFG) and right inferior frontal gyrus (IFG), which play an important role in semantic integration. Moreover, when accounting for global gray matter volume reduction, the age-cloze correlation in the left MFG and right IFG was absent. The results suggest that brain structural atrophy may disrupt brain response in aging brains, which then show less brain engagement in semantic integration.

Inter-subject synchronization of brain responses during natural music listening

PubMed Central

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

2015-01-01

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

The multi-modal responses of a physical head model subjected to various blast exposure conditions

NASA Astrophysics Data System (ADS)

Ouellet, S.; Philippens, M.

2018-01-01

The local and global biomechanical response of the body to a blast wave is the first step of a sequence that leads to the development of stresses and strains which can exceed the tolerance of brain tissue. These stresses and strains may then lead to neuro-physical changes in the brain and contribute to initiate a cascade of events leading to injury. The specific biomechanical pathways by which the blast energy is transmitted through the head structure are, however, not clearly understood. Multiple transmission mechanisms have been proposed to explain the generation of brain stresses following the impingement of a blast wave on the head. With the use of a physical head model, the work presented here aims at demonstrating that the proposed transmission mechanisms are not mutually exclusive. They are part of a continuum of head responses where, depending on the exposure conditions, a given mechanism may or may not dominate. This article presents the joint analysis of previous blast test results generated with the brain injury protection evaluation device (BIPED) headform under four significantly different exposure conditions. The focus of the analysis is to demonstrate how the nature of the recorded response is highly dependent on the exposure characteristics and consequently, on the method used to reproduce blast exposure in a laboratory environment. The timing and magnitude of the variations in intra-cranial pressures (ICP) were analysed relative to the external pressure field in order to better understand the wave dynamics occurring within the brain structure of the headform. ICP waveforms were also analysed in terms of their energy spectral density to better identify the energy partitioning between the different modes of response. It is shown that the BIPED response is multi-modal and that the energy partitioning between its different modes of response is greatly influenced by exposure characteristics such as external peak overpressure, impulse, blast wave structure, and direction of propagation. Convincing evidence of stresses generated from local skull deformation is presented along with evidence of stress transmission through relative brain-to-skull motion. These findings suggest that research aimed at defining exposure thresholds should not focus on a single stress transmission mechanism or use experimental designs unrepresentative of realistic blast loading conditions that may favour a given mechanism over another.

Neural signatures of cognitive and emotional biases in depression

PubMed Central

Fossati, Philippe

2008-01-01

Functional brain imaging studies suggest that depression is a system-level disorder affecting discrete but functionally linked cortical and limbic structures, with abnormalities in the anterior cingulate, lateral, ami medial prefrontal cortex, amygdala, ami hippocampus. Within this circuitry, abnormal corticolimbic interactions underlie cognitive deficits ami emotional impairment in depression. Depression involves biases toward processing negative emotional information and abnormal self-focus in response to emotional stimuli. These biases in depression could reflect excessive analytical self-focus in depression, as well as impaired cognitive control of emotional response to negative stimuli. By combining structural and functional investigations, brain imaging studies mav help to generate novel antidepressant treatments that regulate structural and factional plasticity within the neural network regulating mood and affective behavior.

Structural brain aging and speech production: a surface-based brain morphometry study.

PubMed

Tremblay, Pascale; Deschamps, Isabelle

2016-07-01

While there has been a growing number of studies examining the neurofunctional correlates of speech production over the past decade, the neurostructural correlates of this immensely important human behaviour remain less well understood, despite the fact that previous studies have established links between brain structure and behaviour, including speech and language. In the present study, we thus examined, for the first time, the relationship between surface-based cortical thickness (CT) and three different behavioural indexes of sublexical speech production: response duration, reaction times and articulatory accuracy, in healthy young and older adults during the production of simple and complex meaningless sequences of syllables (e.g., /pa-pa-pa/ vs. /pa-ta-ka/). The results show that each behavioural speech measure was sensitive to the complexity of the sequences, as indicated by slower reaction times, longer response durations and decreased articulatory accuracy in both groups for the complex sequences. Older adults produced longer speech responses, particularly during the production of complex sequence. Unique age-independent and age-dependent relationships between brain structure and each of these behavioural measures were found in several cortical and subcortical regions known for their involvement in speech production, including the bilateral anterior insula, the left primary motor area, the rostral supramarginal gyrus, the right inferior frontal sulcus, the bilateral putamen and caudate, and in some region less typically associated with speech production, such as the posterior cingulate cortex.

Development, Validation and Parametric study of a 3-Year-Old Child Head Finite Element Model

NASA Astrophysics Data System (ADS)

Cui, Shihai; Chen, Yue; Li, Haiyan; Ruan, ShiJie

2015-12-01

Traumatic brain injury caused by drop and traffic accidents is an important reason for children's death and disability. Recently, the computer finite element (FE) head model has been developed to investigate brain injury mechanism and biomechanical responses. Based on CT data of a healthy 3-year-old child head, the FE head model with detailed anatomical structure was developed. The deep brain structures such as white matter, gray matter, cerebral ventricle, hippocampus, were firstly created in this FE model. The FE model was validated by comparing the simulation results with that of cadaver experiments based on reconstructing the child and adult cadaver experiments. In addition, the effects of skull stiffness on the child head dynamic responses were further investigated. All the simulation results confirmed the good biofidelity of the FE model.

Functional divisions for visual processing in the central brain of flying Drosophila

PubMed Central

Weir, Peter T.; Dickinson, Michael H.

2015-01-01

Although anatomy is often the first step in assigning functions to neural structures, it is not always clear whether architecturally distinct regions of the brain correspond to operational units. Whereas neuroarchitecture remains relatively static, functional connectivity may change almost instantaneously according to behavioral context. We imaged panneuronal responses to visual stimuli in a highly conserved central brain region in the fruit fly, Drosophila, during flight. In one substructure, the fan-shaped body, automated analysis revealed three layers that were unresponsive in quiescent flies but became responsive to visual stimuli when the animal was flying. The responses of these regions to a broad suite of visual stimuli suggest that they are involved in the regulation of flight heading. To identify the cell types that underlie these responses, we imaged activity in sets of genetically defined neurons with arborizations in the targeted layers. The responses of this collection during flight also segregated into three sets, confirming the existence of three layers, and they collectively accounted for the panneuronal activity. Our results provide an atlas of flight-gated visual responses in a central brain circuit. PMID:26324910

Functional divisions for visual processing in the central brain of flying Drosophila.

PubMed

Weir, Peter T; Dickinson, Michael H

2015-10-06

Although anatomy is often the first step in assigning functions to neural structures, it is not always clear whether architecturally distinct regions of the brain correspond to operational units. Whereas neuroarchitecture remains relatively static, functional connectivity may change almost instantaneously according to behavioral context. We imaged panneuronal responses to visual stimuli in a highly conserved central brain region in the fruit fly, Drosophila, during flight. In one substructure, the fan-shaped body, automated analysis revealed three layers that were unresponsive in quiescent flies but became responsive to visual stimuli when the animal was flying. The responses of these regions to a broad suite of visual stimuli suggest that they are involved in the regulation of flight heading. To identify the cell types that underlie these responses, we imaged activity in sets of genetically defined neurons with arborizations in the targeted layers. The responses of this collection during flight also segregated into three sets, confirming the existence of three layers, and they collectively accounted for the panneuronal activity. Our results provide an atlas of flight-gated visual responses in a central brain circuit.

Technological Advances and the Study of Reading.

ERIC Educational Resources Information Center

Henk, William A.

Recent technological advances in neuroanatomy and neurophysiology have unearthed structural and functional patterns in the brain that can be associated with severe reading disabilities. As a response, this paper examines several computer-driven technologies whose capabilities shed light on brain-related issues germane to reading, with the intent…

Postoperative Structural Brain Changes and Cognitive Dysfunction in Patients with Breast Cancer.

PubMed

Sato, Chiho; Sekiguchi, Atsushi; Kawai, Masaaki; Kotozaki, Yuka; Nouchi, Rui; Tada, Hiroshi; Takeuchi, Hikaru; Ishida, Takanori; Taki, Yasuyuki; Kawashima, Ryuta; Ohuchi, Noriaki

2015-01-01

The primary purpose of this study was to clarify the influence of the early response to surgery on brain structure and cognitive function in patients with breast cancer. It was hypothesized that the structure of the thalamus would change during the early response after surgery due to the effects of anesthesia and would represent one aspect of an intermediate phenotype of postoperative cognitive dysfunction (POCD). We examined 32 postmenopausal females with breast cancer and 20 age-matched controls. We assessed their cognitive function (attention, memory, and executive function), and performed brain structural MRI 1.5 ± 0.5 days before and 5.6 ± 1.2 days after surgery. We found a significant interaction between regional grey matter volume (rGMV) in the thalamus (P < 0.05, familywise error (FWE), small volume correction (SVC)) and one attention domain subtest (P = 0.001, Bonferroni correction) after surgery in the patient group compared with the control group. Furthermore, the changes in attention were significantly associated with sevoflurane anesthetic dose (r2 = 0.247, β = ‒0.471, P = 0.032) and marginally associated with rGMV changes in the thalamus (P = 0.07, FWE, SVC) in the Pt group. Our findings suggest that alterations in brain structure, particularly in the thalamus, may occur shortly after surgery and may be associated with attentional dysfunction. This early postoperative response to anesthesia may represent an intermediate phenotype of POCD. It was assumed that patients experiencing other risk factors of POCD, such as the severity of surgery, the occurrence of complications, and pre-existing cognitive impairments, would develop clinical POCD with broad and multiple types of cognitive dysfunction.

Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain.

PubMed

Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

2015-01-01

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS.

Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain

PubMed Central

Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

2015-01-01

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653

Selective Activation of Resting-State Networks following Focal Stimulation in a Connectome-Based Network Model of the Human Brain

PubMed Central

2016-01-01

Abstract When the brain is stimulated, for example, by sensory inputs or goal-oriented tasks, the brain initially responds with activities in specific areas. The subsequent pattern formation of functional networks is constrained by the structural connectivity (SC) of the brain. The extent to which information is processed over short- or long-range SC is unclear. Whole-brain models based on long-range axonal connections, for example, can partly describe measured functional connectivity dynamics at rest. Here, we study the effect of SC on the network response to stimulation. We use a human whole-brain network model comprising long- and short-range connections. We systematically activate each cortical or thalamic area, and investigate the network response as a function of its short- and long-range SC. We show that when the brain is operating at the edge of criticality, stimulation causes a cascade of network recruitments, collapsing onto a smaller space that is partly constrained by SC. We found both short- and long-range SC essential to reproduce experimental results. In particular, the stimulation of specific areas results in the activation of one or more resting-state networks. We suggest that the stimulus-induced brain activity, which may indicate information and cognitive processing, follows specific routes imposed by structural networks explaining the emergence of functional networks. We provide a lookup table linking stimulation targets and functional network activations, which potentially can be useful in diagnostics and treatments with brain stimulation. PMID:27752540

Hemodynamic and morphologic responses in mouse brain during acute head injury imaged by multispectral structured illumination

NASA Astrophysics Data System (ADS)

Volkov, Boris; Mathews, Marlon S.; Abookasis, David

2015-03-01

Multispectral imaging has received significant attention over the last decade as it integrates spectroscopy, imaging, tomography analysis concurrently to acquire both spatial and spectral information from biological tissue. In the present study, a multispectral setup based on projection of structured illumination at several near-infrared wavelengths and at different spatial frequencies is applied to quantitatively assess brain function before, during, and after the onset of traumatic brain injury in an intact mouse brain (n=5). For the production of head injury, we used the weight drop method where weight of a cylindrical metallic rod falling along a metal tube strikes the mouse's head. Structured light was projected onto the scalp surface and diffuse reflected light was recorded by a CCD camera positioned perpendicular to the mouse head. Following data analysis, we were able to concurrently show a series of hemodynamic and morphologic changes over time including higher deoxyhemoglobin, reduction in oxygen saturation, cell swelling, etc., in comparison with baseline measurements. Overall, results demonstrates the capability of multispectral imaging based structured illumination to detect and map of brain tissue optical and physiological properties following brain injury in a simple noninvasive and noncontact manner.

Exploring the motivational brain: effects of implicit power motivation on brain activation in response to facial expressions of emotion.

PubMed

Schultheiss, Oliver C; Wirth, Michelle M; Waugh, Christian E; Stanton, Steven J; Meier, Elizabeth A; Reuter-Lorenz, Patricia

2008-12-01

This study tested the hypothesis that implicit power motivation (nPower), in interaction with power incentives, influences activation of brain systems mediating motivation. Twelve individuals low (lowest quartile) and 12 individuals high (highest quartile) in nPower, as assessed per content coding of picture stories, were selected from a larger initial participant pool and participated in a functional magnetic resonance imaging study during which they viewed high-dominance (angry faces), low-dominance (surprised faces) and control stimuli (neutral faces, gray squares) under oddball-task conditions. Consistent with hypotheses, high-power participants showed stronger activation in response to emotional faces in brain structures involved in emotion and motivation (insula, dorsal striatum, orbitofrontal cortex) than low-power participants.

Violations of Information Structure: An Electrophysiological Study of Answers to Wh-Questions

ERIC Educational Resources Information Center

Cowles, H. W.; Kluender, Robert; Kutas, Marta; Polinsky, Maria

2007-01-01

This study investigates brain responses to violations of information structure in wh-question-answer pairs, with particular emphasis on violations of focus assignment in it-clefts (It was the queen that silenced the banker). Two types of ERP responses in answers to wh-questions were found. First, all words in the focus-marking (cleft) position…

Her versus his migraine: multiple sex differences in brain function and structure

PubMed Central

Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

2012-01-01

Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a ‘sex phenotype’ in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs. PMID:22843414

Her versus his migraine: multiple sex differences in brain function and structure.

PubMed

Maleki, Nasim; Linnman, Clas; Brawn, Jennifer; Burstein, Rami; Becerra, Lino; Borsook, David

2012-08-01

Migraine is twice as common in females as in males, but the mechanisms behind this difference are still poorly understood. We used high-field magnetic resonance imaging in male and female age-matched interictal (migraine free) migraineurs and matched healthy controls to determine alterations in brain structure. Female migraineurs had thicker posterior insula and precuneus cortices compared with male migraineurs and healthy controls of both sexes. Furthermore, evaluation of functional responses to heat within the migraine groups indicated concurrent functional differences in male and female migraineurs and a sex-specific pattern of functional connectivity of these two regions with the rest of the brain. The results support the notion of a 'sex phenotype' in migraine and indicate that brains are differentially affected by migraine in females compared with males. Furthermore, the results also support the notion that sex differences involve both brain structure as well as functional circuits, in that emotional circuitry compared with sensory processing appears involved to a greater degree in female than male migraineurs.

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

PubMed

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

2013-05-01

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

Effect of brain structure, brain function, and brain connectivity on relapse in alcohol-dependent patients.

PubMed

Beck, Anne; Wüstenberg, Torsten; Genauck, Alexander; Wrase, Jana; Schlagenhauf, Florian; Smolka, Michael N; Mann, Karl; Heinz, Andreas

2012-08-01

In alcohol-dependent patients, brain atrophy and functional brain activation elicited by alcohol-associated stimuli may predict relapse. However, to date, the interaction between both factors has not been studied. To determine whether results from structural and functional magnetic resonance imaging are associated with relapse in detoxified alcohol-dependent patients. A cue-reactivity functional magnetic resonance experiment with alcohol-associated and neutral stimuli. After a follow-up period of 3 months, the group of 46 detoxified alcohol-dependent patients was subdivided into 16 abstainers and 30 relapsers. Faculty for Clinical Medicine Mannheim at the University of Heidelberg, Germany. A total of 46 detoxified alcohol-dependent patients and 46 age- and sex-matched healthy control subjects Local gray matter volume, local stimulus-related functional magnetic resonance imaging activation, joint analyses of structural and functional data with Biological Parametric Mapping, and connectivity analyses adopting the psychophysiological interaction approach. Subsequent relapsers showed pronounced atrophy in the bilateral orbitofrontal cortex and in the right medial prefrontal and anterior cingulate cortex, compared with healthy controls and patients who remained abstinent. The local gray matter volume-corrected brain response elicited by alcohol-associated vs neutral stimuli in the left medial prefrontal cortex was enhanced for subsequent relapsers, whereas abstainers displayed an increased neural response in the midbrain (the ventral tegmental area extending into the subthalamic nucleus) and ventral striatum. For alcohol-associated vs neutral stimuli in abstainers compared with relapsers, the analyses of the psychophysiological interaction showed a stronger functional connectivity between the midbrain and the left amygdala and between the midbrain and the left orbitofrontal cortex. Subsequent relapsers displayed increased brain atrophy in brain areas associated with error monitoring and behavioral control. Correcting for gray matter reductions, we found that, in these patients, alcohol-related cues elicited increased activation in brain areas associated with attentional bias toward these cues and that, in patients who remained abstinent, increased activation and connectivity were observed in brain areas associated with processing of salient or aversive stimuli.

Catecholamines and cognition after traumatic brain injury

PubMed Central

Jenkins, Peter O.; Mehta, Mitul A.

2016-01-01

Abstract Cognitive problems are one of the main causes of ongoing disability after traumatic brain injury. The heterogeneity of the injuries sustained and the variability of the resulting cognitive deficits makes treating these problems difficult. Identifying the underlying pathology allows a targeted treatment approach aimed at cognitive enhancement. For example, damage to neuromodulatory neurotransmitter systems is common after traumatic brain injury and is an important cause of cognitive impairment. Here, we discuss the evidence implicating disruption of the catecholamines (dopamine and noradrenaline) and review the efficacy of catecholaminergic drugs in treating post-traumatic brain injury cognitive impairments. The response to these therapies is often variable, a likely consequence of the heterogeneous patterns of injury as well as a non-linear relationship between catecholamine levels and cognitive functions. This individual variability means that measuring the structure and function of a person’s catecholaminergic systems is likely to allow more refined therapy. Advanced structural and molecular imaging techniques offer the potential to identify disruption to the catecholaminergic systems and to provide a direct measure of catecholamine levels. In addition, measures of structural and functional connectivity can be used to identify common patterns of injury and to measure the functioning of brain ‘networks’ that are important for normal cognitive functioning. As the catecholamine systems modulate these cognitive networks, these measures could potentially be used to stratify treatment selection and monitor response to treatment in a more sophisticated manner. PMID:27256296

Longitudinal Structural and Functional Brain Network Alterations in a Mouse Model of Neuropathic Pain.

PubMed

Bilbao, Ainhoa; Falfán-Melgoza, Claudia; Leixner, Sarah; Becker, Robert; Singaravelu, Sathish Kumar; Sack, Markus; Sartorius, Alexander; Spanagel, Rainer; Weber-Fahr, Wolfgang

2018-04-22

Neuropathic pain affects multiple brain functions, including motivational processing. However, little is known about the structural and functional brain changes involved in the transition from an acute to a chronic pain state. Here we combined behavioral phenotyping of pain thresholds with multimodal neuroimaging to longitudinally monitor changes in brain metabolism, structure and connectivity using the spared nerve injury (SNI) mouse model of chronic neuropathic pain. We investigated stimulus-evoked pain responses prior to SNI surgery, and one and twelve weeks following surgery. A progressive development and potentiation of stimulus-evoked pain responses (cold and mechanical allodynia) were detected during the course of pain chronification. Voxel-based morphometry demonstrated striking decreases in volume following pain induction in all brain sites assessed - an effect that reversed over time. Similarly, all global and local network changes that occurred following pain induction disappeared over time, with two notable exceptions: the nucleus accumbens, which played a more dominant role in the global network in a chronic pain state and the prefrontal cortex and hippocampus, which showed lower connectivity. These changes in connectivity were accompanied by enhanced glutamate levels in the hippocampus, but not in the prefrontal cortex. We suggest that hippocampal hyperexcitability may contribute to alterations in synaptic plasticity within the nucleus accumbens, and to pain chronification. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Interventional programmes to improve cognition during healthy and pathological ageing: Cortical modulations and evidence for brain plasticity.

PubMed

Cespón, Jesús; Miniussi, Carlo; Pellicciari, Maria Concetta

2018-05-01

A growing body of evidence suggests that healthy elderly individuals and patients with Alzheimer's disease retain an important potential for neuroplasticity. This review summarizes studies investigating the modulation of neural activity and structural brain integrity in response to interventions involving cognitive training, physical exercise and non-invasive brain stimulation in healthy elderly and cognitively impaired subjects (including patients with mild cognitive impairment (MCI) and Alzheimer's disease). Moreover, given the clinical relevance of neuroplasticity, we discuss how evidence for neuroplasticity can be inferred from the functional and structural brain changes observed after implementing these interventions. We emphasize that multimodal programmes, which combine several types of interventions, improve cognitive function to a greater extent than programmes that use a single interventional approach. We suggest specific methods for weighting the relative importance of cognitive training, physical exercise and non-invasive brain stimulation according to the functional and structural state of the brain of the targeted subject to maximize the cognitive improvements induced by multimodal programmes. Copyright © 2018 Elsevier B.V. All rights reserved.

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

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

PubMed

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

2007-07-17

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

Different brains process numbers differently: structural bases of individual differences in spatial and nonspatial number representations.

PubMed

Krause, Florian; Lindemann, Oliver; Toni, Ivan; Bekkering, Harold

2014-04-01

A dominant hypothesis on how the brain processes numerical size proposes a spatial representation of numbers as positions on a "mental number line." An alternative hypothesis considers numbers as elements of a generalized representation of sensorimotor-related magnitude, which is not obligatorily spatial. Here we show that individuals' relative use of spatial and nonspatial representations has a cerebral counterpart in the structural organization of the posterior parietal cortex. Interindividual variability in the linkage between numbers and spatial responses (faster left responses to small numbers and right responses to large numbers; spatial-numerical association of response codes effect) correlated with variations in gray matter volume around the right precuneus. Conversely, differences in the disposition to link numbers to force production (faster soft responses to small numbers and hard responses to large numbers) were related to gray matter volume in the left angular gyrus. This finding suggests that numerical cognition relies on multiple mental representations of analogue magnitude using different neural implementations that are linked to individual traits.

A dynamic in vivo-like organotypic blood-brain barrier model to probe metastatic brain tumors

NASA Astrophysics Data System (ADS)

Xu, Hui; Li, Zhongyu; Yu, Yue; Sizdahkhani, Saman; Ho, Winson S.; Yin, Fangchao; Wang, Li; Zhu, Guoli; Zhang, Min; Jiang, Lei; Zhuang, Zhengping; Qin, Jianhua

2016-11-01

The blood-brain barrier (BBB) restricts the uptake of many neuro-therapeutic molecules, presenting a formidable hurdle to drug development in brain diseases. We proposed a new and dynamic in vivo-like three-dimensional microfluidic system that replicates the key structural, functional and mechanical properties of the blood-brain barrier in vivo. Multiple factors in this system work synergistically to accentuate BBB-specific attributes-permitting the analysis of complex organ-level responses in both normal and pathological microenvironments in brain tumors. The complex BBB microenvironment is reproduced in this system via physical cell-cell interaction, vascular mechanical cues and cell migration. This model possesses the unique capability to examine brain metastasis of human lung, breast and melanoma cells and their therapeutic responses to chemotherapy. The results suggest that the interactions between cancer cells and astrocytes in BBB microenvironment might affect the ability of malignant brain tumors to traverse between brain and vascular compartments. Furthermore, quantification of spatially resolved barrier functions exists within a single assay, providing a versatile and valuable platform for pharmaceutical development, drug testing and neuroscientific research.

The "chicken-and-egg" development of political opinions.

PubMed

Beattie, Peter

2017-01-01

Twin studies have revealed political ideology to be partially heritable. Neurological research has shown that ideological differences are reflected in brain structure and response, suggesting a direct genotype-phenotype link. Social and informational environments, however, also demonstrably affect brain structure and response. This leads to a "chicken-and-egg" question: do genes produce brains with ideological predispositions, causing the preferential absorption of consonant information and thereby forming an ideology, or do social and informational environments do most of the heavy lifting, with genetic evidence the spurious artifact of outdated methodology? Or are both inextricably intertwined contributors? This article investigates the relative contributions of genetic and environmental factors to ideological development using a role-play experiment investigating the development of opinions on a novel political issue. The results support the view that the process is bidirectional, suggesting that, like most traits, political ideology is produced by the complex interplay of genetic and (social/informational) environmental influences.

Machine learning approaches for integrating clinical and imaging features in late-life depression classification and response prediction.

PubMed

Patel, Meenal J; Andreescu, Carmen; Price, Julie C; Edelman, Kathryn L; Reynolds, Charles F; Aizenstein, Howard J

2015-10-01

Currently, depression diagnosis relies primarily on behavioral symptoms and signs, and treatment is guided by trial and error instead of evaluating associated underlying brain characteristics. Unlike past studies, we attempted to estimate accurate prediction models for late-life depression diagnosis and treatment response using multiple machine learning methods with inputs of multi-modal imaging and non-imaging whole brain and network-based features. Late-life depression patients (medicated post-recruitment) (n = 33) and older non-depressed individuals (n = 35) were recruited. Their demographics and cognitive ability scores were recorded, and brain characteristics were acquired using multi-modal magnetic resonance imaging pretreatment. Linear and nonlinear learning methods were tested for estimating accurate prediction models. A learning method called alternating decision trees estimated the most accurate prediction models for late-life depression diagnosis (87.27% accuracy) and treatment response (89.47% accuracy). The diagnosis model included measures of age, Mini-mental state examination score, and structural imaging (e.g. whole brain atrophy and global white mater hyperintensity burden). The treatment response model included measures of structural and functional connectivity. Combinations of multi-modal imaging and/or non-imaging measures may help better predict late-life depression diagnosis and treatment response. As a preliminary observation, we speculate that the results may also suggest that different underlying brain characteristics defined by multi-modal imaging measures-rather than region-based differences-are associated with depression versus depression recovery because to our knowledge this is the first depression study to accurately predict both using the same approach. These findings may help better understand late-life depression and identify preliminary steps toward personalized late-life depression treatment. Copyright © 2015 John Wiley & Sons, Ltd.

The grammar of visual narrative: Neural evidence for constituent structure in sequential image comprehension.

PubMed

Cohn, Neil; Jackendoff, Ray; Holcomb, Phillip J; Kuperberg, Gina R

2014-11-01

Constituent structure has long been established as a central feature of human language. Analogous to how syntax organizes words in sentences, a narrative grammar organizes sequential images into hierarchic constituents. Here we show that the brain draws upon this constituent structure to comprehend wordless visual narratives. We recorded neural responses as participants viewed sequences of visual images (comics strips) in which blank images either disrupted individual narrative constituents or fell at natural constituent boundaries. A disruption of either the first or the second narrative constituent produced a left-lateralized anterior negativity effect between 500 and 700ms. Disruption of the second constituent also elicited a posteriorly-distributed positivity (P600) effect. These neural responses are similar to those associated with structural violations in language and music. These findings provide evidence that comprehenders use a narrative structure to comprehend visual sequences and that the brain engages similar neurocognitive mechanisms to build structure across multiple domains. Copyright © 2014 Elsevier Ltd. All rights reserved.

The grammar of visual narrative: Neural evidence for constituent structure in sequential image comprehension

PubMed Central

Cohn, Neil; Jackendoff, Ray; Holcomb, Phillip J.; Kuperberg, Gina R.

2014-01-01

Constituent structure has long been established as a central feature of human language. Analogous to how syntax organizes words in sentences, a narrative grammar organizes sequential images into hierarchic constituents. Here we show that the brain draws upon this constituent structure to comprehend wordless visual narratives. We recorded neural responses as participants viewed sequences of visual images (comics strips) in which blank images either disrupted individual narrative constituents or fell at natural constituent boundaries. A disruption of either the first or the second narrative constituent produced a left-lateralized anterior negativity effect between 500-700ms. Disruption of the second constituent also elicited a posteriorly-distributed positivity (P600) effect. These neural responses are similar to those associated with structural violations in language and music. These findings provide evidence that comprehenders use a narrative structure to comprehend visual sequences and that the brain engages similar neurocognitive mechanisms to build structure across multiple domains. PMID:25241329

Neuroanatomy of the killer whale (Orcinus orca): a magnetic resonance imaging investigation of structure with insights on function and evolution.

PubMed

Wright, Alexandra; Scadeng, Miriam; Stec, Dominik; Dubowitz, Rebecca; Ridgway, Sam; Leger, Judy St

2017-01-01

The evolutionary process of adaptation to an obligatory aquatic existence dramatically modified cetacean brain structure and function. The brain of the killer whale (Orcinus orca) may be the largest of all taxa supporting a panoply of cognitive, sensory, and sensorimotor abilities. Despite this, examination of the O. orca brain has been limited in scope resulting in significant deficits in knowledge concerning its structure and function. The present study aims to describe the neural organization and potential function of the O. orca brain while linking these traits to potential evolutionary drivers. Magnetic resonance imaging was used for volumetric analysis and three-dimensional reconstruction of an in situ postmortem O. orca brain. Measurements were determined for cortical gray and cerebral white matter, subcortical nuclei, cerebellar gray and white matter, corpus callosum, hippocampi, superior and inferior colliculi, and neuroendocrine structures. With cerebral volume comprising 81.51 % of the total brain volume, this O. orca brain is one of the most corticalized mammalian brains studied to date. O. orca and other delphinoid cetaceans exhibit isometric scaling of cerebral white matter with increasing brain size, a trait that violates an otherwise evolutionarily conserved cerebral scaling law. Using comparative neurobiology, it is argued that the divergent cerebral morphology of delphinoid cetaceans compared to other mammalian taxa may have evolved in response to the sensorimotor demands of the aquatic environment. Furthermore, selective pressures associated with the evolution of echolocation and unihemispheric sleep are implicated in substructure morphology and function. This neuroanatomical dataset, heretofore absent from the literature, provides important quantitative data to test hypotheses regarding brain structure, function, and evolution within Cetacea and across Mammalia.

The human parental brain: In vivo neuroimaging

PubMed Central

Swain, James E.

2015-01-01

Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants’ current and future behavior. Indeed, the parent–infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust—likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimaging studies of the parental brain—from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health. PMID:21036196

An aberrant parasympathetic response: a new perspective linking chronic stress and itch.

PubMed

Kim, Hei Sung; Yosipovitch, Gil

2013-04-01

Perceived stress has long been known to alter the dynamic equilibrium established between the nervous, endocrine and immune system and is widely recognised to trigger or enhance pruritus. However, the exact mechanism of how the major stress response systems, such as the hypothalamus-pituitary adrenal (HPA) axis and the autonomic nervous system induce or aggravate chronic itch, has not been elucidated. The limbic regions of the brain such as the prefrontal cortex and hippocampus are deeply involved in the regulation of the stress response and intersect with circuits that are responsible for memory and reward. According to the 'Polyvagal Theory', certain limbic structures that serve as a 'higher brain equivalent of the parasympathetic nervous system' play a foremost role in maintaining body homoeostasis by functioning as an active vagal brake. In addition, the limbic system has been postulated to regulate two distinct, yet related aspects of itch: (i) the sensory-discriminative aspect; and (ii) the affective-cognitive aspect. Chronic stress-induced itch is hypothesised to be caused by stress-related changes in limbic structure with subsequent rewiring of both the peripheral and central pruriceptive circuits. Herein, we review data suggesting that a dysfunctional parasympathetic nervous system associated with chronic stress may play a critical role in the regulatory control of key candidate molecules, receptors and brain structures involved in chronic itch. © 2012 John Wiley & Sons A/S.

Influence of sex steroid hormones on the adolescent brain and behavior: An update

PubMed Central

Vigil, Pilar; del Río, Juan Pablo; Carrera, BÁrbara; ArÁnguiz, Florencia C.

2016-01-01

This review explains the main effects exerted by sex steroids and other hormones on the adolescent brain. During the transition from puberty to adolescence, these hormones participate in the organizational phenomena that structurally shape some brain circuits. In adulthood, this will propitiate some specific behavior as responses to the hormones now activating those neural circuits. Adolescence is, then, a critical “organizational window” for the brain to develop adequately, since steroid hormones perform important functions at this stage. For this reason, the adolescent years are very important for future behaviors in human beings. Changes that occur or fail to occur during adolescence will determine behaviors for the rest of one's lifetime. Consequently, understanding the link between adolescent behavior and brain development as influenced by sex steroids and other hormones and compounds is very important in order to interpret various psycho-affective pathologies. Lay Summary: The effect of steroid hormones on the development of the adolescent brain, and therefore, on adolescent behavior, is noticeable. This review presents their main activational and organizational effects. During the transition from puberty to adolescence, organizational phenomena triggered by steroids structurally affect the remodeling of brain circuits. Later in adulthood, these changes will be reflected in behavioral responses to such hormones. Adolescence can then be seen as a fundamental “organizational window” during which sex steroids and other hormones and compounds play relevant roles. The understanding of the relationship between adolescent behavior and the way hormones influence brain development help understand some psychological disorders. PMID:27833209

Brain stimulation-induced neuroplasticity underlying therapeutic response in phantom sounds.

PubMed

Poeppl, Timm B; Langguth, Berthold; Lehner, Astrid; Frodl, Thomas; Rupprecht, Rainer; Kreuzer, Peter M; Landgrebe, Michael; Schecklmann, Martin

2018-01-01

Noninvasive brain stimulation can modify phantom sounds for longer periods by modulating neural activity and putatively inducing regional neuroplastic changes. However, treatment response is limited and there are no good demographic or clinical predictors for treatment outcome. We used state-of-the-art voxel-based morphometry (VBM) to investigate whether transcranial magnetic stimulation-induced neuroplasticity determines therapeutic outcome. Sixty subjects chronically experiencing phantom sounds (i.e., tinnitus) received repetitive transcranial magnetic stimulation (rTMS) of left dorsolateral prefrontal and temporal cortex according to a protocol that has been shown to yield a significantly higher number of treatment responders than sham stimulation and previous stimulation protocols. Structural magnetic resonance imaging was performed before and after rTMS. In VBM whole-brain analyses (P < 0.05, FWE corrected), we assessed longitudinal gray matter changes as well as structural connectivity between the ensuing regions. We observed longitudinal mesoscopic gray matter changes of left dorsolateral prefontal (DLPFC), left operculo-insular, and right inferior temporal cortex (ITC) in responders (N = 22) but not nonresponders (N = 38), as indicated by a group × time interaction and post-hoc tests. These results were neither influenced by age, sex, hearing loss nor by tinnitus laterality, duration, and severity at baseline. Furthermore, we found robust DLPFC-insula and insula-ITC connectivity in responders, while only relatively weak DLPFC-insula connectivity and no insula-ITC connectivity could be demonstrated in nonresponders. Our results reinforce the implication of nonauditory brain regions in phantom sounds and suggest the dependence of therapeutic response on their neuroplastic capabilities. The latter in turn may depend on (differences in) their individual structural connectivity. Hum Brain Mapp 39:554-562, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Cocaine-Induced Structural Plasticity in Input Regions to Distinct Cell Types in Nucleus Accumbens.

PubMed

Barrientos, Cindy; Knowland, Daniel; Wu, Mingche M J; Lilascharoen, Varoth; Huang, Kee Wui; Malenka, Robert C; Lim, Byung Kook

2018-05-09

The nucleus accumbens (NAc) is a brain region implicated in pathological motivated behaviors such as drug addiction and is composed predominantly of two discrete populations of neurons, dopamine receptor-1- and dopamine receptor-2-expressing medium spiny neurons (D1-MSNs and D2-MSNs, respectively). It is unclear whether these populations receive inputs from different brain areas and whether input regions to these cell types undergo distinct structural adaptations in response to the administration of addictive drugs such as cocaine. Using a modified rabies virus-mediated tracing method, we created a comprehensive brain-wide monosynaptic input map to NAc D1- and D2-MSNs. Next, we analyzed nearly 2000 dendrites and 125,000 spines of neurons across four input regions (the prelimbic cortex, medial orbitofrontal cortex, basolateral amygdala, and ventral hippocampus) at four separate time points during cocaine administration and withdrawal to examine changes in spine density in response to repeated intraperitoneal cocaine injection in mice. D1- and D2-MSNs display overall similar input profiles, with the exception that D1-MSNs receive significantly more input from the medial orbitofrontal cortex. We found that neurons in distinct brain areas projecting to D1- and D2-MSNs display different adaptations in dendritic spine density at different stages of cocaine administration and withdrawal. While NAc D1- and D2-MSNs receive input from similar brain structures, cocaine-induced spine density changes in input regions are quite distinct and dynamic. While previous studies have focused on input-specific postsynaptic changes within NAc MSNs in response to cocaine, these findings emphasize the dramatic changes that occur in the afferent input regions as well. Published by Elsevier Inc.

Large-scale brain networks in affective and social neuroscience: Towards an integrative functional architecture of the brain

PubMed Central

Barrett, Lisa Feldman; Satpute, Ajay

2013-01-01

Understanding how a human brain creates a human mind ultimately depends on mapping psychological categories and concepts to physical measurements of neural response. Although it has long been assumed that emotional, social, and cognitive phenomena are realized in the operations of separate brain regions or brain networks, we demonstrate that it is possible to understand the body of neuroimaging evidence using a framework that relies on domain general, distributed structure-function mappings. We review current research in affective and social neuroscience and argue that the emerging science of large-scale intrinsic brain networks provides a coherent framework for a domain-general functional architecture of the human brain. PMID:23352202

Finite element simulations of the head-brain responses to the top impacts of a construction helmet: Effects of the neck and body mass.

PubMed

Wu, John Z; Pan, Christopher S; Wimer, Bryan M; Rosen, Charles L

2017-01-01

Traumatic brain injuries are among the most common severely disabling injuries in the United States. Construction helmets are considered essential personal protective equipment for reducing traumatic brain injury risks at work sites. In this study, we proposed a practical finite element modeling approach that would be suitable for engineers to optimize construction helmet design. The finite element model includes all essential anatomical structures of a human head (i.e. skin, scalp, skull, cerebrospinal fluid, brain, medulla, spinal cord, cervical vertebrae, and discs) and all major engineering components of a construction helmet (i.e. shell and suspension system). The head finite element model has been calibrated using the experimental data in the literature. It is technically difficult to precisely account for the effects of the neck and body mass on the dynamic responses, because the finite element model does not include the entire human body. An approximation approach has been developed to account for the effects of the neck and body mass on the dynamic responses of the head-brain. Using the proposed model, we have calculated the responses of the head-brain during a top impact when wearing a construction helmet. The proposed modeling approach would provide a tool to improve the helmet design on a biomechanical basis.

Effects of severity of traumatic brain injury and brain reserve on cognitive-control related brain activation.

PubMed

Scheibel, Randall S; Newsome, Mary R; Troyanskaya, Maya; Steinberg, Joel L; Goldstein, Felicia C; Mao, Hui; Levin, Harvey S

2009-09-01

Functional magnetic resonance imaging (fMRI) has revealed more extensive cognitive-control related brain activation following traumatic brain injury (TBI), but little is known about how activation varies with TBI severity. Thirty patients with moderate to severe TBI and 10 with orthopedic injury (OI) underwent fMRI at 3 months post-injury using a stimulus response compatibility task. Regression analyses indicated that lower total Glasgow Coma Scale (GCS) and GCS verbal component scores were associated with higher levels of brain activation. Brain-injured patients were also divided into three groups based upon their total GCS score (3-4, 5-8, or 9-15), and patients with a total GCS score of 8 or less produced increased, diffuse activation that included structures thought to mediate visual attention and cognitive control. The cingulate gyrus and thalamus were among the areas showing greatest increases, and this is consistent with vulnerability of these midline structures in severe, diffuse TBI. Better task performance was associated with higher activation, and there were differences in the over-activation pattern that varied with TBI severity, including greater reliance upon left-lateralized brain structures in patients with the most severe injuries. These findings suggest that over-activation is at least partially effective for improving performance and may be compensatory.

Developmental Differences in Error-Related ERPs in Middle- to Late-Adolescent Males

ERIC Educational Resources Information Center

Santesso, Diane L.; Segalowitz, Sidney J.

2008-01-01

Although there are some studies documenting structural brain changes during late adolescence, there are few showing functional brain changes over this period in humans. Of special interest would be functional changes in the medial frontal cortex that reflect response monitoring. In order to examine such age-related differences, the authors…

Impact of sex differences in brain response to infection with Plasmodium berghei.

PubMed

Dkhil, Mohamed A; Al-Shaebi, Esam M; Lubbad, Mahmoud Y; Al-Quraishy, Saleh

2016-01-01

Malaria is considered to be one of the most prevalent diseases in the world. Severity of the disease between males and females is very important in clinical research areas. In this study, we investigated the impact of sex differences in brain response to infection with Plasmodium berghei. Male and female C57Bl/6 mice were infected with P. berghei-infected erythrocytes. The infection induced a significant change in weight loss in males (-7.2 % ± 0.5) than females (-4.9 % ± 0.6). The maximum parasitemia reached about 15 % at day 9 postinfection. Also, P. berghei infection caused histopathological changes in the brain of mice. These changes were in the form of inflammation, hemorrhage, and structural changes in Purkinje cells. In addition, P. berghei was able to induce a marked oxidative damage in mice brain. The infection induced a significant increase in male brain glutathione than females while the brain catalase level was significantly increased in infected females than infected males. Moreover, the change in brain neurotransmitters, dopamine, epinephrine, norepinephrine, and serotonin, was more in infected males than infected females. At the molecular level, P. berghei was able to induce upregulations of Adam23, Cabp1, Cacnb4, Glrb, and Vdac3-mRNA in the brain of mice. These genes were significantly upregulated in infected males than in infected females. In general, P. berghei could induce structural, biochemical, and molecular alterations in mice brain. Severity of these alterations was different according to sex of mice.

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

PubMed

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

2016-04-15

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

Developing Master Keys to Brain Pathology, Cancer and Aging from the Structural Biology of Proteins Controlling Reactive Oxygen Species and DNA Repair

PubMed Central

Perry, J. Jefferson P.; Fan, Li; Tainer, John A.

2007-01-01

This review is focused on proteins with key roles in pathways controlling either reactive oxygen species or DNA damage responses, both of which are essential for preserving the nervous system. An imbalance of reactive oxygen species or inappropriate DNA damage response likely causes mutational or cytotoxic outcomes, which may lead to cancer and/or aging phenotypes. Moreover, individuals with hereditary disorders in proteins of these cellular pathways have significant neurological abnormalities. Mutations in a superoxide dismutase, which removes oxygen free radicals, may cause the neurodegenerative disease amyotrophic lateral sclerosis. Additionally, DNA repair disorders that affect the brain to varying extents include ataxia-telangiectasia-like disorder, Cockayne syndrome or Werner syndrome. Here, we highlight recent advances gained through structural biochemistry studies on enzymes linked to these disorders and other related enzymes acting within the same cellular pathways. We describe the current understanding of how these vital proteins coordinate chemical steps and integrate cellular signaling and response events. Significantly, these structural studies may provide a set of master keys to developing a unified understanding of the survival mechanisms utilized after insults by reactive oxygen species and genotoxic agents, and also provide a basis for developing an informed intervention in brain tumor and neurodegenerative disease progression. PMID:17174478

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal

PubMed Central

Ries, Michele L.; Jabbar, Britta M.; Schmitz, Taylor W.; Trivedi, Mehul A.; Gleason, Carey E.; Carlsson, Cynthia M.; Rowley, Howard A.; Asthana, Sanjay; Johnson, Sterling C.

2009-01-01

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer’s disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants’ activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly-significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD. PMID:17445294

Sleep duration and age-related changes in brain structure and cognitive performance.

PubMed

Lo, June C; Loh, Kep Kee; Zheng, Hui; Sim, Sam K Y; Chee, Michael W L

2014-07-01

To investigate the contribution of sleep duration and quality to age-related changes in brain structure and cognitive performance in relatively healthy older adults. Community-based longitudinal brain and cognitive aging study using a convenience sample. Participants were studied in a research laboratory. Relatively healthy adults aged 55 y and older at study commencement. N/A. Participants underwent magnetic resonance imaging and neuropsychological assessment every 2 y. Subjective assessments of sleep duration and quality and blood samples were obtained. Each hour of reduced sleep duration at baseline augmented the annual expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after controlling for the effects of age, sex, education, and body mass index. In contrast, global sleep quality at baseline did not modulate either brain or cognitive aging. High-sensitivity C-reactive protein, a marker of systemic inflammation, showed no correlation with baseline sleep duration, brain structure, or cognitive performance. In healthy older adults, short sleep duration is associated with greater age-related brain atrophy and cognitive decline. These associations are not associated with elevated inflammatory responses among short sleepers. Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance.

Age and meloxicam modify the response of the glutamate vesicular transporters (VGLUTs) after transient global cerebral ischemia in the rat brain.

PubMed

Llorente, Irene L; Pérez-Rodríguez, Diego; Burgin, Taiana C; Gonzalo-Orden, José M; Martínez-Villayandre, Beatriz; Fernández-López, Arsenio

2013-05-01

This study analyzes how age and inflammation modify the response of the vesicular glutamate transporters (VGLUTs), VGLUT1-3 to global brain ischemia/reperfusion (I/R) in brain areas with different I/R vulnerabilities. Global ischemia was induced in 3- and 18-month-old male Sprague-Dawley rats and CA1 and CA3 hippocampal areas, dentate gyrus and cerebral cortex of sham-operated and I/R animals were removed 48 h after insult. Real-time PCR analysis revealed that I/R challenge resulted in a significant decrease of the VGLUT mRNA levels in young animals. Western blot assays showed a lessened age-dependent response to the ischemic damage in VGLUT1 and VGLUT3, while VGLUT2 presented an age and structure-dependent response to challenge. The use of the anti-inflammatory agent meloxicam following challenge showed that COX2 inhibition promotes the expression of VGLUTs in both sham and injured animals, which results in a lessened response to I/R injury. VGLUT1 and VGLUT3 presented an age-dependent response to ischemic damage, while this VGLUT response was age both and structure-dependent. In addition, COX-2 inhibition resulted in an increase of VGLUT1 and VGLUT2 protein amounts both in sham and injured animals together with a lessening of the transporters' response to ischemia. Copyright © 2013 Elsevier Inc. All rights reserved.

The consequences of fetal growth restriction on brain structure and neurodevelopmental outcome.

PubMed

Miller, Suzanne L; Huppi, Petra S; Mallard, Carina

2016-02-15

Fetal growth restriction (FGR) is a significant complication of pregnancy describing a fetus that does not grow to full potential due to pathological compromise. FGR affects 3-9% of pregnancies in high-income countries, and is a leading cause of perinatal mortality and morbidity. Placental insufficiency is the principal cause of FGR, resulting in chronic fetal hypoxia. This hypoxia induces a fetal adaptive response of cardiac output redistribution to favour vital organs, including the brain, and is in consequence called brain sparing. Despite this, it is now apparent that brain sparing does not ensure normal brain development in growth-restricted fetuses. In this review we have brought together available evidence from human and experimental animal studies to describe the complex changes in brain structure and function that occur as a consequence of FGR. In both humans and animals, neurodevelopmental outcomes are influenced by the timing of the onset of FGR, the severity of FGR, and gestational age at delivery. FGR is broadly associated with reduced total brain volume and altered cortical volume and structure, decreased total number of cells and myelination deficits. Brain connectivity is also impaired, evidenced by neuronal migration deficits, reduced dendritic processes, and less efficient networks with decreased long-range connections. Subsequent to these structural alterations, short- and long-term functional consequences have been described in school children who had FGR, most commonly including problems in motor skills, cognition, memory and neuropsychological dysfunctions. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Segregating the significant from the mundane on a moment-to-moment basis via direct and indirect amygdala contributions

PubMed Central

Lim, Seung-Lark; Padmala, Srikanth; Pessoa, Luiz

2009-01-01

If the amygdala is involved in shaping perceptual experience when affectively significant visual items are encountered, responses in this structure should be correlated with both visual cortex responses and behavioral reports. Here, we investigated how affective significance shapes visual perception during an attentional blink paradigm combined with aversive conditioning. Behaviorally, following aversive learning, affectively significant scenes (CS+) were better detected than neutral (CS−) ones. In terms of mean brain responses, both amygdala and visual cortical responses were stronger during CS+ relative to CS− trials. Increased brain responses in these regions were associated with improved behavioral performance across participants and followed a mediation-like pattern. Importantly, the mediation pattern was observed in a trial-by-trial analysis, revealing that the specific pattern of trial-by-trial variability in brain responses was closely related to single-trial behavioral performance. Furthermore, the influence of the amygdala on visual cortical responses was consistent with a mediation, although partial, via frontal brain regions. Our results thus suggest that affective significance potentially determines the fate of a visual item during competitive interactions by enhancing sensory processing through both direct and indirect paths. In so doing, the amygdala helps separate the significant from the mundane. PMID:19805383

[Effects of the removal of the orbito-frontal cortex on the development of reflex analgesia].

PubMed

Reshetniak, V K; Kukushkin, M L

1989-07-01

The authors studied the effect of electric acupuncture stimulation (EAP) on the changes in pain thresholds prior to and after removal of the orbito-frontal cortex (OFC) of the brain in behavioral experiments on adult cats. Removal of OFC increased the thresholds of pain response at the 4th and the 5th levels of the conventional scale, reflecting emotionally-affective manifestations of pain, and intensified the effect of antinociceptive EAP. The results obtained are analysed in relation to the inhibitory tonic effect of OFC on antinociceptive structures of the brain. Different effects of OFC and somatosensory cortex on the antinociceptive structures of the brain are discussed.

Direct electrical stimulation as an input gate into brain functional networks: principles, advantages and limitations.

PubMed

Mandonnet, Emmanuel; Winkler, Peter A; Duffau, Hugues

2010-02-01

While the fundamental and clinical contribution of direct electrical stimulation (DES) of the brain is now well acknowledged, its advantages and limitations have not been re-evaluated for a long time. Here, we critically review exactly what DES can tell us about cerebral function. First, we show that DES is highly sensitive for detecting the cortical and axonal eloquent structures. Moreover, DES also provides a unique opportunity to study brain connectivity, since each area responsive to stimulation is in fact an input gate into a large-scale network rather than an isolated discrete functional site. DES, however, also has a limitation: its specificity is suboptimal. Indeed, DES may lead to interpretations that a structure is crucial because of the induction of a transient functional response when stimulated, whereas (1) this effect is caused by the backward spreading of the electro-stimulation along the network to an essential area and/or (2) the stimulated region can be functionally compensated owing to long-term brain plasticity mechanisms. In brief, although DES is still the gold standard for brain mapping, its combination with new methods such as perioperative neurofunctional imaging and biomathematical modeling is now mandatory, in order to clearly differentiate those networks that are actually indispensable to function from those that can be compensated.

Connectivity Predicts Deep Brain Stimulation Outcome in Parkinson Disease

PubMed Central

Horn, Andreas; Reich, Martin; Vorwerk, Johannes; Li, Ningfei; Wenzel, Gregor; Fang, Qianqian; Schmitz-Hübsch, Tanja; Nickl, Robert; Kupsch, Andreas; Volkmann, Jens; Kühn, Andrea A.; Fox, Michael D.

2018-01-01

Objective The benefit of deep brain stimulation (DBS) for Parkinson disease (PD) may depend on connectivity between the stimulation site and other brain regions, but which regions and whether connectivity can predict outcome in patients remain unknown. Here, we identify the structural and functional connectivity profile of effective DBS to the subthalamic nucleus (STN) and test its ability to predict outcome in an independent cohort. Methods A training dataset of 51 PD patients with STN DBS was combined with publicly available human connectome data (diffusion tractography and resting state functional connectivity) to identify connections reliably associated with clinical improvement (motor score of the Unified Parkinson Disease Rating Scale [UPDRS]). This connectivity profile was then used to predict outcome in an independent cohort of 44 patients from a different center. Results In the training dataset, connectivity between the DBS electrode and a distributed network of brain regions correlated with clinical response including structural connectivity to supplementary motor area and functional anticorrelation to primary motor cortex (p<0.001). This same connectivity profile predicted response in an independent patient cohort (p<0.01). Structural and functional connectivity were independent predictors of clinical improvement (p<0.001) and estimated response in individual patients with an average error of 15% UPDRS improvement. Results were similar using connectome data from normal subjects or a connectome age, sex, and disease matched to our DBS patients. Interpretation Effective STN DBS for PD is associated with a specific connectivity profile that can predict clinical outcome across independent cohorts. This prediction does not require specialized imaging in PD patients themselves. PMID:28586141

Functional and structural brain correlates of theory of mind and empathy deficits in schizophrenia.

PubMed

Benedetti, Francesco; Bernasconi, Alessandro; Bosia, Marta; Cavallaro, Roberto; Dallaspezia, Sara; Falini, Andrea; Poletti, Sara; Radaelli, Daniele; Riccaboni, Roberta; Scotti, Giuseppe; Smeraldi, Enrico

2009-10-01

Patients affected by schizophrenia show deficits in social cognition, with abnormal performance on tasks targeting theory of mind (ToM) and empathy (Emp). Brain imaging studies suggested that ToM and Emp depend on the activation of brain networks mainly localized at the superior temporal lobe and temporo-parietal junction. Participants included 24 schizophrenia patients and 20 control subjects. We used brain blood oxygen level dependent fMRI to study the neural responses to tasks targeting ToM and Emp. We then studied voxel-based morphometry of grey matter in areas where diagnosis influenced functional activation to both tasks. Outcomes were analyzed in the context of the general linear model, with global grey matter volume as nuisance covariate for structural MRI. Patients showed worse performance on both tasks. We found significant effects of diagnosis on neural responses to the tasks in a wide cluster in right posterior superior temporal lobe (encompassing BA 22-42), in smaller clusters in left temporo-parietal junction and temporal pole (BA 38 and 39), and in a white matter region adjacent to medial prefrontal cortex (BA 10). A pattern of double dissociation of the effects of diagnosis and task on neural responses emerged. Among these areas, grey matter volume was found to be reduced in right superior temporal lobe regions of patients. Functional and structural abnormalities were observed in areas affected by the schizophrenic process early in the illness course, and known to be crucial for social cognition, suggesting a biological basis for social cognition deficits in schizophrenia.

Time-variant fMRI activity in the brainstem and higher structures in response to acupuncture.

PubMed

Napadow, Vitaly; Dhond, Rupali; Park, Kyungmo; Kim, Jieun; Makris, Nikos; Kwong, Kenneth K; Harris, Richard E; Purdon, Patrick L; Kettner, Norman; Hui, Kathleen K S

2009-08-01

Acupuncture modulation of activity in the human brainstem is not well known. This structure is plagued by physiological artifact in neuroimaging experiments. In addition, most studies have used short (<15 min) block designs, which miss delayed responses following longer duration stimulation. We used brainstem-focused cardiac-gated fMRI and evaluated time-variant brain response to longer duration (>30 min) stimulation with verum (VA, electro-stimulation at acupoint ST-36) or sham point (SPA, non-acupoint electro-stimulation) acupuncture. Our results provide evidence that acupuncture modulates brainstem nuclei important to endogenous monoaminergic and opioidergic systems. Specifically, VA modulated activity in the substantia nigra (SN), nucleus raphe magnus, locus ceruleus, nucleus cuneiformis, and periaqueductal gray (PAG). Activation in the ventrolateral PAG was greater for VA compared to SPA. Linearly decreasing time-variant activation, suggesting classical habituation, was found in response to both VA and SPA in sensorimotor (SII, posterior insula, premotor cortex) brain regions. However, VA also produced linearly time-variant activity in limbic regions (amygdala, hippocampus, and SN), which was bimodal and not likely habituation--consisting of activation in early blocks, and deactivation by the end of the run. Thus, acupuncture induces different brain response early, compared to 20-30 min after stimulation. We attribute the fMRI differences between VA and SPA to more varied and stronger psychophysical response induced by VA. Our study demonstrates that acupuncture modulation of brainstem structures can be studied non-invasively in humans, allowing for comparison to animal studies. Our protocol also demonstrates a fMRI approach to study habituation and other time-variant phenomena over longer time durations.

In Vivo Investigation of the Effectiveness of a Hyper-viscoelastic Model in Simulating Brain Retraction

NASA Astrophysics Data System (ADS)

Li, Ping; Wang, Weiwei; Zhang, Chenxi; An, Yong; Song, Zhijian

2016-07-01

Intraoperative brain retraction leads to a misalignment between the intraoperative positions of the brain structures and their previous positions, as determined from preoperative images. In vitro swine brain sample uniaxial tests showed that the mechanical response of brain tissue to compression and extension could be described by the hyper-viscoelasticity theory. The brain retraction caused by the mechanical process is a combination of brain tissue compression and extension. In this paper, we first constructed a hyper-viscoelastic framework based on the extended finite element method (XFEM) to simulate intraoperative brain retraction. To explore its effectiveness, we then applied this framework to an in vivo brain retraction simulation. The simulation strictly followed the clinical scenario, in which seven swine were subjected to brain retraction. Our experimental results showed that the hyper-viscoelastic XFEM framework is capable of simulating intraoperative brain retraction and improving the navigation accuracy of an image-guided neurosurgery system (IGNS).

Sexual selection predicts brain structure in dragon lizards.

PubMed

Hoops, D; Ullmann, J F P; Janke, A L; Vidal-Garcia, M; Stait-Gardner, T; Dwihapsari, Y; Merkling, T; Price, W S; Endler, J A; Whiting, M J; Keogh, J S

2017-02-01

Phenotypic traits such as ornaments and armaments are generally shaped by sexual selection, which often favours larger and more elaborate males compared to females. But can sexual selection also influence the brain? Previous studies in vertebrates report contradictory results with no consistent pattern between variation in brain structure and the strength of sexual selection. We hypothesize that sexual selection will act in a consistent way on two vertebrate brain regions that directly regulate sexual behaviour: the medial preoptic nucleus (MPON) and the ventromedial hypothalamic nucleus (VMN). The MPON regulates male reproductive behaviour whereas the VMN regulates female reproductive behaviour and is also involved in male aggression. To test our hypothesis, we used high-resolution magnetic resonance imaging combined with traditional histology of brains in 14 dragon lizard species of the genus Ctenophorus that vary in the strength of precopulatory sexual selection. Males belonging to species that experience greater sexual selection had a larger MPON and a smaller VMN. Conversely, females did not show any patterns of variation in these brain regions. As the volumes of both these regions also correlated with brain volume (BV) in our models, we tested whether they show the same pattern of evolution in response to changes in BV and found that the do. Therefore, we show that the primary brain nuclei underlying reproductive behaviour in vertebrates can evolve in a mosaic fashion, differently between males and females, likely in response to sexual selection, and that these same regions are simultaneously evolving in concert in relation to overall brain size. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Prefrontal Cortex Structure Predicts Training-Induced Improvements in Multitasking Performance.

PubMed

Verghese, Ashika; Garner, K G; Mattingley, Jason B; Dux, Paul E

2016-03-02

The ability to perform multiple, concurrent tasks efficiently is a much-desired cognitive skill, but one that remains elusive due to the brain's inherent information-processing limitations. Multitasking performance can, however, be greatly improved through cognitive training (Van Selst et al., 1999, Dux et al., 2009). Previous studies have examined how patterns of brain activity change following training (for review, see Kelly and Garavan, 2005). Here, in a large-scale human behavioral and imaging study of 100 healthy adults, we tested whether multitasking training benefits, assessed using a standard dual-task paradigm, are associated with variability in brain structure. We found that the volume of the rostral part of the left dorsolateral prefrontal cortex (DLPFC) predicted an individual's response to training. Critically, this association was observed exclusively in a task-specific training group, and not in an active-training control group. Our findings reveal a link between DLPFC structure and an individual's propensity to gain from training on a task that taps the limits of cognitive control. Cognitive "brain" training is a rapidly growing, multibillion dollar industry (Hayden, 2012) that has been touted as the panacea for a variety of disorders that result in cognitive decline. A key process targeted by such training is "cognitive control." Here, we combined an established cognitive control measure, multitasking ability, with structural brain imaging in a sample of 100 participants. Our goal was to determine whether individual differences in brain structure predict the extent to which people derive measurable benefits from a cognitive training regime. Ours is the first study to identify a structural brain marker-volume of left hemisphere dorsolateral prefrontal cortex-associated with the magnitude of multitasking performance benefits induced by training at an individual level. Copyright © 2016 the authors 0270-6474/16/362638-08$15.00/0.

Canonical Genetic Signatures of the Adult Human Brain

PubMed Central

Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

2015-01-01

The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

The "chicken-and-egg" development of political opinionsThe roles of genes, social status, ideology, and information.

PubMed

Peter, Beattie J D

2017-01-01

Twin studies have revealed political ideology to be partially heritable. Neurological research has shown that ideological differences are reflected in brain structure and response, suggesting a direct genotype-phenotype link. Social and informational environments, however, also demonstrably affect brain structure and response. This leads to a "chicken-and-egg" question: do genes produce brains with ideological predispositions, causing the preferential absorption of consonant information and thereby forming an ideology, or do social and informational environments do most of the heavy lifting, with genetic evidence the spurious artifact of outdated methodology? Or are both inextricably intertwined contributors? This article investigates the relative contributions of genetic and environmental factors to ideological development using a role-play experiment investigating the development of opinions on a novel political issue. The results support the view that the process is bidirectional, suggesting that, like most traits, political ideology is produced by the complex interplay of genetic and (social/informational) environmental influences.

Stress Increases Peripheral Axon Growth and Regeneration through Glucocorticoid Receptor-Dependent Transcriptional Programs

PubMed Central

Alexander, Jessica K.; Madalena, Kathryn M.; Motti, Dario; Quach, Tam; Zha, Alicia; Webster Marketon, Jeanette

2017-01-01

Abstract Stress and glucocorticoid (GC) release are common behavioral and hormonal responses to injury or disease. In the brain, stress/GCs can alter neuron structure and function leading to cognitive impairment. Stress and GCs also exacerbate pain, but whether a corresponding change occurs in structural plasticity of sensory neurons is unknown. Here, we show that in female mice (Mus musculus) basal GC receptor (Nr3c1, also known as GR) expression in dorsal root ganglion (DRG) sensory neurons is 15-fold higher than in neurons in canonical stress-responsive brain regions (M. musculus). In response to stress or GCs, adult DRG neurite growth increases through mechanisms involving GR-dependent gene transcription. In vivo, prior exposure to an acute systemic stress increases peripheral nerve regeneration. These data have broad clinical implications and highlight the importance of stress and GCs as novel behavioral and circulating modifiers of neuronal plasticity. PMID:28828403

Brain, body, and cognition: Neural, physiological and self-report correlates of phobic and normative fear

PubMed Central

Schaefer, Hillary S.; Larson, Christine L.; Davidson, Richard J.; Coan, James A.

2014-01-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. PMID:24561099

Brain, body, and cognition: neural, physiological and self-report correlates of phobic and normative fear.

PubMed

Schaefer, Hillary S; Larson, Christine L; Davidson, Richard J; Coan, James A

2014-04-01

The phobic fear response appears to resemble an intense form of normal threat responding that can be induced in a nonthreatening situation. However, normative and phobic fear are rarely contrasted directly, thus the degree to which these two types of fear elicit similar neural and bodily responses is not well understood. To examine biological correlates of normal and phobic fear, 21 snake phobic and 21 nonphobic controls saw videos of slithering snakes, attacking snakes and fish in an event-related fMRI design. Simultaneous eletrodermal, pupillary, and self-reported affective responses were collected. Nonphobic fear activated a network of threat-responsive brain regions and involved pupillary dilation, electrodermal response and self-reported affect selective to the attacking snakes. Phobic fear recruited a large array of brain regions including those active in normal fear plus additional structures and also engendered increased pupil dilation, electrodermal and self-reported responses that were greater to any snake versus fish. Importantly, phobics showed greater between- and within-subject concordance among neural, electrodermal, pupillary, and subjective report measures. These results suggest phobic responses recruit overlapping but more strongly activated and more extensive networks of brain activity as compared to normative fear, and are characterized by greater concordance among neural activation, peripheral physiology and self-report. It is yet unclear whether concordance is unique to psychopathology, or rather simply an indicator of the intense fear seen in the phobic response, but these results underscore the importance of synchrony between brain, body, and cognition during the phobic reaction. Copyright © 2014. Published by Elsevier B.V.

Maintaining brain health by monitoring inflammatory processes: a mechanism to promote successful aging.

PubMed

Rosano, Caterina; Marsland, Anna L; Gianaros, Peter J

2012-02-01

Maintaining brain health promotes successful aging. The main determinants of brain health are the preservation of cognitive function and remaining free from structural and metabolic abnormalities, including loss of neuronal synapses, atrophy, small vessel disease and focal amyloid deposits visible by neuroimaging. Promising studies indicate that these determinants are to some extent modifiable, even among adults seventy years and older. Converging animal and human evidence further suggests that inflammation is a shared mechanism, contributing to both cognitive decline and abnormalities in brain structure and metabolism. Thus, inflammation may provide a target for intervention. Specifically, circulating inflammatory markers have been associated with declines in cognitive function and worsening of brain structural and metabolic characteristics. Additionally, it has been proposed that older brains are characterized by a sensitization to neuroinflammatory responses, even in the absence of overt disease. This increased propensity to central inflammation may contribute to poor brain health and premature brain aging. Still unknown is whether and how peripheral inflammatory factors directly contribute to decline of brain health. Human research is limited by the challenges of directly measuring neuroinflammation in vivo. This review assesses the role that inflammation may play in the brain changes that often accompany aging, focusing on relationships between peripheral inflammatory markers and brain health among well-functioning, community-dwelling adults seventy years and older. We propose that monitoring and maintaining lower levels of systemic and central inflammation among older adults could help preserve brain health and support successful aging. Hence, we also identify plausible ways and novel experimental study designs of maintaining brain health late in age through interventions that target the immune system.

Sleep Duration and Age-Related Changes in Brain Structure and Cognitive Performance

PubMed Central

Lo, June C.; Loh, Kep Kee; Zheng, Hui; Sim, Sam K.Y.; Chee, Michael W.L.

2014-01-01

Study Objectives: To investigate the contribution of sleep duration and quality to age-related changes in brain structure and cognitive performance in relatively healthy older adults. Design: Community-based longitudinal brain and cognitive aging study using a convenience sample. Setting: Participants were studied in a research laboratory. Participants: Relatively healthy adults aged 55 y and older at study commencement. Interventions: N/A. Measurements and Results: Participants underwent magnetic resonance imaging and neuropsychological assessment every 2 y. Subjective assessments of sleep duration and quality and blood samples were obtained. Each hour of reduced sleep duration at baseline augmented the annual expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after controlling for the effects of age, sex, education, and body mass index. In contrast, global sleep quality at baseline did not modulate either brain or cognitive aging. High-sensitivity C-reactive protein, a marker of systemic inflammation, showed no correlation with baseline sleep duration, brain structure, or cognitive performance. Conclusions: In healthy older adults, short sleep duration is associated with greater age-related brain atrophy and cognitive decline. These associations are not associated with elevated inflammatory responses among short sleepers. Citation: Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance. SLEEP 2014;37(7):1171-1178. PMID:25061245

Time Course of Brain Network Reconfiguration Supporting Inhibitory Control.

PubMed

Popov, Tzvetan; Westner, Britta U; Silton, Rebecca L; Sass, Sarah M; Spielberg, Jeffrey M; Rockstroh, Brigitte; Heller, Wendy; Miller, Gregory A

2018-05-02

Hemodynamic research has recently clarified key nodes and links in brain networks implementing inhibitory control. Although fMRI methods are optimized for identifying the structure of brain networks, the relatively slow temporal course of fMRI limits the ability to characterize network operation. The latter is crucial for developing a mechanistic understanding of how brain networks shift dynamically to support inhibitory control. To address this critical gap, we applied spectrally resolved Granger causality (GC) and random forest machine learning tools to human EEG data in two large samples of adults (test sample n = 96, replication sample n = 237, total N = 333, both sexes) who performed a color-word Stroop task. Time-frequency analysis confirmed that recruitment of inhibitory control accompanied by slower behavioral responses was related to changes in theta and alpha/beta power. GC analyses revealed directionally asymmetric exchanges within frontal and between frontal and parietal brain areas: top-down influence of superior frontal gyrus (SFG) over both dorsal ACC (dACC) and inferior frontal gyrus (IFG), dACC control over middle frontal gyrus (MFG), and frontal-parietal exchanges (IFG, precuneus, MFG). Predictive analytics confirmed a combination of behavioral and brain-derived variables as the best set of predictors of inhibitory control demands, with SFG theta bearing higher classification importance than dACC theta and posterior beta tracking the onset of behavioral response. The present results provide mechanistic insight into the biological implementation of a psychological phenomenon: inhibitory control is implemented by dynamic routing processes during which the target response is upregulated via theta-mediated effective connectivity within key PFC nodes and via beta-mediated motor preparation. SIGNIFICANCE STATEMENT Hemodynamic neuroimaging research has recently clarified regional structures in brain networks supporting inhibitory control. However, due to inherent methodological constraints, much of this research has been unable to characterize the temporal dynamics of such networks (e.g., direction of information flow between nodes). Guided by fMRI research identifying the structure of brain networks supporting inhibitory control, results of EEG source analysis in a test sample ( n = 96) and replication sample ( n = 237) using effective connectivity and predictive analytics strategies advance a model of inhibitory control by characterizing the precise temporal dynamics by which this network operates and exemplify an approach by which mechanistic models can be developed for other key psychological processes. Copyright © 2018 the authors 0270-6474/18/384348-09$15.00/0.

Bilirubin and its oxidation products damage brain white matter

PubMed Central

Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

2014-01-01

Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

Numerical study of the impact response of woodpecker's head

NASA Astrophysics Data System (ADS)

Zhu, Zhao Dan; Ma, Guo Jun; Wu, Cheng Wei; Chen, Zhen

2012-12-01

Woodpecker can beat trees 20-25 times per second and lasts for several seconds, with a 1200 g deceleration, but it appears that they never get brain concussion. How does the stress wave propagate from the beak tip to brain and how does a woodpecker protect itself from brain damage? In this paper, we establish a finite element model of typical woodpecker head based on its X-ray tomography images and conduct the numerical analysis of the impact response of the woodpecker's head by using a viscoelasticity material model. Especially, the woodpecker head response to an impact speed of 7 m/s is investigated to explore the stress concentration zone and how the stress wave propagates in its head. The numerical results show that the stress wave in the head propagates from the upper beak to back skull and is reduced by the specific structure of hyoid and viscoelasticity of biomaterials. The maximum stresses in skull and brain are both below the safe level. The stress in skull almost disappears before the next impact. The stress in brain lasts for a little longer but shows smaller value with little variation. The stress is impossible to accumulate in the limited pecking time, so the brain damage can be avoided.

Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

NASA Astrophysics Data System (ADS)

Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

2017-03-01

Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

Glucose, Lactate, and Shuttling of Metabolites in Vertebrate Retinas

PubMed Central

Hurley, James B.; Lindsay, Kenneth J.; Du, Jianhai

2016-01-01

The vertebrate retina has specific functions and structures that give it a unique set of constraints on the way in which it can produce and use metabolic energy. The retina’s response to illumination influences its energy requirements, and the retina’s laminated structure influences the extent to which neurons and glia can access metabolic fuels. There are fundamental differences between energy metabolism in retina and that in brain. The retina relies on aerobic glycolysis much more than the brain does, and morphological differences between retina and brain limit the types of metabolic relationships that are possible between neurons and glia. This Mini-Review summarizes the unique metabolic features of the retina with a focus on the role of lactate shuttling. PMID:25801286

Baby schema modulates the brain reward system in nulliparous women.

PubMed

Glocker, Melanie L; Langleben, Daniel D; Ruparel, Kosha; Loughead, James W; Valdez, Jeffrey N; Griffin, Mark D; Sachser, Norbert; Gur, Ruben C

2009-06-02

Ethologist Konrad Lorenz defined the baby schema ("Kindchenschema") as a set of infantile physical features, such as round face and big eyes, that is perceived as cute and motivates caretaking behavior in the human, with the evolutionary function of enhancing offspring survival. The neural basis of this fundamental altruistic instinct is not well understood. Prior studies reported a pattern of brain response to pictures of children, but did not dissociate the brain response to baby schema from the response to children. Using functional magnetic resonance imaging and controlled manipulation of the baby schema in infant faces, we found that baby schema activates the nucleus accumbens, a key structure of the mesocorticolimbic system mediating reward processing and appetitive motivation, in nulliparous women. Our findings suggest that engagement of the mesocorticolimbic system is the neurophysiologic mechanism by which baby schema promotes human caregiving, regardless of kinship.

Reversible Holmes' tremor due to spontaneous intracranial hypotension.

PubMed

Iyer, Rajesh Shankar; Wattamwar, Pandurang; Thomas, Bejoy

2017-07-27

Holmes' tremor is a low-frequency hand tremor and has varying amplitude at different phases of motion. It is usually unilateral and does not respond satisfactorily to drugs and thus considered irreversible. Structural lesions in the thalamus and brainstem or cerebellum are usually responsible for Holmes' tremor. We present a 23-year-old woman who presented with unilateral Holmes' tremor. She also had hypersomnolence and headache in the sitting posture. Her brain imaging showed brain sagging and deep brain swelling due to spontaneous intracranial hypotension (SIH). She was managed conservatively and had a total clinical and radiological recovery. The brain sagging with the consequent distortion of the midbrain and diencephalon was responsible for this clinical presentation. SIH may be considered as one of the reversible causes of Holmes' tremor. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mapping the "Depression Switch" During Intraoperative Testing of Subcallosal Cingulate Deep Brain Stimulation.

PubMed

Choi, Ki Sueng; Riva-Posse, Patricio; Gross, Robert E; Mayberg, Helen S

2015-11-01

The clinical utility of monitoring behavioral changes during intraoperative testing of subcallosal cingulate deep brain stimulation is unknown. To characterize the structural connectivity correlates of deep brain stimulation-evoked behavioral effects using probabilistic tractography in depression. Categorization of acute behavioral effects was conducted in 9 adults undergoing deep brain stimulation implantation surgery for chronic treatment-resistant depression in a randomized and blinded testing session at Emory University. Patients were studied from September 1, 2011, through June 30, 2013. Post hoc analyses of the structural tractography patterns mediating distinct categories of evoked behavioral effects were defined, including the best response overall. Data analyses were performed from May 1 through July 1, 2015. Categorization of stimulation-induced transient behavioral effects and delineation of the shared white matter tracts mediating response subtypes. Among the 9 patients, 72 active and 36 sham trials were recorded. The following stereotypical behavior patterns were identified: changes in interoceptive (noted changes in body state in 30 of 72 active and 4 of 36 sham trials) and in exteroceptive (shift in attention from patient to others in 9 of 72 active and 0 sham trials) awareness. The best response was a combination of exteroceptive and interoceptive changes at a single left contact for all 9 patients. Structural connectivity showed that the best response contacts had a pattern of connections to the bilateral ventromedial frontal cortex (via forceps minor and left uncinate fasciculus) and to the cingulate cortex (via left cingulum bundle), whereas behaviorally salient but nonbest contacts had only cingulate involvement. The involvement of the 3 white matter bundles during stimulation of the best contacts suggests a mechanism for the observed transient "depression switch." This analysis of transient behavior changes during intraoperative deep brain stimulation of the subcallosal cingulate and the subsequent identification of unique connectivity patterns may provide a biomarker of a rapid-onset depression switch to guide surgical implantation and to refine and optimize algorithms for the selection of contacts in long-term stimulation for treatment-resistant depression.

Individual Functional ROI Optimization via Maximization of Group-wise Consistency of Structural and Functional Profiles

PubMed Central

Li, Kaiming; Guo, Lei; Zhu, Dajiang; Hu, Xintao; Han, Junwei; Liu, Tianming

2013-01-01

Studying connectivities among functional brain regions and the functional dynamics on brain networks has drawn increasing interest. A fundamental issue that affects functional connectivity and dynamics studies is how to determine the best possible functional brain regions or ROIs (regions of interest) for a group of individuals, since the connectivity measurements are heavily dependent on ROI locations. Essentially, identification of accurate, reliable and consistent corresponding ROIs is challenging due to the unclear boundaries between brain regions, variability across individuals, and nonlinearity of the ROIs. In response to these challenges, this paper presents a novel methodology to computationally optimize ROIs locations derived from task-based fMRI data for individuals so that the optimized ROIs are more consistent, reproducible and predictable across brains. Our computational strategy is to formulate the individual ROI location optimization as a group variance minimization problem, in which group-wise consistencies in functional/structural connectivity patterns and anatomic profiles are defined as optimization constraints. Our experimental results from multimodal fMRI and DTI data show that the optimized ROIs have significantly improved consistency in structural and functional profiles across individuals. These improved functional ROIs with better consistency could contribute to further study of functional interaction and dynamics in the human brain. PMID:22281931

Rat strain differences in brain structure and neurochemistry in response to binge alcohol.

PubMed

Zahr, Natalie M; Mayer, Dirk; Rohlfing, Torsten; Hsu, Oliver; Vinco, Shara; Orduna, Juan; Luong, Richard; Bell, Richard L; Sullivan, Edith V; Pfefferbaum, Adolf

2014-01-01

Ventricular enlargement is a robust phenotype of the chronically dependent alcoholic human brain, yet the mechanism of ventriculomegaly is unestablished. Heterogeneous stock Wistar rats administered binge EtOH (3 g/kg intragastrically every 8 h for 4 days to average blood alcohol levels (BALs) of 250 mg/dL) demonstrate profound but reversible ventricular enlargement and changes in brain metabolites (e.g., N-acetylaspartate (NAA) and choline-containing compounds (Cho)). Here, alcohol-preferring (P) and alcohol-nonpreferring (NP) rats systematically bred from heterogeneous stock Wistar rats for differential alcohol drinking behavior were compared with Wistar rats to determine whether genetic divergence and consequent morphological and neurochemical variation affect the brain's response to binge EtOH treatment. The three rat lines were dosed equivalently and approached similar BALs. Magnetic resonance imaging and spectroscopy evaluated the effects of binge EtOH on brain. As observed in Wistar rats, P and NP rats showed decreases in NAA. Neither P nor NP rats, however, responded to EtOH intoxication with ventricular expansion or increases in Cho levels as previously noted in Wistar rats. Increases in ventricular volume correlated with increases in Cho in Wistar rats. The latter finding suggests that ventricular volume expansion is related to adaptive changes in brain cell membranes in response to binge EtOH. That P and NP rats responded differently to EtOH argues for intrinsic differences in their brain cell membrane composition. Further, differential metabolite responses to EtOH administration by rat strain implicate selective genetic variation as underlying heterogeneous effects of chronic alcoholism in the human condition.

Exploring avian deep-brain photoreceptors and their role in activating the neuroendocrine regulation of gonadal development.

PubMed

Kuenzel, Wayne J; Kang, Seong W; Zhou, Z Jimmy

2015-04-01

In the eyes of mammals, specialized photoreceptors called intrinsically photosensitive retinal ganglion cells (ipRGC) have been identified that sense photoperiodic or daylight exposure, providing them over time with seasonal information. Detectors of photoperiods are critical in vertebrates, particularly for timing the onset of reproduction each year. In birds, the eyes do not appear to monitor photoperiodic information; rather, neurons within at least 4 different brain structures have been proposed to function in this capacity. Specialized neurons, called deep brain photoreceptors (DBP), have been found in the septum and 3 hypothalamic areas. Within each of the 4 brain loci, one or more of 3 unique photopigments, including melanopsin, neuropsin, and vertebrate ancient opsin, have been identified. An experiment was designed to characterize electrophysiological responses of neurons proposed to be avian DBP following light stimulation. A second study used immature chicks raised under short-day photoperiods and transferred to long day lengths. Gene expression of photopigments was then determined in 3 septal-hypothalamic regions. Preliminary electrophysiological data obtained from patch-clamping neurons in brain slices have shown that bipolar neurons in the lateral septal organ responded to photostimulation comparable with mammalian ipRGC, particularly by showing depolarization and a delayed, slow response to directed light stimulation. Utilizing real-time reverse-transcription PCR, it was found that all 3 photopigments showed significantly increased gene expression in the septal-hypothalamic regions in chicks on the third day after being transferred to long-day photoperiods. Each dissected region contained structures previously proposed to have DBP. The highly significant increased gene expression for all 3 photopigments on the third, long-day photoperiod in brain regions proposed to contain 4 structures with DBP suggests that all 3 types of DBP (melanopsin, neuropsin, and vertebrate ancient opsin) in more than one neural site in the septal-hypothalamic area are involved in reproductive function. The neural response to light of at least 2 of the proposed DBP in the septal/hypothalamic region resembles the primitive, functional, sensory ipRGC well characterized in mammals. ©2015 Poultry Science Association Inc.

Processing of hierarchical syntactic structure in music.

PubMed

Koelsch, Stefan; Rohrmeier, Martin; Torrecuso, Renzo; Jentschke, Sebastian

2013-09-17

Hierarchical structure with nested nonlocal dependencies is a key feature of human language and can be identified theoretically in most pieces of tonal music. However, previous studies have argued against the perception of such structures in music. Here, we show processing of nonlocal dependencies in music. We presented chorales by J. S. Bach and modified versions in which the hierarchical structure was rendered irregular whereas the local structure was kept intact. Brain electric responses differed between regular and irregular hierarchical structures, in both musicians and nonmusicians. This finding indicates that, when listening to music, humans apply cognitive processes that are capable of dealing with long-distance dependencies resulting from hierarchically organized syntactic structures. Our results reveal that a brain mechanism fundamental for syntactic processing is engaged during the perception of music, indicating that processing of hierarchical structure with nested nonlocal dependencies is not just a key component of human language, but a multidomain capacity of human cognition.

Wavelet analysis of head acceleration response under dirac excitation for early oedema detection.

PubMed

Kostopoulos, V; Loutas, T H; Derdas, C; Douzinas, E

2008-04-01

The present work deals with the application of an innovative in-house developed wavelet-based methodology for the analysis of the acceleration responses of a human head complex model as a simulated diffused oedema progresses. The human head complex has been modeled as a structure consisting of three confocal prolate spheroids, whereas the three defined regions by the system of spheroids, from the outside to the inside, represent the scull, the region of cerebrospinal fluid, and the brain tissue. A Dirac-like pulse has been used to excite the human head complex model and the acceleration response of the system has been calculated and analyzed via the wavelet-based methodology. For the purpose of the present analysis, a wave propagation commercial finite element code, LS-DYNA 3D, has been used. The progressive diffused oedema was modeled via consecutive increases in brain volume accompanied by a decrease in brain density. It was shown that even a small increase in brain volume (at the level of 0.5%) can be identified by the effect it has on the vibration characteristics of the human head complex. More precisely, it was found that for some of the wavelet decomposition levels, the energy content changes monotonically as the brain volume increases, thus providing a useful index of monitoring an oncoming brain oedema before any brain damage appears due to uncontrolled intracranial hypertension. For the purpose of the present work and for the levels of brain volume increase considered in the present analysis, no pressure increase was assumed into the cranial vault and, associatively, no brain compliance variation.

Effects of Ethanol on Brain Extracellular Matrix: Implications for Alcohol Use Disorder

PubMed Central

Lasek, Amy W.

2016-01-01

The brain extracellular matrix (ECM) occupies the space between cells and is involved in cell-matrix and cell-cell adhesion. However, in addition to providing structural support to brain tissue, the ECM activates cell signaling and controls synaptic transmission. The expression and activity of brain ECM components are regulated by alcohol exposure. This review will discuss what is currently known about the effects of alcohol on the activity and expression of brain ECM components. An interpretation of how these changes might promote alcohol use disorder (AUD) will be also provided. Ethanol exposure decreases levels of structural proteins involved in the interstitial matrix and basement membrane, with a concomitant increase in proteolytic enzymes that degrade these components. In contrast, ethanol exposure generally increases perineuronal net (PN) components. Because the ECM has been shown to regulate both synaptic plasticity and behavioral responses to drugs of abuse, regulation of the brain ECM by alcohol may be relevant to the development of alcoholism. Although investigation of the function of brain ECM in alcohol abuse is still in early stages, a greater understanding of the interplay between ECM and alcohol might lead to novel therapeutic strategies for treating AUD. PMID:27581478

Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

PubMed Central

Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

2014-01-01

The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control. PMID:24416397

Reliability of a novel, semi-quantitative scale for classification of structural brain magnetic resonance imaging in children with cerebral palsy.

PubMed

Fiori, Simona; Cioni, Giovanni; Klingels, Katrjin; Ortibus, Els; Van Gestel, Leen; Rose, Stephen; Boyd, Roslyn N; Feys, Hilde; Guzzetta, Andrea

2014-09-01

To describe the development of a novel rating scale for classification of brain structural magnetic resonance imaging (MRI) in children with cerebral palsy (CP) and to assess its interrater and intrarater reliability. The scale consists of three sections. Section 1 contains descriptive information about the patient and MRI. Section 2 contains the graphical template of brain hemispheres onto which the lesion is transposed. Section 3 contains the scoring system for the quantitative analysis of the lesion characteristics, grouped into different global scores and subscores that assess separately side, regions, and depth. A larger interrater and intrarater reliability study was performed in 34 children with CP (22 males, 12 females; mean age at scan of 9 y 5 mo [SD 3 y 3 mo], range 4 y-16 y 11 mo; Gross Motor Function Classification System level I, [n=22], II [n=10], and level III [n=2]). Very high interrater and intrarater reliability of the total score was found with indices above 0.87. Reliability coefficients of the lobar and hemispheric subscores ranged between 0.53 and 0.95. Global scores for hemispheres, basal ganglia, brain stem, and corpus callosum showed reliability coefficients above 0.65. This study presents the first visual, semi-quantitative scale for classification of brain structural MRI in children with CP. The high degree of reliability of the scale supports its potential application for investigating the relationship between brain structure and function and examining treatment response according to brain lesion severity in children with CP. © 2014 Mac Keith Press.

In Vivo Investigation of the Effectiveness of a Hyper-viscoelastic Model in Simulating Brain Retraction

PubMed Central

Li, Ping; Wang, Weiwei; Zhang, Chenxi; An, Yong; Song, Zhijian

2016-01-01

Intraoperative brain retraction leads to a misalignment between the intraoperative positions of the brain structures and their previous positions, as determined from preoperative images. In vitro swine brain sample uniaxial tests showed that the mechanical response of brain tissue to compression and extension could be described by the hyper-viscoelasticity theory. The brain retraction caused by the mechanical process is a combination of brain tissue compression and extension. In this paper, we first constructed a hyper-viscoelastic framework based on the extended finite element method (XFEM) to simulate intraoperative brain retraction. To explore its effectiveness, we then applied this framework to an in vivo brain retraction simulation. The simulation strictly followed the clinical scenario, in which seven swine were subjected to brain retraction. Our experimental results showed that the hyper-viscoelastic XFEM framework is capable of simulating intraoperative brain retraction and improving the navigation accuracy of an image-guided neurosurgery system (IGNS). PMID:27387301

Data-driven analysis of functional brain interactions during free listening to music and speech.

PubMed

Fang, Jun; Hu, Xintao; Han, Junwei; Jiang, Xi; Zhu, Dajiang; Guo, Lei; Liu, Tianming

2015-06-01

Natural stimulus functional magnetic resonance imaging (N-fMRI) such as fMRI acquired when participants were watching video streams or listening to audio streams has been increasingly used to investigate functional mechanisms of the human brain in recent years. One of the fundamental challenges in functional brain mapping based on N-fMRI is to model the brain's functional responses to continuous, naturalistic and dynamic natural stimuli. To address this challenge, in this paper we present a data-driven approach to exploring functional interactions in the human brain during free listening to music and speech streams. Specifically, we model the brain responses using N-fMRI by measuring the functional interactions on large-scale brain networks with intrinsically established structural correspondence, and perform music and speech classification tasks to guide the systematic identification of consistent and discriminative functional interactions when multiple subjects were listening music and speech in multiple categories. The underlying premise is that the functional interactions derived from N-fMRI data of multiple subjects should exhibit both consistency and discriminability. Our experimental results show that a variety of brain systems including attention, memory, auditory/language, emotion, and action networks are among the most relevant brain systems involved in classic music, pop music and speech differentiation. Our study provides an alternative approach to investigating the human brain's mechanism in comprehension of complex natural music and speech.

Neurovascular abnormalities in brain disorders: highlights with angiogenesis and magnetic resonance imaging studies.

PubMed

Chen, Chiao-Chi V; Chen, Yu-Chen; Hsiao, Han-Yun; Chang, Chen; Chern, Yijuang

2013-07-05

The coupling between neuronal activity and vascular responses is controlled by the neurovascular unit (NVU), which comprises multiple cell types. Many different types of dysfunction in these cells may impair the proper control of vascular responses by the NVU. Magnetic resonance imaging, which is the most powerful tool available to investigate neurovascular structures or functions, will be discussed in the present article in relation to its applications and discoveries. Because aberrant angiogenesis and vascular remodeling have been increasingly reported as being implicated in brain pathogenesis, this review article will refer to this hallmark event when suitable.

Gene expression changes in female zebrafish (Danio rerio) brain in response to acute exposure to methylmercury

USGS Publications Warehouse

Richter, Catherine A.; Garcia-Reyero, Natàlia; Martyniuk, Chris; Knoebl, Iris; Pope, Marie; Wright-Osment, Maureen K.; Denslow, Nancy D.; Tillitt, Donald E.

2011-01-01

Methylmercury (MeHg) is a potent neurotoxicant and endocrine disruptor that accumulates in aquatic systems. Previous studies have shown suppression of hormone levels in both male and female fish, suggesting effects on gonadotropin regulation in the brain. The gene expression profile in adult female zebrafish whole brain induced by acute (96 h) MeHg exposure was investigated. Fish were exposed by injection to 0 or 0.5(mu or u)g MeHg/g. Gene expression changes in the brain were examined using a 22,000-feature zebrafish microarray. At a significance level of p

Diabetes dietary management alters responses to food pictures in brain regions associated with motivation and emotion: a functional magnetic resonance imaging study.

PubMed

Chechlacz, M; Rotshtein, P; Klamer, S; Porubská, K; Higgs, S; Booth, D; Fritsche, A; Preissl, H; Abele, H; Birbaumer, N; Nouwen, A

2009-03-01

We hypothesised that living with type 2 diabetes would enhance responses to pictures of foods in brain regions known to be involved in learnt food sensory motivation and that these stronger activations would relate to scores for dietary adherence in diabetes and to measures of potential difficulties in adherence. We compared brain responses to food images of 11 people with type 2 diabetes and 12 healthy control participants, matched for age and weight, using functional magnetic resonance imaging (fMRI). Having type 2 diabetes increased responses to pictured foods in the insula, orbitofrontal cortex (OFC) and basal ganglia and, within these regions, the effect of the fat content of the foods was larger in participants with type 2 diabetes than in healthy controls. Furthermore, increased activation to food within the insula and OFC positively correlated with external eating, dietary self-efficacy and dietary self-care. In contrast, responses within subcortical structures (amygdala and basal ganglia) were positively correlated with emotional eating and rated appetite for the food stimuli and negatively correlated with dietary self-care. Type 2 diabetes is associated with changes in brain responses to food that are modulated by dietary self-care. We propose that this is linked to the need to follow a life-long restrictive diet.

How does morality work in the brain? A functional and structural perspective of moral behavior

PubMed Central

Pascual, Leo; Rodrigues, Paulo; Gallardo-Pujol, David

2013-01-01

Neural underpinnings of morality are not yet well understood. Researchers in moral neuroscience have tried to find specific structures and processes that shed light on how morality works. Here, we review the main brain areas that have been associated with morality at both structural and functional levels and speculate about how it can be studied. Orbital and ventromedial prefrontal cortices are implicated in emotionally-driven moral decisions, while dorsolateral prefrontal cortex appears to moderate its response. These competing processes may be mediated by the anterior cingulate cortex. Parietal and temporal structures play important roles in the attribution of others' beliefs and intentions. The insular cortex is engaged during empathic processes. Other regions seem to play a more complementary role in morality. Morality is supported not by a single brain circuitry or structure, but by several circuits overlapping with other complex processes. The identification of the core features of morality and moral-related processes is needed. Neuroscience can provide meaningful insights in order to delineate the boundaries of morality in conjunction with moral psychology. PMID:24062650

Personality changes following brain injury as a grief response to the loss of sense of self: phenomenological themes as indices of local lability and neurocognitive structuring as psychotherapy.

PubMed

Persinger, M A

1993-06-01

Both theoretical and empirical observations suggest that significant alterations in self-concept should occur following most closed head injuries because of diffuse synaptic modification within the temporofrontal regions; this loss of the sense of self should evoke a grief-like response sequence and should encourage paranormal/religious experiences during the subsequent months to years. The marked consistency between phenomenological experiences and the results of neuropsychological assessments of 56 adults who had sustained brain injuries supported this hypothesis. Subsequent reports by these patients indicated that clinical translation of posttraumatic experiences into rational neurobehavioral terms and interventions tailored for the individual's specific pattern of brain "dysfunction" may facilitate adaptation during the grieving period.

Assessing the marks of change: how psychotherapy alters the brain structure in women with borderline personality disorder.

PubMed

Mancke, Falk; Schmitt, Ruth; Winter, Dorina; Niedtfeld, Inga; Herpertz, Sabine C; Schmahl, Christian

2017-12-13

There is increasing evidence that psychotherapy can alter the function of the brain of patients with borderline personality disorder (BPD). However, it is not known whether psychotherapy can also modify the brain structure of patients with BPD. We used structural MRI data of female patients with BPD before and after participation in 12 weeks of residential dialectical behavioural therapy (DBT) and compared them to data from female patients with BPD who received treatment as usual (TAU). We applied voxel-based morphometry to study voxel-wise changes in grey matter volume over time. We included 31 patients in the DBT group and 17 in the TAU group. Patients receiving DBT showed an increase of grey matter volume in the anterior cingulate cortex, inferior frontal gyrus and superior temporal gyrus together with an alteration of grey matter volume in the angular gyrus and supramarginal gyrus compared with patients receiving TAU. Furthermore, therapy response correlated with increase of grey matter volume in the angular gyrus. Only women were investigated, and groups differed in size, medication (controlled for) and intensity of the treatment condition. We found that DBT increased grey matter volume of brain regions that are critically implicated in emotion regulation and higher-order functions, such as mentalizing. The role of the angular gyrus for treatment response may reside in its cross-modal integrative function. These findings enhance our understanding of psychotherapy mechanisms of change and may foster the development of neurobiologically informed therapeutic interventions.

Brain magnetic resonance imaging findings and auditory brainstem response in a child with spastic paraplegia 2 due to a PLP1 splice site mutation.

PubMed

Kubota, Kazuo; Saito, Yoshiaki; Ohba, Chihiro; Saitsu, Hirotomo; Fukuyama, Tetsuhiro; Ishiyama, Akihiko; Saito, Takashi; Komaki, Hirofumi; Nakagawa, Eiji; Sugai, Kenji; Sasaki, Masayuki; Matsumoto, Naomichi

2015-01-01

A boy with spastic paraplegia type 2 (SPG2) due to a novel splice site mutation of PLP1 presented with progressive spasticity of lower limbs, which was first observed during late infancy, when he gained the ability to walk with support. His speech was slow and he had dysarthria. The patient showed mildly delayed intellectual development. Subtotal dysmyelination in the central nervous system was revealed, which was especially prominent in structures known to be myelinated during earlier period, whereas structures that are myelinated later were better myelinated. These findings on the brain magnetic resonance imaging were unusual for subjects with PLP1 mutations. Peaks I and II of the auditory brainstem response (ABR) were normally provoked, but peaks III-V were not clearly demarcated, similarly to the findings in Pelizaeus-Merzbacher disease. These findings of brain MRI and ABR may be characteristic for a subtype of SPG2 patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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

PubMed Central

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

2015-01-01

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

[Peculiarities of cerebral structures functioning in adolescents with achondroplasia].

PubMed

Skripnikov, A A; Dolganova, T I; Aranovich, A M

2013-01-01

Complex neurophysiological examination (rheoencephalography, electroencephalography) was carried out in 12 adolescents 12 to 18 years old in order to reveal the peculiarities of cerebral structures functioning in adolescents with achondroplasia. Some deviations from the normal values were found out: reduced blood filling of the brain vessels in the pools of a. carotis interna and a. vertebralis, rheoencephalographic signs of intracranial hypertension of mild degree and brain cycling characterized by moderate and significant amplitude increase, presence of pathological types (delta-, theta-) of the rhythmics and the reduction of the physiological ones (alpha-, beta-). At the same time the peculiarities of rheoencephalographic indices were observed while functional testings (hypercapnia, hyperoxia). Brain cycling differed from normal values by weaker response to the weight-bearing, mainly in alpha- and beta-ranges.

A viscoelastic analysis of the P56 mouse brain under large-deformation dynamic indentation.

PubMed

MacManus, David B; Pierrat, Baptiste; Murphy, Jeremiah G; Gilchrist, Michael D

2017-01-15

The brain is a complex organ made up of many different functional and structural regions consisting of different types of cells such as neurons and glia, as well as complex anatomical geometries. It is hypothesized that the different regions of the brain exhibit significantly different mechanical properties which may be attributed to the diversity of cells within individual brain regions. The regional viscoelastic properties of P56 mouse brain tissue, up to 70μm displacement, are presented and discussed in the context of traumatic brain injury, particularly how the different regions of the brain respond to mechanical loads. Force-relaxation data obtained from micro-indentation measurements were fit to both linear and quasi-linear viscoelastic models to determine the time and frequency domain viscoelastic response of the pons, cortex, medulla oblongata, cerebellum, and thalamus. The damping ratio of each region was also determined. Each region was found to have a unique mechanical response to the applied displacement, with the pons and thalamus exhibiting the largest and smallest force-response, respectively. All brain regions appear to have an optimal frequency for the dissipation of energies which lies between 1 and 10Hz. We present the first mechanical characterization of the viscoelastic response for different regions of mouse brain. Force-relaxation tests are performed under large strain dynamic micro-indentation, and viscoelastic models are used subsequently, providing time-dependent mechanical properties of brain tissue under loading conditions comparable to what is experienced in TBI. The unique mechanical properties of different brain regions are highlighted, with substantial variations in the viscoelastic properties and damping ratio of each region. Cortex and pons were the stiffest regions, while the thalamus and medulla were most compliant. The cerebellum and thalamus had highest damping ratio values and those of the medulla were lowest. The reported material parameters can be implemented into finite element computer models of the mouse to investigate the effects of trauma on individual brain regions. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Community structure in networks of functional connectivity: resolving functional organization in the rat brain with pharmacological MRI.

PubMed

Schwarz, Adam J; Gozzi, Alessandro; Bifone, Angelo

2009-08-01

In the study of functional connectivity, fMRI data can be represented mathematically as a network of nodes and links, where image voxels represent the nodes and the connections between them reflect a degree of correlation or similarity in their response. Here we show that, within this framework, functional imaging data can be partitioned into 'communities' of tightly interconnected voxels corresponding to maximum modularity within the overall network. We evaluated this approach systematically in application to networks constructed from pharmacological MRI (phMRI) of the rat brain in response to acute challenge with three different compounds with distinct mechanisms of action (d-amphetamine, fluoxetine, and nicotine) as well as vehicle (physiological saline). This approach resulted in bilaterally symmetric sub-networks corresponding to meaningful anatomical and functional connectivity pathways consistent with the purported mechanism of action of each drug. Interestingly, common features across all three networks revealed two groups of tightly coupled brain structures that responded as functional units independent of the specific neurotransmitter systems stimulated by the drug challenge, including a network involving the prefrontal cortex and sub-cortical regions extending from the striatum to the amygdala. This finding suggests that each of these networks includes general underlying features of the functional organization of the rat brain.

Left-right asymmetry is required for the habenulae to respond to both visual and olfactory stimuli.

PubMed

Dreosti, Elena; Vendrell Llopis, Nuria; Carl, Matthias; Yaksi, Emre; Wilson, Stephen W

2014-02-17

Left-right asymmetries are most likely a universal feature of bilaterian nervous systems and may serve to increase neural capacity by specializing equivalent structures on left and right sides for distinct roles. However, little is known about how asymmetries are encoded within vertebrate neural circuits and how lateralization influences processing of information in the brain. Consequently, it remains unclear the extent to which lateralization of the nervous system is important for normal cognitive and other brain functions and whether defects in lateralization contribute to neurological deficits. Here we show that sensory responses to light and odor are lateralized in larval zebrafish habenulae and that loss of brain asymmetry leads to concomitant loss of responsiveness to either visual or olfactory stimuli. We find that in wild-type zebrafish, most habenular neurons responding to light are present on the left, whereas neurons responding to odor are more frequent on the right. Manipulations that reverse the direction of brain asymmetry reverse the functional properties of habenular neurons, whereas manipulations that generate either double-left- or double-right-sided brains lead to loss of habenular responsiveness to either odor or light, respectively. Our results indicate that loss of brain lateralization has significant consequences upon sensory processing and circuit function. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Review. Neurobiological mechanisms for opponent motivational processes in addiction.

PubMed

Koob, George F; Le Moal, Michel

2008-10-12

The conceptualization of drug addiction as a compulsive disorder with excessive drug intake and loss of control over intake requires motivational mechanisms. Opponent process as a motivational theory for the negative reinforcement of drug dependence has long required a neurobiological explanation. Key neurochemical elements involved in reward and stress within basal forebrain structures involving the ventral striatum and extended amygdala are hypothesized to be dysregulated in addiction to convey the opponent motivational processes that drive dependence. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission such as dopamine and opioid peptides in the ventral striatum, but also recruitment of brain stress systems such as corticotropin-releasing factor (CRF), noradrenaline and dynorphin in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, anxiety-like responses and extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence and to contribute to stress-induced relapse. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for the long hypothesized opponent motivational processes responsible for the negative reinforcement driving addiction.

Object memory effects on figure assignment: conscious object recognition is not necessary or sufficient.

PubMed

Peterson, M A; de Gelder, B; Rapcsak, S Z; Gerhardstein, P C; Bachoud-Lévi, A

2000-01-01

In three experiments we investigated whether conscious object recognition is necessary or sufficient for effects of object memories on figure assignment. In experiment 1, we examined a brain-damaged participant, AD, whose conscious object recognition is severely impaired. AD's responses about figure assignment do reveal effects from memories of object structure, indicating that conscious object recognition is not necessary for these effects, and identifying the figure-ground test employed here as a new implicit test of access to memories of object structure. In experiments 2 and 3, we tested a second brain-damaged participant, WG, for whom conscious object recognition was relatively spared. Nevertheless, effects from memories of object structure on figure assignment were not evident in WG's responses about figure assignment in experiment 2, indicating that conscious object recognition is not sufficient for effects of object memories on figure assignment. WG's performance sheds light on AD's performance, and has implications for the theoretical understanding of object memory effects on figure assignment.

The Arnold-Chiari Malformation and Its Implications for Individuals with Spina Bifida and Hydrocephalus.

ERIC Educational Resources Information Center

Mittler, Joel E.

1986-01-01

The Arnold-Chiari malformation is present in most infants born with myelomeningocele (a form of spina bifida) and hydrocephalus. The syndrome is responsible for structural abnormalities in the brain, and peripheral nervous system. Etiology, symptoms, impact on central nervous system structures, surgical treatment, and implications for education…

Brain responses to sexual images in 46,XY women with complete androgen insensitivity syndrome are female-typical.

PubMed

Hamann, Stephan; Stevens, Jennifer; Vick, Janice Hassett; Bryk, Kristina; Quigley, Charmian A; Berenbaum, Sheri A; Wallen, Kim

2014-11-01

Androgens, estrogens, and sex chromosomes are the major influences guiding sex differences in brain development, yet their relative roles and importance remain unclear. Individuals with complete androgen insensitivity syndrome (CAIS) offer a unique opportunity to address these issues. Although women with CAIS have a Y chromosome, testes, and produce male-typical levels of androgens, they lack functional androgen receptors preventing responding to their androgens. Thus, they develop a female physical phenotype, are reared as girls, and develop into women. Because sexually differentiated brain development in primates is determined primarily by androgens, but may be affected by sex chromosome complement, it is currently unknown whether brain structure and function in women with CAIS is more like that of women or men. In the first functional neuroimaging study of (46,XY) women with CAIS, typical (46,XX) women, and typical (46, XY) men, we found that men showed greater amygdala activation to sexual images than did either typical women or women with CAIS. Typical women and women with CAIS had highly similar patterns of brain activation, indicating that a Y chromosome is insufficient for male-typical human brain responses. Because women with CAIS produce male-typical or elevated levels of testosterone which is aromatized to estradiol these results rule out aromatization of testosterone to estradiol as a determinate of sex differences in patterns of brain activation to sexual images. We cannot, however, rule out an effect of social experience on the brain responses of women with CAIS as all were raised as girls. Copyright © 2014 Elsevier Inc. All rights reserved.

Endocrine modulation of the adolescent brain: a review.

PubMed

Vigil, Pilar; Orellana, Renán F; Cortés, Manuel E; Molina, Carmen T; Switzer, Barbara E; Klaus, Hanna

2011-12-01

Neurophysiological and behavioral development is particularly complex in adolescence. Youngsters experience strong emotions and impulsivity, reduced self-control, and preference for actions which offer immediate rewards, among other behavioral patterns. Given the growing interest in endocrine effects on adolescent central nervous system development and their implications on later stages of life, this article reviews the effects of gonadal steroid hormones on the adolescent brain. These effects are classified as organizational, the capacity of steroids to determine nervous system structure during development, and activational, the ability of steroids to modify nervous activity to promote certain behaviors. During transition from puberty to adolescence, steroid hormones trigger various organizational phenomena related to structural brain circuit remodelling, determining adult behavioral response to steroids or sensory stimuli. These changes account for most male-female sexual dimorphism. In this stage sex steroids are involved in the main functional mechanisms responsible for organizational changes, namely myelination, neural pruning, apoptosis, and dendritic spine remodelling, activated only during embryonic development and during the transition from puberty to adolescence. This stage becomes a critical organizational window when the appropriately and timely exerted functions of steroid hormones and their interaction with some neurotransmitters on adolescent brain development are fundamental. Thus, understanding the phenomena linking steroid hormones and adolescent brain organization is crucial in the study of teenage behavior and in later assessment and treatment of anxiety, mood disorders, and depression. Adolescent behavior clearly evidences a stage of brain development influenced for the most part by steroid hormones. Copyright © 2011 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Migraine Subclassification via a Data-Driven Automated Approach Using Multimodality Factor Mixture Modeling of Brain Structure Measurements.

PubMed

Schwedt, Todd J; Si, Bing; Li, Jing; Wu, Teresa; Chong, Catherine D

2017-07-01

The current subclassification of migraine is according to headache frequency and aura status. The variability in migraine symptoms, disease course, and response to treatment suggest the presence of additional heterogeneity or subclasses within migraine. The study objective was to subclassify migraine via a data-driven approach, identifying latent factors by jointly exploiting multiple sets of brain structural features obtained via magnetic resonance imaging (MRI). Migraineurs (n = 66) and healthy controls (n = 54) had brain MRI measurements of cortical thickness, cortical surface area, and volumes for 68 regions. A multimodality factor mixture model was used to subclassify MRIs and to determine the brain structural factors that most contributed to the subclassification. Clinical characteristics of subjects in each subgroup were compared. Automated MRI classification divided the subjects into two subgroups. Migraineurs in subgroup #1 had more severe allodynia symptoms during migraines (6.1 ± 5.3 vs. 3.6 ± 3.2, P = .03), more years with migraine (19.2 ± 11.3 years vs 13 ± 8.3 years, P = .01), and higher Migraine Disability Assessment (MIDAS) scores (25 ± 22.9 vs 15.7 ± 12.2, P = .04). There were not differences in headache frequency or migraine aura status between the two subgroups. Data-driven subclassification of brain MRIs based upon structural measurements identified two subgroups. Amongst migraineurs, the subgroups differed in allodynia symptom severity, years with migraine, and migraine-related disability. Since allodynia is associated with this imaging-based subclassification of migraine and prior publications suggest that allodynia impacts migraine treatment response and disease prognosis, future migraine diagnostic criteria could consider allodynia when defining migraine subgroups. © 2017 American Headache Society.

Orbitrap mass spectrometry characterization of hybrid chondroitin/dermatan sulfate hexasaccharide domains expressed in brain.

PubMed

Robu, Adrian C; Popescu, Laurentiu; Munteanu, Cristian V A; Seidler, Daniela G; Zamfir, Alina D

2015-09-15

In the central nervous system, chondroitin/dermatan sulfate (CS/DS) glycosaminoglycans (GAGs) modulate neurotrophic effects and glial cell maturation during brain development. Previous reports revealed that GAG composition could be responsible for CS/DS activities in brain. In this work, for the structural characterization of DS- and CS-rich domains in hybrid GAG chains extracted from neural tissue, we have developed an advanced approach based on high-resolution mass spectrometry (MS) using nanoelectrospray ionization Orbitrap in the negative ion mode. Our high-resolution MS and multistage MS approach was developed and applied to hexasaccharides obtained from 4- and 14-week-old mouse brains by GAG digestion with chondroitin B and in parallel with AC I lyase. The expression of DS- and CS-rich domains in the two tissues was assessed comparatively. The analyses indicated an age-related structural variability of the CS/DS motifs. The older brain was found to contain more structures and a higher sulfation of DS-rich regions, whereas the younger brain was found to be characterized by a higher sulfation of CS-rich regions. By multistage MS using collision-induced dissociation, we also demonstrated the incidence in mouse brain of an atypical [4,5-Δ-GlcAGalNAc(IdoAGalNAc)2], presenting a bisulfated CS disaccharide formed by 3-O-sulfate-4,5-Δ-GlcA and 6-O-sulfate-GalNAc moieties. Copyright © 2015 Elsevier Inc. All rights reserved.

Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention.

PubMed

Szulc-Lerch, Kamila U; Timmons, Brian W; Bouffet, Eric; Laughlin, Suzanne; de Medeiros, Cynthia B; Skocic, Jovanka; Lerch, Jason P; Mabbott, Donald J

2018-01-01

There is growing evidence that exercise induced experience dependent plasticity may foster structural and functional recovery following brain injury. We examined the efficacy of exercise training for neural and cognitive recovery in long-term pediatric brain tumor survivors treated with radiation. We conducted a controlled clinical trial with crossover of exercise training (vs. no training) in a volunteer sample of 28 children treated with cranial radiation for brain tumors (mean age = 11.5 yrs.; mean time since diagnosis = 5.7 yrs). The endpoints were anatomical T1 MRI data and multiple behavioral outcomes presenting a broader analysis of structural MRI data across the entire brain. This included an analysis of changes in cortical thickness and brain volume using automated, user unbiased approaches. A series of general linear mixed effects models evaluating the effects of exercise training on cortical thickness were performed in a voxel and vertex-wise manner, as well as for specific regions of interest. In exploratory analyses, we evaluated the relationship between changes in cortical thickness after exercise with multiple behavioral outcomes, as well as the relation of these measures at baseline. Exercise was associated with increases in cortical thickness within the right pre and postcentral gyri. Other notable areas of increased thickness related to training were present in the left pre and postcentral gyri, left temporal pole, left superior temporal gyrus, and left parahippocampal gyrus. Further, we observed that compared to a separate cohort of healthy children, participants displayed multiple areas with a significantly thinner cortex prior to training and fewer differences following training, indicating amelioration of anatomical deficits. Partial least squares analysis (PLS) revealed specific patterns of relations between cortical thickness and various behavioral outcomes both after training and at baseline. Overall, our results indicate that exercise training in pediatric brain tumor patients treated with radiation has a beneficial impact on brain structure. We argue that exercise training should be incorporated into the development of neuro-rehabilitative treatments for long-term pediatric brain tumor survivors and other populations with acquired brain injury. (ClinicalTrials.gov, NCT01944761).

Culture Modulates the Brain Response to Harmonic Violations: An EEG Study on Hierarchical Syntactic Structure in Music.

PubMed

Akrami, Haleh; Moghimi, Sahar

2017-01-01

We investigated the role of culture in processing hierarchical syntactic structures in music. We examined whether violation of non-local dependencies manifest in event related potentials (ERP) for Western and Iranian excerpts by recording EEG while participants passively listened to sequences of modified/original excerpts. We also investigated oscillatory and synchronization properties of brain responses during processing of hierarchical structures. For the Western excerpt, subjective ratings of conclusiveness were marginally significant and the difference in the ERP components fell short of significance. However, ERP and behavioral results showed that while listening to culturally familiar music, subjects comprehended whether or not the hierarchical syntactic structure was fulfilled. Irregularities in the hierarchical structures of the Iranian excerpt elicited an early negativity in the central regions bilaterally, followed by two later negativities from 450-700 to 750-950 ms. The latter manifested throughout the scalp. Moreover, violations of hierarchical structure in the Iranian excerpt were associated with (i) an early decrease in the long range alpha phase synchronization, (ii) an early increase in the oscillatory activity in the beta band over the central areas, and (iii) a late decrease in the theta band phase synchrony between left anterior and right posterior regions. Results suggest that rhythmic structures and melodic fragments, representative of Iranian music, created a familiar context in which recognition of complex non-local syntactic structures was feasible for Iranian listeners. Processing of neural responses to the Iranian excerpt indicated neural mechanisms for processing of hierarchical syntactic structures in music at different levels of cortical integration.

ROS and brain diseases: the good, the bad, and the ugly.

PubMed

Popa-Wagner, Aurel; Mitran, Smaranda; Sivanesan, Senthilkumar; Chang, Edwin; Buga, Ana-Maria

2013-01-01

The brain is a major metabolizer of oxygen and yet has relatively feeble protective antioxidant mechanisms. This paper reviews the Janus-faced properties of reactive oxygen species. It will describe the positive aspects of moderately induced ROS but it will also outline recent research findings concerning the impact of oxidative and nitrooxidative stress on neuronal structure and function in neuropsychiatric diseases, including major depression. A common denominator of all neuropsychiatric diseases including schizophrenia and ADHD is an increased inflammatory response of the brain caused either by an exposure to proinflammatory agents during development or an accumulation of degenerated neurons, oxidized proteins, glycated products, or lipid peroxidation in the adult brain. Therefore, modulation of the prooxidant-antioxidant balance provides a therapeutic option which can be used to improve neuroprotection in response to oxidative stress. We also discuss the neuroprotective role of the nuclear factor erythroid 2-related factor (Nrf2) in the aged brain in response to oxidative stressors and nanoparticle-mediated delivery of ROS-scavenging drugs. The antioxidant therapy is a novel therapeutic strategy. However, the available drugs have pleiotropic actions and are not fully characterized in the clinic. Additional clinical trials are needed to assess the risks and benefits of antioxidant therapies for neuropsychiatric disorders.

An Epigenetic Gateway to Brain Tumor Cell Identity

PubMed Central

Mack, Stephen C.; Hubert, Christopher G.; Miller, Tyler E.; Taylor, Michael D.; Rich, Jeremy N.

2017-01-01

Precise targeting of genetic lesions alone has been insufficient to extend brain tumor patient survival. Brain cancer cells are diverse in their genetic, metabolic, and microenvironmental compositions, accounting for their phenotypic heterogeneity and disparate responses to therapy. These factors converge at the level of the epigenome, representing a unified node that can be disrupted by pharmacologic inhibition. Aberrant epigenomes define many childhood and adult brain cancers, as demonstrated by widespread changes to DNA methylation patterns, redistribution of histone marks, and disruption of chromatin structure. In this review, we describe the convergence of genetic, metabolic, and micro-environmental factors upon mechanisms of epigenetic deregulation in brain cancer. We discuss how aberrant epigenetic pathways identified in brain tumors affect cell identity, cell state, and neoplastic transformation, in addition to the potential to exploit these alterations as novel therapeutic strategies for the treatment of brain cancer. PMID:26713744

Functional MRI Preprocessing in Lesioned Brains: Manual Versus Automated Region of Interest Analysis

PubMed Central

Garrison, Kathleen A.; Rogalsky, Corianne; Sheng, Tong; Liu, Brent; Damasio, Hanna; Winstein, Carolee J.; Aziz-Zadeh, Lisa S.

2015-01-01

Functional magnetic resonance imaging (fMRI) has significant potential in the study and treatment of neurological disorders and stroke. Region of interest (ROI) analysis in such studies allows for testing of strong a priori clinical hypotheses with improved statistical power. A commonly used automated approach to ROI analysis is to spatially normalize each participant’s structural brain image to a template brain image and define ROIs using an atlas. However, in studies of individuals with structural brain lesions, such as stroke, the gold standard approach may be to manually hand-draw ROIs on each participant’s non-normalized structural brain image. Automated approaches to ROI analysis are faster and more standardized, yet are susceptible to preprocessing error (e.g., normalization error) that can be greater in lesioned brains. The manual approach to ROI analysis has high demand for time and expertise, but may provide a more accurate estimate of brain response. In this study, commonly used automated and manual approaches to ROI analysis were directly compared by reanalyzing data from a previously published hypothesis-driven cognitive fMRI study, involving individuals with stroke. The ROI evaluated is the pars opercularis of the inferior frontal gyrus. Significant differences were identified in task-related effect size and percent-activated voxels in this ROI between the automated and manual approaches to ROI analysis. Task interactions, however, were consistent across ROI analysis approaches. These findings support the use of automated approaches to ROI analysis in studies of lesioned brains, provided they employ a task interaction design. PMID:26441816

Preliminary evidence for obesity and elevations in fasting insulin mediating associations between cortisol awakening response and hippocampal volumes and frontal atrophy.

PubMed

Ursache, Alexandra; Wedin, William; Tirsi, Aziz; Convit, Antonio

2012-08-01

Recent studies have demonstrated alterations in the cortisol awakening response (CAR) and brain abnormalities in adults with obesity and type 2 diabetes mellitus (T2DM). While adolescents with T2DM exhibit similar brain abnormalities, less is known about whether brain impairments and hypothalamic-pituitary-adrenal (HPA) axis abnormalities are already present in adolescents with pre-diabetic conditions such as insulin resistance (IR). This study included 33 adolescents with IR and 20 without IR. Adolescents with IR had a blunted CAR, smaller hippocampal volumes, and greater frontal lobe atrophy compared to controls. Mediation analyses indicated pathways whereby a smaller CAR was associated with higher BMI which was in turn associated with fasting insulin levels, which in turn was related to smaller hippocampal volume and greater frontal lobe atrophy. While we had hypothesized that HPA dysregulation may result from brain abnormalities, our findings suggest that HPA dysregulation may also impact brain structures through associations with metabolic abnormalities. Copyright © 2012 Elsevier Ltd. All rights reserved.

Low-Frequency Cortical Oscillations Entrain to Subthreshold Rhythmic Auditory Stimuli

PubMed Central

Schroeder, Charles E.; Poeppel, David; van Atteveldt, Nienke

2017-01-01

Many environmental stimuli contain temporal regularities, a feature that can help predict forthcoming input. Phase locking (entrainment) of ongoing low-frequency neuronal oscillations to rhythmic stimuli is proposed as a potential mechanism for enhancing neuronal responses and perceptual sensitivity, by aligning high-excitability phases to events within a stimulus stream. Previous experiments show that rhythmic structure has a behavioral benefit even when the rhythm itself is below perceptual detection thresholds (ten Oever et al., 2014). It is not known whether this “inaudible” rhythmic sound stream also induces entrainment. Here we tested this hypothesis using magnetoencephalography and electrocorticography in humans to record changes in neuronal activity as subthreshold rhythmic stimuli gradually became audible. We found that significant phase locking to the rhythmic sounds preceded participants' detection of them. Moreover, no significant auditory-evoked responses accompanied this prethreshold entrainment. These auditory-evoked responses, distinguished by robust, broad-band increases in intertrial coherence, only appeared after sounds were reported as audible. Taken together with the reduced perceptual thresholds observed for rhythmic sequences, these findings support the proposition that entrainment of low-frequency oscillations serves a mechanistic role in enhancing perceptual sensitivity for temporally predictive sounds. This framework has broad implications for understanding the neural mechanisms involved in generating temporal predictions and their relevance for perception, attention, and awareness. SIGNIFICANCE STATEMENT The environment is full of rhythmically structured signals that the nervous system can exploit for information processing. Thus, it is important to understand how the brain processes such temporally structured, regular features of external stimuli. Here we report the alignment of slowly fluctuating oscillatory brain activity to external rhythmic structure before its behavioral detection. These results indicate that phase alignment is a general mechanism of the brain to process rhythmic structure and can occur without the perceptual detection of this temporal structure. PMID:28411273

Brain structural connectivity and context-dependent extinction memory.

PubMed

Hermann, Andrea; Stark, Rudolf; Blecker, Carlo R; Milad, Mohammed R; Merz, Christian J

2017-08-01

Extinction of conditioned fear represents an important mechanism in the treatment of anxiety disorders. Return of fear after successful extinction or exposure therapy in patients with anxiety disorders might be linked to poor temporal or contextual generalization of extinction due to individual differences in brain structural connectivity. The goal of this magnetic resonance imaging study was therefore to investigate the association of context-dependent extinction recall with brain structural connectivity. Diffusion-tensor imaging was used to determine the fractional anisotropy as a measure of white matter structural integrity of fiber tracts connecting central brain regions of the fear and extinction circuit (uncinate fasciculus, cingulum). Forty-five healthy men participated in a two-day fear conditioning experiment with fear acquisition in context A and extinction learning in context B on the first day. Extinction recall in the extinction context as well as renewal in the acquisition context and a novel context C took place one day later. Renewal of conditioned fear (skin conductance responses) in the acquisition context was associated with higher structural integrity of the hippocampal part of the cingulum. Enhanced structural integrity of the cingulum might be related to stronger hippocampal modulation of the dorsal anterior cingulate cortex, a region important for modulating conditioned fear output by excitatory projections to the amygdala. This finding underpins the crucial role of individual differences in the structural integrity of relevant fiber tracts for context-dependent extinction recall and return of fear after exposure therapy in anxiety disorders. © 2017 Wiley Periodicals, Inc.

Severe Urban Outdoor Air Pollution and Children's Structural and Functional Brain Development, From Evidence to Precautionary Strategic Action.

PubMed

D'Angiulli, Amedeo

2018-01-01

According to the latest estimates, about 2 billion children around the world are exposed to severe urban outdoor air pollution. Transdisciplinary, multi-method findings from epidemiology, developmental neuroscience, psychology, and pediatrics, show detrimental outcomes associated with pre- and postnatal exposure are found at all ages. Affected brain-related functions include perceptual and sensory information processing, intellectual and cognitive development, memory and executive functions, emotion and self-regulation, and academic achievement. Correspondingly, with the breakdown of natural barriers against entry and translocation of toxic particles in the brain, the most common structural changes are responses promoting neuroinflammation and indicating early neurodegenerative processes. In spite of the gaps in current scientific knowledge and the challenges posed by non-scientific issues that influence policy, the evidence invites the conclusion that urban outdoor air pollution is a serious threat to healthy brain development which may set the conditions for neurodegenerative diseases. Such evidence supports the perspective that urgent strategic precautionary actions, minimizing exposure and attenuating its effects, are needed to protect children and their brain development.

Severe Urban Outdoor Air Pollution and Children’s Structural and Functional Brain Development, From Evidence to Precautionary Strategic Action

PubMed Central

D’Angiulli, Amedeo

2018-01-01

According to the latest estimates, about 2 billion children around the world are exposed to severe urban outdoor air pollution. Transdisciplinary, multi-method findings from epidemiology, developmental neuroscience, psychology, and pediatrics, show detrimental outcomes associated with pre- and postnatal exposure are found at all ages. Affected brain-related functions include perceptual and sensory information processing, intellectual and cognitive development, memory and executive functions, emotion and self-regulation, and academic achievement. Correspondingly, with the breakdown of natural barriers against entry and translocation of toxic particles in the brain, the most common structural changes are responses promoting neuroinflammation and indicating early neurodegenerative processes. In spite of the gaps in current scientific knowledge and the challenges posed by non-scientific issues that influence policy, the evidence invites the conclusion that urban outdoor air pollution is a serious threat to healthy brain development which may set the conditions for neurodegenerative diseases. Such evidence supports the perspective that urgent strategic precautionary actions, minimizing exposure and attenuating its effects, are needed to protect children and their brain development. PMID:29670873

Gangliosides and Ceramides Change in a Mouse Model of Blast Induced Traumatic Brain Injury

PubMed Central

2013-01-01

Explosive detonations generate atmospheric pressure changes that produce nonpenetrating blast induced “mild” traumatic brain injury (bTBI). The structural basis for mild bTBI has been extremely controversial. The present study applies matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging to track the distribution of gangliosides in mouse brain tissue that were exposed to very low level of explosive detonations (2.5–5.5 psi peak overpressure). We observed major increases of the ganglioside GM2 in the hippocampus, thalamus, and hypothalamus after a single blast exposure. Moreover, these changes were accompanied by depletion of ceramides. No neurological or brain structural signs of injury could be inferred using standard light microscopic techniques. The first source of variability is generated by the Latency between blast and tissue sampling (peak intensity of the blast wave). These findings suggest that subtle molecular changes in intracellular membranes and plasmalemma compartments may be biomarkers for biological responses to mild bTBI. This is also the first report of a GM2 increase in the brains of mature mice from a nongenetic etiology. PMID:23590251

Experimental evidence for improved neuroimaging interpretation using three-dimensional graphic models.

PubMed

Ruisoto, Pablo; Juanes, Juan Antonio; Contador, Israel; Mayoral, Paula; Prats-Galino, Alberto

2012-01-01

Three-dimensional (3D) or volumetric visualization is a useful resource for learning about the anatomy of the human brain. However, the effectiveness of 3D spatial visualization has not yet been assessed systematically. This report analyzes whether 3D volumetric visualization helps learners to identify and locate subcortical structures more precisely than classical cross-sectional images based on a two dimensional (2D) approach. Eighty participants were assigned to each experimental condition: 2D cross-sectional visualization vs. 3D volumetric visualization. Both groups were matched for age, gender, visual-spatial ability, and previous knowledge of neuroanatomy. Accuracy in identifying brain structures, execution time, and level of confidence in the response were taken as outcome measures. Moreover, interactive effects between the experimental conditions (2D vs. 3D) and factors such as level of competence (novice vs. expert), image modality (morphological and functional), and difficulty of the structures were analyzed. The percentage of correct answers (hit rate) and level of confidence in responses were significantly higher in the 3D visualization condition than in the 2D. In addition, the response time was significantly lower for the 3D visualization condition in comparison with the 2D. The interaction between the experimental condition (2D vs. 3D) and difficulty was significant, and the 3D condition facilitated the location of difficult images more than the 2D condition. 3D volumetric visualization helps to identify brain structures such as the hippocampus and amygdala, more accurately and rapidly than conventional 2D visualization. This paper discusses the implications of these results with regards to the learning process involved in neuroimaging interpretation. Copyright © 2012 American Association of Anatomists.

The effect of competitive and non-competitive NMDA receptor antagonists, ACPC and MK-801 on NPY and CRF-like immunoreactivity in the rat brain amygdala.

PubMed

Wierońska, J M; Brański, P; Pałvcha, A; Smiałowska, M

2001-01-01

Amygdala is the brain structure responsible for integrating all behavior connected with fear, and in this structure two neuropeptides, neuropeptide Y (NPY), corticoliberin (CRF) and the most abundant excitatory neurotransmitter glutamate seem to take part in the regulation of anxiety behavior. Our previous studies showed the modulation of NPY and CRF expression by classical neurotransmitters in some brain structures, therefore in the present study we investigated the effect of NMDA receptor antagonists on the expression of NPY and CRF immunoreactivity in the rat brain amygdala. A non-competitive NMDA receptor antagonist, MK-801, or a functional NMDA antagonist, ACPC were used. Brains were taken out and processed by immunohistochemical method using specific NPY or CRF antibodies. The staining intensity and density of IR neurons were evaluated under a microscope in amygdala sections. It was found that both MK-801 and ACPC induced a significant decrease in NPY-immunoreactivity in amygdala nerve cell bodies and terminals, which may suggest an increased release of this peptide. CRF-IR was decreased after ACPC only. The obtained results indicate that in the amygdala, the NMDA receptors mediated glutamatergic transmission may regulate NPY neurons. Copyright 2001 Harcourt Publishers Ltd.

Genetics, Cognition, and Neurobiology of Schizotypal Personality: A Review of the Overlap with Schizophrenia

PubMed Central

Ettinger, Ulrich; Meyhöfer, Inga; Steffens, Maria; Wagner, Michael; Koutsouleris, Nikolaos

2013-01-01

Schizotypy refers to a set of temporally stable traits that are observed in the general population and that resemble the signs and symptoms of schizophrenia. Here, we review evidence from studies on genetics, cognition, perception, motor and oculomotor control, brain structure, brain function, and psychopharmacology in schizotypy. We specifically focused on identifying areas of overlap between schizotypy and schizophrenia. Evidence was corroborated that significant overlap exists between the two, covering the behavioral brain structural and functional as well molecular levels. In particular, several studies showed that individuals with high levels of schizotypal traits exhibit alterations in neurocognitive task performance and underlying brain function similar to the deficits seen in patients with schizophrenia. Studies of brain structure have shown both volume reductions and increase in schizotypy, pointing to schizophrenia-like deficits as well as possible protective or compensatory mechanisms. Experimental pharmacological studies have shown that high levels of schizotypy are associated with (i) enhanced dopaminergic response in striatum following administration of amphetamine and (ii) improvement of cognitive performance following administration of antipsychotic compounds. Together, this body of work suggests that schizotypy shows overlap with schizophrenia across multiple behavioral and neurobiological domains, suggesting that the study of schizotypal traits may be useful in improving our understanding of the etiology of schizophrenia. PMID:24600411

Psychotic Experiences, Working Memory, and the Developing Brain: A Multimodal Neuroimaging Study

PubMed Central

Fonville, Leon; Cohen Kadosh, Kathrin; Drakesmith, Mark; Dutt, Anirban; Zammit, Stanley; Mollon, Josephine; Reichenberg, Abraham; Lewis, Glyn; Jones, Derek K.; David, Anthony S.

2015-01-01

Psychotic experiences (PEs) occur in the general population, especially in children and adolescents, and are associated with poor psychosocial outcomes, impaired cognition, and increased risk of transition to psychosis. It is unknown how the presence and persistence of PEs during early adulthood affects cognition and brain function. The current study assessed working memory as well as brain function and structure in 149 individuals, with and without PEs, drawn from a population cohort. Observer-rated PEs were classified as persistent or transient on the basis of longitudinal assessments. Working memory was assessed using the n-back task during fMRI. Dynamic causal modeling (DCM) was used to characterize frontoparietal network configuration and voxel-based morphometry was utilized to examine gray matter. Those with persistent, but not transient, PEs performed worse on the n-back task, compared with controls, yet showed no significant differences in regional brain activation or brain structure. DCM analyses revealed greater emphasis on frontal connectivity within a frontoparietal network in those with PEs compared with controls. We propose that these findings portray an altered configuration of working memory function in the brain, potentially indicative of an adaptive response to atypical development associated with the manifestation of PEs. PMID:26286920

Brain injury and discrimination: Two competing models-perceptions of responsibility and dangerousness.

PubMed

Foster, Lynette A; Leathem, Janet M; Humphries, Steve

2016-01-01

(1) To examine whether the willingness of people to socialize with adolescents with brain injury is influenced by gender, visibility of injury and/or knowing how to interact with people with brain injury; and (2) To consider two models: the responsibility model (attributions about the cause of a condition) and the danger appraisal model (perceptions of dangerousness due to anger/aggression) for their effect on willingness to socialize and to understand how these perceptions lead to avoidant behaviour. Participants were recruited either by personal approach or via Facebook advertising and completed a survey after reading a brief vignette and seeing a photo of an adolescent male or female, with or without a head scar. Vignettes for some participants were varied to represent perceptions of responsibility and dangerousness Main outcomes and results: ANOVAs and structural equation modelling revealed that participants were more willing to socialize with the adolescents with a scar than with no scar. Knowledge about how to interact with survivors impacted willingness to socialize, but familiarity did not. The full danger appraisal model was supported, but only some aspects of the responsibility model were supported. The results provide useful information for rehabilitation health professionals working with survivors of brain injury. The implications of these findings are discussed with regards to assisting adolescents' re-entry into society post-injury.

Characterizing the Associative Content of Brain Structures Involved in Habitual and Goal-Directed Actions in Humans: A Multivariate fMRI Study

PubMed Central

Liljeholm, Mimi; Zika, Ondrej; O'Doherty, John P.

2015-01-01

While there is accumulating evidence for the existence of distinct neural systems supporting goal-directed and habitual action selection in the mammalian brain, much less is known about the nature of the information being processed in these different brain regions. Associative learning theory predicts that brain systems involved in habitual control, such as the dorsolateral striatum, should contain stimulus and response information only, but not outcome information, while regions involved in goal-directed action, such as ventromedial and dorsolateral prefrontal cortex and dorsomedial striatum, should be involved in processing information about outcomes as well as stimuli and responses. To test this prediction, human participants underwent fMRI while engaging in a binary choice task designed to enable the separate identification of these different representations with a multivariate classification analysis approach. Consistent with our predictions, the dorsolateral striatum contained information about responses but not outcomes at the time of an initial stimulus, while the regions implicated in goal-directed action selection contained information about both responses and outcomes. These findings suggest that differential contributions of these regions to habitual and goal-directed behavioral control may depend in part on basic differences in the type of information that these regions have access to at the time of decision making. PMID:25740507

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

PubMed

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

2017-08-28

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

Nonparametric Hierarchical Bayesian Model for Functional Brain Parcellation

PubMed Central

Lashkari, Danial; Sridharan, Ramesh; Vul, Edward; Hsieh, Po-Jang; Kanwisher, Nancy; Golland, Polina

2011-01-01

We develop a method for unsupervised analysis of functional brain images that learns group-level patterns of functional response. Our algorithm is based on a generative model that comprises two main layers. At the lower level, we express the functional brain response to each stimulus as a binary activation variable. At the next level, we define a prior over the sets of activation variables in all subjects. We use a Hierarchical Dirichlet Process as the prior in order to simultaneously learn the patterns of response that are shared across the group, and to estimate the number of these patterns supported by data. Inference based on this model enables automatic discovery and characterization of salient and consistent patterns in functional signals. We apply our method to data from a study that explores the response of the visual cortex to a collection of images. The discovered profiles of activation correspond to selectivity to a number of image categories such as faces, bodies, and scenes. More generally, our results appear superior to the results of alternative data-driven methods in capturing the category structure in the space of stimuli. PMID:21841977

Communication in neuronal networks.

PubMed

Laughlin, Simon B; Sejnowski, Terrence J

2003-09-26

Brains perform with remarkable efficiency, are capable of prodigious computation, and are marvels of communication. We are beginning to understand some of the geometric, biophysical, and energy constraints that have governed the evolution of cortical networks. To operate efficiently within these constraints, nature has optimized the structure and function of cortical networks with design principles similar to those used in electronic networks. The brain also exploits the adaptability of biological systems to reconfigure in response to changing needs.

Motivational deficits after brain injury: effects of bromocriptine in 11 patients.

PubMed Central

Powell, J H; al-Adawi, S; Morgan, J; Greenwood, R J

1996-01-01

OBJECTIVE: To test the hypothesis that treatment with bromocriptine would ameliorate deficits in clinical motivation, responsiveness to reward, and frontal cognitive function after brain injury. METHOD: An open trial in six men and five women who had had either traumatic brain injury or subarachnoid haemorrhage between two months and five years previously. After repeated baseline assessments, bromocriptine was given in gradually increasing doses. Assessments were repeated at increasing doses, during maintenance, and after withdrawal. Novel structured instruments for quantifying motivation were developed; measures of anxiety and depression, and cognitive tests sensitive to motivation or frontal lobe involvement were also given. RESULTS: Bromocriptine treatment was followed by improved scores on all measures other than mood. Improvement was maintained after bromocriptine withdrawal in eight of the patients. CONCLUSION: Poor motivation in patients with brain injury may result from dysfunction in the mesolimbic/mesocortical dopaminergic circuitry, giving rise to associated deficiencies in reward responsiveness and frontal cognitive function. PMID:8774407

Effects of Long-Term Treatment on Brain Volume in Patients with Obstructive Sleep Apnea Syndrome

PubMed Central

Kim, Hosung; Joo, Eun Yeon; Suh, Sooyeon; Kim, Jae-Hun; Kim, Sung Tae; Hong, Seung Bong

2015-01-01

We assessed structural brain damage in obstructive sleep apnea syndrome (OSA) patients (21 males) and the effects of long-term continuous positive airway pressure (CPAP) treatment (18.2 ± 12.4 months; 8-44 months) on brain structures and investigated the relationship between severity of OSA and effects of treatment. Using deformation-based morphometry to measure local volume changes, we identified widespread neocortical and cerebellar atrophy in untreated patients compared to controls (59 males; Cohen's D = 0.6; FDR < 0.05). Analysis of longitudinally scanned magnetic resonance imaging (MRI) scans both before and after treatment showed increased brain volume following treatment (FDR < 0.05). Volume increase was correlated with longer treatment in the cortical areas that largely overlapped with the initial atrophy. The areas overlying the hippocampal dentate gyrus and the cerebellar dentate nucleus displayed a volume increase after treatment. Patients with very severe OSA (AHI > 64) presented with prefrontal atrophy and displayed an additional volume increase in this area following treatment. Higher impairment of working memory in patients prior to treatment correlated with prefrontal volume increase after treatment. The large overlap between the initial brain damage and the extent of recovery after treatment suggests partial recovery of non-permanent structural damage. Volume increases in the dentate gyrus and the dentate nucleus possibly likely indicate compensatory neurogenesis in response to diminishing oxidative stress. Such changes in other brain structures may explain gliosis, dendritic volume increase, or inflammation. This study provides neuroimaging evidence that revealed the positive effects of long-term CPAP treatment in patients with OSA. PMID:26503297

Impulsivity-based thrifty eating phenotype and the protective role of n-3 PUFAs intake in adolescents.

PubMed

Reis, R S; Dalle Molle, R; Machado, T D; Mucellini, A B; Rodrigues, D M; Bortoluzzi, A; Bigonha, S M; Toazza, R; Salum, G A; Minuzzi, L; Buchweitz, A; Franco, A R; Pelúzio, M C G; Manfro, G G; Silveira, P P

2016-03-15

The goal of the present study was to investigate whether intrauterine growth restriction (IUGR) affects brain responses to palatable foods and whether docosahexaenoic acid (DHA, an omega-3 fatty acid that is a primary structural component of the human brain) serum levels moderate the association between IUGR and brain and behavioral responses to palatable foods. Brain responses to palatable foods were investigated using a functional magnetic resonance imaging task in which participants were shown palatable foods, neutral foods and non-food items. Serum DHA was quantified in blood samples, and birth weight ratio (BWR) was used as a proxy for IUGR. The Dutch Eating Behavior Questionnaire (DEBQ) was used to evaluate eating behaviors. In the contrast palatable food > neutral items, we found an activation in the right superior frontal gyrus with BWR as the most important predictor; the lower the BWR (indicative of IUGR), the greater the activation of this region involved in impulse control/decision making facing the viewing of palatable food pictures versus neutral items. At the behavioral level, a general linear model predicting external eating using the DEBQ showed a significant interaction between DHA and IUGR status; in IUGR individuals, the higher the serum DHA, the lower is external eating. In conclusion, we suggest that IUGR moderates brain responses when facing stimuli related to palatable foods, activating an area related to impulse control. Moreover, higher intake of n-3 PUFAs can protect IUGR individuals from developing inappropriate eating behaviors, the putative mechanism of protection would involve decreasing intake in response to external food cues in adolescents/young adults.

Impulsivity-based thrifty eating phenotype and the protective role of n-3 PUFAs intake in adolescents

PubMed Central

Reis, R S; Dalle Molle, R; Machado, T D; Mucellini, A B; Rodrigues, D M; Bortoluzzi, A; Bigonha, S M; Toazza, R; Salum, G A; Minuzzi, L; Buchweitz, A; Franco, A R; Pelúzio, M C G; Manfro, G G; Silveira, P P

2016-01-01

The goal of the present study was to investigate whether intrauterine growth restriction (IUGR) affects brain responses to palatable foods and whether docosahexaenoic acid (DHA, an omega-3 fatty acid that is a primary structural component of the human brain) serum levels moderate the association between IUGR and brain and behavioral responses to palatable foods. Brain responses to palatable foods were investigated using a functional magnetic resonance imaging task in which participants were shown palatable foods, neutral foods and non-food items. Serum DHA was quantified in blood samples, and birth weight ratio (BWR) was used as a proxy for IUGR. The Dutch Eating Behavior Questionnaire (DEBQ) was used to evaluate eating behaviors. In the contrast palatable food > neutral items, we found an activation in the right superior frontal gyrus with BWR as the most important predictor; the lower the BWR (indicative of IUGR), the greater the activation of this region involved in impulse control/decision making facing the viewing of palatable food pictures versus neutral items. At the behavioral level, a general linear model predicting external eating using the DEBQ showed a significant interaction between DHA and IUGR status; in IUGR individuals, the higher the serum DHA, the lower is external eating. In conclusion, we suggest that IUGR moderates brain responses when facing stimuli related to palatable foods, activating an area related to impulse control. Moreover, higher intake of n-3 PUFAs can protect IUGR individuals from developing inappropriate eating behaviors, the putative mechanism of protection would involve decreasing intake in response to external food cues in adolescents/young adults. PMID:26978737

Effects of Ethanol on Brain Extracellular Matrix: Implications for Alcohol Use Disorder.

PubMed

Lasek, Amy W

2016-10-01

The brain extracellular matrix (ECM) occupies the space between cells and is involved in cell-matrix and cell-cell adhesion. However, in addition to providing structural support to brain tissue, the ECM activates cell signaling and controls synaptic transmission. The expression and activity of brain ECM components are regulated by alcohol exposure. This review will discuss what is currently known about the effects of alcohol on the activity and expression of brain ECM components. An interpretation of how these changes might promote alcohol use disorder (AUD) will be also provided. Ethanol (EtOH) exposure decreases levels of structural proteins involved in the interstitial matrix and basement membrane, with a concomitant increase in proteolytic enzymes that degrade these components. In contrast, EtOH exposure generally increases perineuronal net components. Because the ECM has been shown to regulate both synaptic plasticity and behavioral responses to drugs of abuse, regulation of the brain ECM by alcohol may be relevant to the development of alcoholism. Although investigation of the function of brain ECM in alcohol abuse is still in early stages, a greater understanding of the interplay between ECM and alcohol might lead to novel therapeutic strategies for treating AUD. Copyright © 2016 by the Research Society on Alcoholism.

Long-term effects of marijuana use on the brain

PubMed Central

Filbey, Francesca M.; Aslan, Sina; Calhoun, Vince D.; Spence, Jeffrey S.; Damaraju, Eswar; Caprihan, Arvind; Segall, Judith

2014-01-01

Questions surrounding the effects of chronic marijuana use on brain structure continue to increase. To date, however, findings remain inconclusive. In this comprehensive study that aimed to characterize brain alterations associated with chronic marijuana use, we measured gray matter (GM) volume via structural MRI across the whole brain by using voxel-based morphology, synchrony among abnormal GM regions during resting state via functional connectivity MRI, and white matter integrity (i.e., structural connectivity) between the abnormal GM regions via diffusion tensor imaging in 48 marijuana users and 62 age- and sex-matched nonusing controls. The results showed that compared with controls, marijuana users had significantly less bilateral orbitofrontal gyri volume, higher functional connectivity in the orbitofrontal cortex (OFC) network, and higher structural connectivity in tracts that innervate the OFC (forceps minor) as measured by fractional anisotropy (FA). Increased OFC functional connectivity in marijuana users was associated with earlier age of onset. Lastly, a quadratic trend was observed suggesting that the FA of the forceps minor tract initially increased following regular marijuana use but decreased with protracted regular use. This pattern may indicate differential effects of initial and chronic marijuana use that may reflect complex neuroadaptive processes in response to marijuana use. Despite the observed age of onset effects, longitudinal studies are needed to determine causality of these effects. PMID:25385625

Increased gray matter volume in the right angular and posterior parahippocampal gyri in loving-kindness meditators.

PubMed

Leung, Mei-Kei; Chan, Chetwyn C H; Yin, Jing; Lee, Chack-Fan; So, Kwok-Fai; Lee, Tatia M C

2013-01-01

Previous voxel-based morphometry (VBM) studies have revealed that meditation is associated with structural brain changes in regions underlying cognitive processes that are required for attention or mindfulness during meditation. This VBM study examined brain changes related to the practice of an emotion-oriented meditation: loving-kindness meditation (LKM). A 3 T magnetic resonance imaging (MRI) scanner captured images of the brain structures of 25 men, 10 of whom had practiced LKM in the Theravada tradition for at least 5 years. Compared with novices, more gray matter volume was detected in the right angular and posterior parahippocampal gyri in LKM experts. The right angular gyrus has not been previously reported to have structural differences associated with meditation, and its specific role in mind and cognitive empathy theory suggests the uniqueness of this finding for LKM practice. These regions are important for affective regulation associated with empathic response, anxiety and mood. At the same time, gray matter volume in the left temporal lobe in the LKM experts appeared to be greater, an observation that has also been reported in previous MRI meditation studies on meditation styles other than LKM. Overall, the findings of our study suggest that experience in LKM may influence brain structures associated with affective regulation.

The Involvement of Endogenous Neural Oscillations in the Processing of Rhythmic Input: More Than a Regular Repetition of Evoked Neural Responses

PubMed Central

Zoefel, Benedikt; ten Oever, Sanne; Sack, Alexander T.

2018-01-01

It is undisputed that presenting a rhythmic stimulus leads to a measurable brain response that follows the rhythmic structure of this stimulus. What is still debated, however, is the question whether this brain response exclusively reflects a regular repetition of evoked responses, or whether it also includes entrained oscillatory activity. Here we systematically present evidence in favor of an involvement of entrained neural oscillations in the processing of rhythmic input while critically pointing out which questions still need to be addressed before this evidence could be considered conclusive. In this context, we also explicitly discuss the potential functional role of such entrained oscillations, suggesting that these stimulus-aligned oscillations reflect, and serve as, predictive processes, an idea often only implicitly assumed in the literature. PMID:29563860

Maternal interpersonal affiliation is associated with adolescents' brain structure and reward processing

PubMed Central

Schneider, S; Brassen, S; Bromberg, U; Banaschewski, T; Conrod, P; Flor, H; Gallinat, J; Garavan, Hugh; Heinz, A; Martinot, J-L; Nees, F; Rietschel, M; Smolka, M N; Ströhle, A; Struve, M; Schumann, G; Büchel, C

2012-01-01

Considerable animal and human research has been dedicated to the effects of parenting on structural brain development, focusing on hippocampal and prefrontal areas. Conversely, although functional imaging studies suggest that the neural reward circuitry is involved in parental affection, little is known about mothers' interpersonal qualities in relation to their children's brain structure and function. Moreover, gender differences concerning the effect of maternal qualities have rarely been investigated systematically. In 63 adolescents, we assessed structural and functional magnetic resonance imaging as well as interpersonal affiliation in their mothers. This allowed us to associate maternal affiliation with gray matter density and neural responses during different phases of the well-established Monetary Incentive Delay task. Maternal affiliation was positively associated with hippocampal and orbitofrontal gray matter density. Moreover, in the feedback of reward hit as compared with reward miss, an association with caudate activation was found. Although no significant gender effects were observed in these associations, during reward feedback as compared with baseline, maternal affiliation was significantly associated with ventral striatal and caudate activation only in females. Our findings demonstrate that maternal interpersonal affiliation is related to alterations in both the brain structure and reward-related activation in healthy adolescents. Importantly, the pattern is in line with typical findings in depression and post-traumatic stress disorder, suggesting that a lack of maternal affiliation might have a role in the genesis of mental disorders. PMID:23149446

Decoding the dynamic representation of musical pitch from human brain activity.

PubMed

Sankaran, N; Thompson, W F; Carlile, S; Carlson, T A

2018-01-16

In music, the perception of pitch is governed largely by its tonal function given the preceding harmonic structure of the music. While behavioral research has advanced our understanding of the perceptual representation of musical pitch, relatively little is known about its representational structure in the brain. Using Magnetoencephalography (MEG), we recorded evoked neural responses to different tones presented within a tonal context. Multivariate Pattern Analysis (MVPA) was applied to "decode" the stimulus that listeners heard based on the underlying neural activity. We then characterized the structure of the brain's representation using decoding accuracy as a proxy for representational distance, and compared this structure to several well established perceptual and acoustic models. The observed neural representation was best accounted for by a model based on the Standard Tonal Hierarchy, whereby differences in the neural encoding of musical pitches correspond to their differences in perceived stability. By confirming that perceptual differences honor those in the underlying neuronal population coding, our results provide a crucial link in understanding the cognitive foundations of musical pitch across psychological and neural domains.

The Brain Basis for Misophonia.

PubMed

Kumar, Sukhbinder; Tansley-Hancock, Olana; Sedley, William; Winston, Joel S; Callaghan, Martina F; Allen, Micah; Cope, Thomas E; Gander, Phillip E; Bamiou, Doris-Eva; Griffiths, Timothy D

2017-02-20

Misophonia is an affective sound-processing disorder characterized by the experience of strong negative emotions (anger and anxiety) in response to everyday sounds, such as those generated by other people eating, drinking, chewing, and breathing [1-8]. The commonplace nature of these sounds (often referred to as "trigger sounds") makes misophonia a devastating disorder for sufferers and their families, and yet nothing is known about the underlying mechanism. Using functional and structural MRI coupled with physiological measurements, we demonstrate that misophonic subjects show specific trigger-sound-related responses in brain and body. Specifically, fMRI showed that in misophonic subjects, trigger sounds elicit greatly exaggerated blood-oxygen-level-dependent (BOLD) responses in the anterior insular cortex (AIC), a core hub of the "salience network" that is critical for perception of interoceptive signals and emotion processing. Trigger sounds in misophonics were associated with abnormal functional connectivity between AIC and a network of regions responsible for the processing and regulation of emotions, including ventromedial prefrontal cortex (vmPFC), posteromedial cortex (PMC), hippocampus, and amygdala. Trigger sounds elicited heightened heart rate (HR) and galvanic skin response (GSR) in misophonic subjects, which were mediated by AIC activity. Questionnaire analysis showed that misophonic subjects perceived their bodies differently: they scored higher on interoceptive sensibility than controls, consistent with abnormal functioning of AIC. Finally, brain structural measurements implied greater myelination within vmPFC in misophonic individuals. Overall, our results show that misophonia is a disorder in which abnormal salience is attributed to particular sounds based on the abnormal activation and functional connectivity of AIC. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Cross-frequency coupling in deep brain structures upon processing the painful sensory inputs.

PubMed

Liu, C C; Chien, J H; Kim, J H; Chuang, Y F; Cheng, D T; Anderson, W S; Lenz, F A

2015-09-10

Cross-frequency coupling has been shown to be functionally significant in cortical information processing, potentially serving as a mechanism for integrating functionally relevant regions in the brain. In this study, we evaluate the hypothesis that pain-related gamma oscillatory responses are coupled with low-frequency oscillations in the frontal lobe, amygdala and hippocampus, areas known to have roles in pain processing. We delivered painful laser pulses to random locations on the dorsal hand of five patients with uncontrolled epilepsy requiring depth electrode implantation for seizure monitoring. Two blocks of 40 laser stimulations were delivered to each subject and the pain-intensity was controlled at five in a 0-10 scale by adjusting the energy level of the laser pulses. Local-field-potentials (LFPs) were recorded through bilaterally implanted depth electrode contacts to study the oscillatory responses upon processing the painful laser stimulations. Our results show that painful laser stimulations enhanced low-gamma (LH, 40-70 Hz) and high-gamma (HG, 70-110 Hz) oscillatory responses in the amygdala and hippocampal regions on the right hemisphere and these gamma responses were significantly coupled with the phases of theta (4-7 Hz) and alpha (8-1 2 Hz) rhythms during pain processing. Given the roles of these deep brain structures in emotion, these findings suggest that the oscillatory responses in these regions may play a role in integrating the affective component of pain, which may contribute to our understanding of the mechanisms underlying the affective information processing in humans. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Imaging Live Drosophila Brain with Two-Photon Fluorescence Microscopy

NASA Astrophysics Data System (ADS)

Ahmed, Syeed Ehsan

Two-photon fluorescence microscopy is an imaging technique which delivers distinct benefits for in vivo cellular and molecular imaging. Cyclic adenosine monophosphate (cAMP), a second messenger molecule, is responsible for triggering many physiological changes in neural system. However, the mechanism by which this molecule regulates responses in neuron cells is not yet clearly understood. When cAMP binds to a target protein, it changes the structure of that protein. Therefore, studying this molecular structure change with fluorescence resonance energy transfer (FRET) imaging can shed light on the cAMP functioning mechanism. FRET is a non-radiative dipole-dipole coupling which is sensitive to small distance change in nanometer scale. In this study we have investigated the effect of dopamine in cAMP dynamics in vivo. In our study two-photon fluorescence microscope was used for imaging mushroom bodies inside live Drosophila melanogaster brain and we developed a method for studying the change in cyclic AMP level.

Neuroanatomy and Physiology of Brain Dysfunction in Sepsis.

PubMed

Mazeraud, Aurelien; Pascal, Quentin; Verdonk, Franck; Heming, Nicholas; Chrétien, Fabrice; Sharshar, Tarek

2016-06-01

Sepsis-associated encephalopathy (SAE), a complication of sepsis, is often complicated by acute and long-term brain dysfunction. SAE is associated with electroencephalogram pattern changes and abnormal neuroimaging findings. The major processes involved are neuroinflammation, circulatory dysfunction, and excitotoxicity. Neuroinflammation and microcirculatory alterations are diffuse, whereas excitotoxicity might occur in more specific structures involved in the response to stress and the control of vital functions. A dysfunction of the brainstem, amygdala, and hippocampus might account for the increased mortality, psychological disorders, and cognitive impairment. This review summarizes clinical and paraclinical features of SAE and describes its mechanisms at cellular and structural levels. Copyright © 2016 Elsevier Inc. All rights reserved.

Acute Neuroimmune Modulation Attenuates the Development of Anxiety-Like Freezing Behavior in an Animal Model of Traumatic Brain Injury

PubMed Central

Rodgers, Krista M.; Bercum, Florencia M.; McCallum, Danielle L.; Rudy, Jerry W.; Frey, Lauren C.; Johnson, Kirk W.; Watkins, Linda R.

2012-01-01

Abstract Chronic anxiety is a common and debilitating result of traumatic brain injury (TBI) in humans. While little is known about the neural mechanisms of this disorder, inflammation resulting from activation of the brain's immune response to insult has been implicated in both human post-traumatic anxiety and in recently developed animal models. In this study, we used a lateral fluid percussion injury (LFPI) model of TBI in the rat and examined freezing behavior as a measure of post-traumatic anxiety. We found that LFPI produced anxiety-like freezing behavior accompanied by increased reactive gliosis (reflecting neuroimmune inflammatory responses) in key brain structures associated with anxiety: the amygdala, insula, and hippocampus. Acute peri-injury administration of ibudilast (MN166), a glial cell activation inhibitor, suppressed both reactive gliosis and freezing behavior, and continued neuroprotective effects were apparent several months post-injury. These results support the conclusion that inflammation produced by neuroimmune responses to TBI play a role in post-traumatic anxiety, and that acute suppression of injury-induced glial cell activation may have promise for the prevention of post-traumatic anxiety in humans. PMID:22435644

Neural predictors of individual differences in response to math tutoring in primary-grade school children

PubMed Central

Supekar, Kaustubh; Swigart, Anna G.; Tenison, Caitlin; Jolles, Dietsje D.; Rosenberg-Lee, Miriam; Fuchs, Lynn; Menon, Vinod

2013-01-01

Now, more than ever, the ability to acquire mathematical skills efficiently is critical for academic and professional success, yet little is known about the behavioral and neural mechanisms that drive some children to acquire these skills faster than others. Here we investigate the behavioral and neural predictors of individual differences in arithmetic skill acquisition in response to 8-wk of one-to-one math tutoring. Twenty-four children in grade 3 (ages 8–9 y), a critical period for acquisition of basic mathematical skills, underwent structural and resting-state functional MRI scans pretutoring. A significant shift in arithmetic problem-solving strategies from counting to fact retrieval was observed with tutoring. Notably, the speed and accuracy of arithmetic problem solving increased with tutoring, with some children improving significantly more than others. Next, we examined whether pretutoring behavioral and brain measures could predict individual differences in arithmetic performance improvements with tutoring. No behavioral measures, including intelligence quotient, working memory, or mathematical abilities, predicted performance improvements. In contrast, pretutoring hippocampal volume predicted performance improvements. Furthermore, pretutoring intrinsic functional connectivity of the hippocampus with dorsolateral and ventrolateral prefrontal cortices and the basal ganglia also predicted performance improvements. Our findings provide evidence that individual differences in morphometry and connectivity of brain regions associated with learning and memory, and not regions typically involved in arithmetic processing, are strong predictors of responsiveness to math tutoring in children. More generally, our study suggests that quantitative measures of brain structure and intrinsic brain organization can provide a more sensitive marker of skill acquisition than behavioral measures. PMID:23630286

Neural predictors of individual differences in response to math tutoring in primary-grade school children.

PubMed

Supekar, Kaustubh; Swigart, Anna G; Tenison, Caitlin; Jolles, Dietsje D; Rosenberg-Lee, Miriam; Fuchs, Lynn; Menon, Vinod

2013-05-14

Now, more than ever, the ability to acquire mathematical skills efficiently is critical for academic and professional success, yet little is known about the behavioral and neural mechanisms that drive some children to acquire these skills faster than others. Here we investigate the behavioral and neural predictors of individual differences in arithmetic skill acquisition in response to 8-wk of one-to-one math tutoring. Twenty-four children in grade 3 (ages 8-9 y), a critical period for acquisition of basic mathematical skills, underwent structural and resting-state functional MRI scans pretutoring. A significant shift in arithmetic problem-solving strategies from counting to fact retrieval was observed with tutoring. Notably, the speed and accuracy of arithmetic problem solving increased with tutoring, with some children improving significantly more than others. Next, we examined whether pretutoring behavioral and brain measures could predict individual differences in arithmetic performance improvements with tutoring. No behavioral measures, including intelligence quotient, working memory, or mathematical abilities, predicted performance improvements. In contrast, pretutoring hippocampal volume predicted performance improvements. Furthermore, pretutoring intrinsic functional connectivity of the hippocampus with dorsolateral and ventrolateral prefrontal cortices and the basal ganglia also predicted performance improvements. Our findings provide evidence that individual differences in morphometry and connectivity of brain regions associated with learning and memory, and not regions typically involved in arithmetic processing, are strong predictors of responsiveness to math tutoring in children. More generally, our study suggests that quantitative measures of brain structure and intrinsic brain organization can provide a more sensitive marker of skill acquisition than behavioral measures.

Systematic Review of Prenatal Cocaine Exposure and Adolescent Development

PubMed Central

Buckingham-Howes, Stacy; Berger, Sarah Shafer; Scaletti, Laura A.

2013-01-01

BACKGROUND AND OBJECTIVE: Previous research found that prenatal cocaine exposure (PCE) may increase children's vulnerability to behavior and cognition problems. Maturational changes in brain and social development make adolescence an ideal time to reexamine associations. The objective was to conduct a systematic review of published studies examining associations between PCE and adolescent development (behavior, cognition/school outcomes, physiologic responses, and brain morphology/functioning). METHODS: Articles were obtained from PubMed, PsycInfo, Web of Science, and CINAHL databases through July 2012 with search terms: prenatal drug, substance, or cocaine exposure; adolescence/adolescent; and in utero substance/drug exposure. Criteria for inclusion were nonexposed comparison group, human adolescents aged 11 to 19, peer-reviewed, English-language, and adolescent outcomes. RESULTS: Twenty-seven studies representing 9 cohorts met the criteria. Four outcome categories were identified: behavior, cognition/school performance, brain structure/function, and physiologic responses. Eleven examined behavior; 7 found small but significant differences favoring nonexposed adolescents, with small effect sizes. Eight examined cognition/school performance; 6 reported significantly lower scores on language and memory tasks among adolescents with PCE, with varying effect sizes varied. Eight examined brain structure/function and reported morphologic differences with few functional differences. Three examined physiologic responses with discordant findings. Most studies controlled for other prenatal exposures, caregiving environment, and violence exposure; few examined mechanisms. CONCLUSIONS: Consistent with findings among younger children, PCE increases the risk for small but significantly less favorable adolescent functioning. Although the clinical importance of differences is often unknown, the caregiving environment and violence exposure pose additional threats. Future research should investigate mechanisms linking PCE with adolescent functioning. PMID:23713107

Neonatal neuroimaging: going beyond the pictures.

PubMed

Ramenghi, Luca A; Rutherford, Mary; Fumagalli, Monica; Bassi, Laura; Messner, Hubert; Counsell, Serena; Mosca, Fabio

2009-10-01

The cerebral ultrasound has been used many years for the diagnosis of brain lesions in term and preterm newborns. Major improvements were obtained by the combination of different imaging modalities such as Magnetic Resonance Imaging with the Diffusion Weighted Imaging (DWI) and the new quantitative Diffusion Tensor Imaging (DTI). The clinical use of MRI has been validated over some years especially to depict the perinatal asphyxia lesions in term newborns, but its use in order to diagnose the typical diseases of preterm babies is very recent and useful in identifying a marker able to predict neurological outcome. The imaging correlates for motor impairment are well recognized (periventricular white matter cavitations), but no any imaging correlate for cognitive impairment and neurobehavioral disorders. While DWI has been used in term newborns to identify the ischemic areas with restricted diffusion, it may be also used to characterize brain development in preterm infants with the Apparent Diffusion Coefficient (ADC) and may allow us to detect abnormalities responsible for the non-motor impairments. Recent datas showed that in infants without focal lesions higher ADC values in WM were associated with poorer neurodevelopmental assessment at 2 years. The DTI also allows to detect the Fractional Anisotropy (FA) that measures the microstructure. DTI can also be used to map the WM tracts in the immature brain and may be applied to understand the normal development or the response of the brain to injury. Some WM regions in the preterm brain have a lower FA suggesting that widespread WM abnormalities are present in preterms even in the absence of focal lesions. The complexity of the developing brain can be explained by the new tractography that can assess the connectivity of different WM regions and the association between structure and function, such as optic radiations microstructure and visual assessment score. Technological advances in neonatal brain imaging have made a major contribution to understand the neurobehavioral disorders of the developing brain that have the origin in the early structural cerebral organization and maturation.

Signaling pathways of interleukin-1 actions in the brain: anatomical distribution of phospho-ERK1/2 in the brain of rat treated systemically with interleukin-1beta.

PubMed

Nadjar, A; Combe, C; Busquet, P; Dantzer, R; Parnet, P

2005-01-01

Interleukin-1beta is released at the periphery during infection and acts on the nervous system to induce fever, neuroendocrine activation, and behavioral changes. These effects are mediated by brain type I IL-1 receptors. In vitro studies have shown the ability of interleukin-1beta to activate mitogen-activated protein kinase signaling pathways including p38, c-Jun N-terminal kinase and extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). In contrast to other mitogen-activated protein kinases, little is known about ERK1/2 activation in the rat brain in response to interleukin-1beta. The aim of the present study was therefore to investigate spatial and temporal activation of ERK1/2 in the rat brain after peripheral administration of interleukin-1beta using immunohistochemistry to detect the phosphorylated form of the kinase. In non-stimulated conditions, phosphorylated ERK1/2 immunoreactivity was observed in neurons throughout the brain. Administration of interleukin-1beta (60 microg/kg, i.p.) induced the phosphorylation of ERK1/2 in areas at the interface between brain and blood or cerebrospinal fluid: meninges, circumventricular organs, endothelial like cells of the blood vessels, and in brain nuclei involved in behavioral depression, fever and neuroendocrine activation: paraventricular nucleus of the hypothalamus, supraoptic nucleus, central amygdala and arcuate nucleus. Double labeling of phosphorylated ERK1/2 and cell markers revealed the expression of phosphorylated ERK1/2 in neurons, astrocytes and microglia. Since phosphorylated ERK1/2 was found in structures in which type I IL-1 receptor has already been identified as well as in structures lacking this receptor, activation of ERK1/2 is likely to occur in response to both direct and indirect action of interleukin-1beta on its target cells.

Assessing the marks of change: how psychotherapy alters the brain structure in women with borderline personality disorder

PubMed Central

Schmitt, Ruth; Winter, Dorina; Niedtfeld, Inga; Herpertz, Sabine C.; Schmahl, Christian

2018-01-01

Background There is increasing evidence that psychotherapy can alter the function of the brain of patients with borderline personality disorder (BPD). However, it is not known whether psychotherapy can also modify the brain structure of patients with BPD. Methods We used structural MRI data of female patients with BPD before and after participation in 12 weeks of residential dialectical behavioural therapy (DBT) and compared them to data from female patients with BPD who received treatment as usual (TAU). We applied voxel-based morphometry to study voxel-wise changes in grey matter volume over time. Results We included 31 patients in the DBT group and 17 in the TAU group. Patients receiving DBT showed an increase of grey matter volume in the anterior cingulate cortex, inferior frontal gyrus and superior temporal gyrus together with an alteration of grey matter volume in the angular gyrus and supramarginal gyrus compared with patients receiving TAU. Furthermore, therapy response correlated with increase of grey matter volume in the angular gyrus. Limitations Only women were investigated, and groups differed in size, medication (controlled for) and intensity of the treatment condition. Conclusion We found that DBT increased grey matter volume of brain regions that are critically implicated in emotion regulation and higher-order functions, such as mentalizing. The role of the angular gyrus for treatment response may reside in its cross-modal integrative function. These findings enhance our understanding of psychotherapy mechanisms of change and may foster the development of neurobiologically informed therapeutic interventions. PMID:29688873

Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

PubMed

Shoemaker, Ritchie C; House, Dennis; Ryan, James C

2014-01-01

Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB cases compared to 5% of controls, as well as elevated lactate and depressed ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases. This study used the volumetric software program NeuroQuant® (NQ) to determine specific brain structure volumes in consecutive patients (N=17) seen in a medical clinic specializing in inflammatory illness. Each of these patients presented for evaluation of an illness thought to be associated with exposure to WDB, and received an MRI that was evaluated by NQ. When compared to those of a medical control group (N=18), statistically significant differences in brain structure proportions were seen for patients in both hemispheres of two of the eleven brain regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum. In addition, the left amygdala and right forebrain were also enlarged. These volumetric abnormalities, in conjunction with concurrent abnormalities in inflammatory markers, suggest a model for structural brain injury in "mold illness" based on increased permeability of the blood-brain barrier due to chronic, systemic inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

Alterations in brain temperatures as a possible cause of migraine headache.

PubMed

Horváth, Csilla

2014-05-01

Migraine is a debilitating disease with a recurring generally unilateral headache and concomitant symptoms of nausea, vomiting and photo- and/or phonophobia that affects some 11-18% of the population. Most of the mechanisms previously put forward to explain the attacks have been questioned or give an explanation only some of the symptoms. Moreover, the best drugs for treatment are still the 20-year-old triptans, which have serious limitations as regards both efficacy and tolerability. As the dura and some cranial vessels are the only intracranial structures capable of pain sensations, a vascular theory of migraine emerged, but has been debated. Recent theories identified the hyperexcitability of structures involved in pain transmission, such as the trigeminal system or the cortex, or an abnormal modulatory function of the brainstem. However, there is ongoing scientific debate concerning these theories, neither of which is fully capable of explaining the occurrence of a migraine attack. The present article puts forward a hypothesis of the possibility of abnormal temperature regulation in certain regions or the overall brain in migraineurs, the attack being a defense mechanism to prevent neuronal damage. Few examinations have been made of temperature regulation in the human brain. It lacks the carotid rete, a vascular heat exchanger that serves in many animals to provide constant brain temperature. The human brain contains a high density of neurons with a considerable energy demand that is converted to heat. The human brain has a higher temperature than other parts of the body and needs continuous cooling. Recent studies revealed unexpectedly great variations in temperature of various structures of the brain and considerable changes in response to functional activation. There is various evidence in support of the hypothesis that accumulated heat in some structure or the overall brain may be behind the symptoms observed, such as a platelet abnormality, a decreased serotonin content, and dural "inflammation" including vasodilation and brainstem activation. The hypothesis postulates that a migraine attack serves to restore the brain temperature. Abnormally low temperatures in the brain can also result in headache. Surprisingly, no systematic examination of brain temperature changes in migraineurs has been published. Certain case reports support the present hypothesis. Various noninvasive technologies (e.g. MR) capable of monitoring brain temperature are available. If a systematic examination of local brain temperature revealed abnormalities in structures presumed to be involved in migraine, that would increase our understanding of the disease and trigger the development of improved treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neuroplasticity as a function of second language learning: anatomical changes in the human brain.

PubMed

Li, Ping; Legault, Jennifer; Litcofsky, Kaitlyn A

2014-09-01

The brain has an extraordinary ability to functionally and physically change or reconfigure its structure in response to environmental stimulus, cognitive demand, or behavioral experience. This property, known as neuroplasticity, has been examined extensively in many domains. But how does neuroplasticity occur in the brain as a function of an individual's experience with a second language? It is not until recently that we have gained some understanding of this question by examining the anatomical changes as well as functional neural patterns that are induced by the learning and use of multiple languages. In this article we review emerging evidence regarding how structural neuroplasticity occurs in the brain as a result of one's bilingual experience. Our review aims at identifying the processes and mechanisms that drive experience-dependent anatomical changes, and integrating structural imaging evidence with current knowledge of functional neural plasticity of language and other cognitive skills. The evidence reviewed so far portrays a picture that is highly consistent with structural neuroplasticity observed for other domains: second language experience-induced brain changes, including increased gray matter (GM) density and white matter (WM) integrity, can be found in children, young adults, and the elderly; can occur rapidly with short-term language learning or training; and are sensitive to age, age of acquisition, proficiency or performance level, language-specific characteristics, and individual differences. We conclude with a theoretical perspective on neuroplasticity in language and bilingualism, and point to future directions for research. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cerebral Developmental Abnormalities in a Mouse with Systemic Pyruvate Dehydrogenase Deficiency

PubMed Central

Pliss, Lioudmila; Hausknecht, Kathryn A.; Stachowiak, Michal K.; Dlugos, Cynthia A.; Richards, Jerry B.; Patel, Mulchand S.

2013-01-01

Pyruvate dehydrogenase (PDH) complex (PDC) deficiency is an inborn error of pyruvate metabolism causing a variety of neurologic manifestations. Systematic analyses of development of affected brain structures and the cellular processes responsible for their impairment have not been performed due to the lack of an animal model for PDC deficiency. METHODS: In the present study we investigated a murine model of systemic PDC deficiency by interrupting the X-linked Pdha1 gene encoding the α subunit of PDH to study its role on brain development and behavioral studies. RESULTS: Male embryos died prenatally but heterozygous females were born. PDC activity was reduced in the brain and other tissues in female progeny compared to age-matched control females. Immunohistochemical analysis of several brain regions showed that approximately 40% of cells were PDH−. The oxidation of glucose to CO2 and incorporation of glucose-carbon into fatty acids were reduced in brain slices from 15 day-old PDC-deficient females. Histological analyses showed alterations in several structures in white and gray matters in 35 day-old PDC-deficient females. Reduction in total cell number and reduced dendritic arbors in Purkinje neurons were observed in PDC-deficient females. Furthermore, cell proliferation, migration and differentiation into neurons by newly generated cells were reduced in the affected females during pre- and postnatal periods. PDC-deficient mice had normal locomotor activity in a novel environment but displayed decreased startle responses to loud noises and there was evidence of abnormal pre-pulse inhibition of the startle reflex. CONCLUSIONS: The results show that a reduction in glucose metabolism resulting in deficit in energy production and fatty acid biosynthesis impairs cellular differentiation and brain development in PDC-deficient mice. PMID:23840713

A Brain Network Processing the Age of Faces

PubMed Central

Homola, György A.; Jbabdi, Saad; Beckmann, Christian F.; Bartsch, Andreas J.

2012-01-01

Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships. PMID:23185334

Neural correlates of the self-concept in adolescence-A focus on the significance of friends.

PubMed

Romund, Lydia; Golde, Sabrina; Lorenz, Robert C; Raufelder, Diana; Pelz, Patricia; Gleich, Tobias; Heinz, Andreas; Beck, Anne

2017-02-01

The formation of a coherent and unified self-concept represents a key developmental stage during adolescence. Imaging studies on self-referential processing in adolescents are rare, and it is not clear whether neural structures involved in self-reflection are also involved in reflections of familiar others. In the current study, 41 adolescents were asked to make judgments about trait adjectives during functional magnetic resonance imaging (fMRI): they had to indicate whether the word describes themselves, their friends, their teachers or politicians. Findings indicate a greater overlap in neural networks for responses to self- and friend-related judgments compared to teachers and politicians. In particular, classic self-reference structures such as the ventromedial prefrontal cortex and medial posterior parietal cortex also exhibited higher activation to judgments about friends. In contrast, brain responses towards judgments of teachers (familiar others) compared to politicians (unfamiliar others) did not significantly differ. Results support behavioral findings of a greater relevance of friends for the development of a self-concept during adolescence and indicate underlying functional brain processes. Hum Brain Mapp 38:987-996, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Detecting and interpreting conscious experiences in behaviorally non-responsive patients.

PubMed

Naci, Lorina; Sinai, Leah; Owen, Adrian M

2017-01-15

Decoding the contents of consciousness from brain activity is one of the most challenging frontiers of cognitive neuroscience. The ability to interpret mental content without recourse to behavior is most relevant for understanding patients who may be demonstrably conscious, but entirely unable to speak or move willfully in any way, precluding any systematic investigation of their conscious experience. The lack of consistent behavioral responsivity engenders unique challenges to decoding any conscious experiences these patients may have solely based on their brain activity. For this reason, paradigms that have been successful in healthy individuals cannot serve to interpret conscious mental states in this patient group. Until recently, patient studies have used structured instructions to elicit willful modulation of brain activity according to command, in order to decode the presence of willful brain-based responses in this patient group. In recent work, we have used naturalistic paradigms, such as watching a movie or listening to an audio-story, to demonstrate that a common neural code supports conscious experiences in different individuals. Moreover, we have demonstrated that this code can be used to interpret the conscious experiences of a patient who had remained non-responsive for several years. This approach is easy to administer, brief, and does not require compliance with task instructions. Rather, it engages attention naturally through meaningful stimuli that are similar to the real-world sensory information in a patient's environment. Therefore, it may be particularly suited to probing consciousness and revealing residual brain function in highly impaired, acute, patients in a comatose state, thus helping to improve diagnostication and prognostication for this vulnerable patient group from the critical early stages of severe brain-injury. Copyright © 2015 Elsevier Inc. All rights reserved.

Serotonergic, Brain Volume and Attentional Correlates of Trait Anxiety in Primates

PubMed Central

Mikheenko, Yevheniia; Shiba, Yoshiro; Sawiak, Stephen; Braesicke, Katrin; Cockcroft, Gemma; Clarke, Hannah; Roberts, Angela C

2015-01-01

Trait anxiety is a risk factor for the development and maintenance of affective disorders, and insights into the underlying brain mechanisms are vital for improving treatment and prevention strategies. Translational studies in non-human primates, where targeted neurochemical and genetic manipulations can be made, are critical in view of their close neuroanatomical similarity to humans in brain regions implicated in trait anxiety. Thus, we characterised the serotonergic and regional brain volume correlates of trait-like anxiety in the marmoset monkey. Low- and high-anxious animals were identified by behavioral responses to a human intruder (HI) that are known to be sensitive to anxiolytic drug treatment. Extracellular serotonin levels within the amygdala were measured with in vivo microdialysis, at baseline and in response to challenge with the selective serotonin reuptake inhibitor, citalopram. Regional brain volume was assessed by structural magnetic resonance imaging. Anxious individuals showed persistent, long-term fearful responses to both a HI and a model snake, alongside sustained attention (vigilance) to novel cues in a context associated with unpredictable threat. Neurally, high-anxious marmosets showed reduced amygdala serotonin levels, and smaller volumes in a closely connected prefrontal region, the dorsal anterior cingulate cortex. These findings highlight behavioral and neural similarities between trait-like anxiety in marmosets and humans, and set the stage for further investigation of the processes contributing to vulnerability and resilience to affective disorders. PMID:25586542

Reduced evoked fos expression in activity-related brain regions in animal models of behavioral depression.

PubMed

Stone, Eric A; Lehmann, Michael L; Lin, Yan; Quartermain, David

2007-08-15

A previous study showed that two mouse models of behavioral depression, immune system activation and depletion of brain monoamines, are accompanied by marked reductions in stimulated neural activity in brain regions involved in motivated behavior. The present study tested whether this effect is common to other depression models by examining the effects of repeated forced swimming, chronic subordination stress or acute intraventricular galanin injection - three additional models - on baseline or stimulated c-fos expression in several brain regions known to be involved in motor or motivational processes (secondary motor, M2, anterior piriform cortex, APIR, posterior cingulate gyrus, CG, nucleus accumbens, NAC). Each of the depression models was found to reduce the fos response stimulated by exposure to a novel cage or a swim stress in all four of these brain areas but not to affect the response of a stress-sensitive region (paraventricular hypothalamus, PVH) that was included for control purposes. Baseline fos expression in these structures was either unaffected or affected in an opposite direction to the stimulated response. Pretreatment with either desmethylimipramine (DMI) or tranylcypromine (tranyl) attenuated these changes. It is concluded that the pattern of a reduced neural function of CNS motor/motivational regions with an increased function of stress areas is common to 5 models of behavioral depression in the mouse and is a potential experimental analog of the neural activity changes occurring in the clinical condition.

Impact of personality on the cerebral processing of emotional prosody.

PubMed

Brück, Carolin; Kreifelts, Benjamin; Kaza, Evangelia; Lotze, Martin; Wildgruber, Dirk

2011-09-01

While several studies have focused on identifying common brain mechanisms governing the decoding of emotional speech melody, interindividual variations in the cerebral processing of prosodic information, in comparison, have received only little attention to date: Albeit, for instance, differences in personality among individuals have been shown to modulate emotional brain responses, personality influences on the neural basis of prosody decoding have not been investigated systematically yet. Thus, the present study aimed at delineating relationships between interindividual differences in personality and hemodynamic responses evoked by emotional speech melody. To determine personality-dependent modulations of brain reactivity, fMRI activation patterns during the processing of emotional speech cues were acquired from 24 healthy volunteers and subsequently correlated with individual trait measures of extraversion and neuroticism obtained for each participant. Whereas correlation analysis did not indicate any link between brain activation and extraversion, strong positive correlations between measures of neuroticism and hemodynamic responses of the right amygdala, the left postcentral gyrus as well as medial frontal structures including the right anterior cingulate cortex emerged, suggesting that brain mechanisms mediating the decoding of emotional speech melody may vary depending on differences in neuroticism among individuals. Observed trait-specific modulations are discussed in the light of processing biases as well as differences in emotion control or task strategies which may be associated with the personality trait of neuroticism. Copyright © 2011 Elsevier Inc. All rights reserved.

Brain responses to verbal stimuli among multiple sclerosis patients with pseudobulbar affect.

PubMed

Haiman, Guy; Pratt, Hillel; Miller, Ariel

2008-08-15

To characterize the brain activity and associated cortical structures involved in pseudobulbar affect (PBA), a condition characterized by uncontrollable episodes of emotional lability in patients with multiple sclerosis (MS). Behavioral responses and event related potentials (ERP) in response to subjectively significant and neutral verbal stimuli were recorded from 33 subjects in 3 groups: 1) MS patients with PBA (MS+PBA); 2) MS patients without PBA (MS); 3) Healthy control subjects (HC). Statistical non-parametric mapping comparisons of ERP source current density distributions between groups were conducted separately for subjectively significant and for neutral stimuli. Behavioral responses showed more impulsive performance in patients with PBA. As expected, almost all ERP waveform comparisons between the MS groups and controls were significant. Source analysis indicated significantly distinct activation in MS+PBA in the vicinity of the somatosensory and motor areas in response to neutral stimuli, and at pre-motor and supplementary motor areas in response to subjectively significant stimuli. Both subjectively significant and neutral stimuli evoked higher current density in MS+PBA compared to both other groups. PBA of MS patients involves cortical structures related to sensory-motor and emotional processing, in addition to overactive involvement of motor cortical areas in response to neutral stimuli. These results may suggest that a 'disinhibition' of a "gate control"-type mechanism for emotional expression may lead to the lower emotional expression threshold of pseudobulbar affect.

Seeing responsibility: can neuroimaging teach us anything about moral and legal responsibility?

PubMed

Wasserman, David; Johnston, Josephine

2014-01-01

As imaging technologies help us understand the structure and function of the brain, providing insight into human capabilities as basic as vision and as complex as memory, and human conditions as impairing as depression and as fraught as psychopathy, some have asked whether they can also help us understand human agency. Specifically, could neuroimaging lead us to reassess the socially significant practice of assigning and taking responsibility? While responsibility itself is not a psychological process open to investigation through neuroimaging, decision-making is. Over the past decade, different researchers and scholars have sought to use neuroimaging (or the results of neuroimaging studies) to investigate what is going on in the brain when we make decisions. The results of this research raise the question whether neuroscience-especially now that it includes neuroimaging-can and should alter our understandings of responsibility and our related practice of holding people responsible. It is this question that we investigate here. © 2014 by The Hastings Center.

Adolescent rationality.

PubMed

Moshman, David

2013-01-01

Adolescents are commonly seen as irrational, a position supported to varying degrees by many developmentalists, who often appeal to recent research on adolescent brains. Careful review of relevant evidence, however, shows that (1) adults are less rational than is generally assumed, (2) adolescents (and adults) are categorically different from children with respect to the attainment of advanced levels of rationality and psychological functioning, and (3) adolescents and adults do not differ categorically from each other with respect to any rational competencies, irrational tendencies, brain structures, or neurological functioning. Development often continues in adolescence and beyond but categorical claims about adolescents as distinct from adults cannot be justified. A review of U.S. Supreme Court decisions concerning intellectual freedom, reproductive freedom, and criminal responsibility shows ongoing ambivalence and confusion about the rationality of adolescents. Developmental theory and research suggest that adolescents should be conceptualized as young adults, not immature brains, with important implications for their roles, rights, and responsibilities.

Human brain detects short-time nonlinear predictability in the temporal fine structure of deterministic chaotic sounds

NASA Astrophysics Data System (ADS)

Itoh, Kosuke; Nakada, Tsutomu

2013-04-01

Deterministic nonlinear dynamical processes are ubiquitous in nature. Chaotic sounds generated by such processes may appear irregular and random in waveform, but these sounds are mathematically distinguished from random stochastic sounds in that they contain deterministic short-time predictability in their temporal fine structures. We show that the human brain distinguishes deterministic chaotic sounds from spectrally matched stochastic sounds in neural processing and perception. Deterministic chaotic sounds, even without being attended to, elicited greater cerebral cortical responses than the surrogate control sounds after about 150 ms in latency after sound onset. Listeners also clearly discriminated these sounds in perception. The results support the hypothesis that the human auditory system is sensitive to the subtle short-time predictability embedded in the temporal fine structure of sounds.

Micromirror structured illumination microscope for high-speed in vivo drosophila brain imaging.

PubMed

Masson, A; Pedrazzani, M; Benrezzak, S; Tchenio, P; Preat, T; Nutarelli, D

2014-01-27

Genetic tools and especially genetically encoded fluorescent reporters have given a special place to optical microscopy in drosophila neurobiology research. In order to monitor neural networks activity, high speed and sensitive techniques, with high spatial resolution are required. Structured illumination microscopies are wide-field approaches with optical sectioning ability. Despite the large progress made with the introduction of the HiLo principle, they did not meet the criteria of speed and/or spatial resolution for drosophila brain imaging. We report on a new implementation that took advantage of micromirror matrix technology to structure the illumination. Thus, we showed that the developed instrument exhibits a spatial resolution close to that of confocal microscopy but it can record physiological responses with a speed improved by more than an order a magnitude.

The neural response properties and cortical organization of a rapidly adapting muscle sensory group response that overlaps with the frequencies that elicit the kinesthetic illusion.

PubMed

Marasco, Paul D; Bourbeau, Dennis J; Shell, Courtney E; Granja-Vazquez, Rafael; Ina, Jason G

2017-01-01

Kinesthesia is the sense of limb movement. It is fundamental to efficient motor control, yet its neurophysiological components remain poorly understood. The contributions of primary muscle spindles and cutaneous afferents to the kinesthetic sense have been well studied; however, potential contributions from muscle sensory group responses that are different than the muscle spindles have not been ruled out. Electrophysiological recordings in peripheral nerves and brains of male Sprague Dawley rats with a degloved forelimb preparation provide evidence of a rapidly adapting muscle sensory group response that overlaps with vibratory inputs known to generate illusionary perceptions of limb movement in humans (kinesthetic illusion). This group was characteristically distinct from type Ia muscle spindle fibers, the receptor historically attributed to limb movement sensation, suggesting that type Ia muscle spindle fibers may not be the sole carrier of kinesthetic information. The sensory-neural structure of muscles is complex and there are a number of possible sources for this response group; with Golgi tendon organs being the most likely candidate. The rapidly adapting muscle sensory group response projected to proprioceptive brain regions, the rodent homolog of cortical area 3a and the second somatosensory area (S2), with similar adaption and frequency response profiles between the brain and peripheral nerves. Their representational organization was muscle-specific (myocentric) and magnified for proximal and multi-articulate limb joints. Projection to proprioceptive brain areas, myocentric representational magnification of muscles prone to movement error, overlap with illusionary vibrational input, and resonant frequencies of volitional motor unit contraction suggest that this group response may be involved with limb movement processing.

The neural response properties and cortical organization of a rapidly adapting muscle sensory group response that overlaps with the frequencies that elicit the kinesthetic illusion

PubMed Central

Marasco, Paul D.; Bourbeau, Dennis J.; Shell, Courtney E.; Granja-Vazquez, Rafael; Ina, Jason G.

2017-01-01

Kinesthesia is the sense of limb movement. It is fundamental to efficient motor control, yet its neurophysiological components remain poorly understood. The contributions of primary muscle spindles and cutaneous afferents to the kinesthetic sense have been well studied; however, potential contributions from muscle sensory group responses that are different than the muscle spindles have not been ruled out. Electrophysiological recordings in peripheral nerves and brains of male Sprague Dawley rats with a degloved forelimb preparation provide evidence of a rapidly adapting muscle sensory group response that overlaps with vibratory inputs known to generate illusionary perceptions of limb movement in humans (kinesthetic illusion). This group was characteristically distinct from type Ia muscle spindle fibers, the receptor historically attributed to limb movement sensation, suggesting that type Ia muscle spindle fibers may not be the sole carrier of kinesthetic information. The sensory-neural structure of muscles is complex and there are a number of possible sources for this response group; with Golgi tendon organs being the most likely candidate. The rapidly adapting muscle sensory group response projected to proprioceptive brain regions, the rodent homolog of cortical area 3a and the second somatosensory area (S2), with similar adaption and frequency response profiles between the brain and peripheral nerves. Their representational organization was muscle-specific (myocentric) and magnified for proximal and multi-articulate limb joints. Projection to proprioceptive brain areas, myocentric representational magnification of muscles prone to movement error, overlap with illusionary vibrational input, and resonant frequencies of volitional motor unit contraction suggest that this group response may be involved with limb movement processing. PMID:29182648

Long-term reorganization of structural brain networks in a rabbit model of intrauterine growth restriction.

PubMed

Batalle, Dafnis; Muñoz-Moreno, Emma; Arbat-Plana, Ariadna; Illa, Miriam; Figueras, Francesc; Eixarch, Elisenda; Gratacos, Eduard

2014-10-15

Characterization of brain changes produced by intrauterine growth restriction (IUGR) is among the main challenges of modern fetal medicine and pediatrics. This condition affects 5-10% of all pregnancies and is associated with a wide range of neurodevelopmental disorders. Better understanding of the brain reorganization produced by IUGR opens a window of opportunity to find potential imaging biomarkers in order to identify the infants with a high risk of having neurodevelopmental problems and apply therapies to improve their outcomes. Structural brain networks obtained from diffusion magnetic resonance imaging (MRI) is a promising tool to study brain reorganization and to be used as a biomarker of neurodevelopmental alterations. In the present study this technique is applied to a rabbit animal model of IUGR, which presents some advantages including a controlled environment and the possibility to obtain high quality MRI with long acquisition times. Using a Q-Ball diffusion model, and a previously published rabbit brain MRI atlas, structural brain networks of 15 IUGR and 14 control rabbits at 70 days of age (equivalent to pre-adolescence human age) were obtained. The analysis of graph theory features showed a decreased network infrastructure (degree and binary global efficiency) associated with IUGR condition and a set of generalized fractional anisotropy (GFA) weighted measures associated with abnormal neurobehavior. Interestingly, when assessing the brain network organization independently of network infrastructure by means of normalized networks, IUGR showed increased global and local efficiencies. We hypothesize that this effect could reflect a compensatory response to reduced infrastructure in IUGR. These results present new evidence on the long-term persistence of the brain reorganization produced by IUGR that could underlie behavioral and developmental alterations previously described. The described changes in network organization have the potential to be used as biomarkers to monitor brain changes produced by experimental therapies in IUGR animal model. Copyright © 2014 Elsevier Inc. All rights reserved.

Erotic and disgust-inducing pictures--differences in the hemodynamic responses of the brain.

PubMed

Stark, Rudolf; Schienle, Anne; Girod, Cornelia; Walter, Bertram; Kirsch, Peter; Blecker, Carlo; Ott, Ulrich; Schäfer, Axel; Sammer, Gebhard; Zimmermann, Mark; Vaitl, Dieter

2005-09-01

The aim of this fMRI study was to explore brain structures that are involved in the processing of erotic and disgust-inducing pictures. The stimuli were chosen to trigger approach and withdrawal tendencies, respectively. By adding sadomasochistic (SM) scenes to the design and examining 12 subjects with and 12 subjects without sadomasochistic preferences, we introduced a picture category that induced erotic pleasure in one sample and disgust in the other sample. Since we also presented neutral pictures, all subjects viewed pictures of four different categories: neutral, disgust-inducing, erotic, and SM erotic pictures. The analysis indicated that several brain structures are commonly involved in the processing of disgust-inducing and erotic pictures (occipital cortex, hippocampus, thalamus, and the amygdala). The ventral striatum was specifically activated when subjects saw highly sexually arousing pictures. This indicates the involvement of the human reward system during the processing of visual erotica.

Dual-Targeting Lactoferrin-Conjugated Polymerized Magnetic Polydiacetylene-Assembled Nanocarriers with Self-Responsive Fluorescence/Magnetic Resonance Imaging for In Vivo Brain Tumor Therapy.

PubMed

Fang, Jen-Hung; Chiu, Tsung-Lang; Huang, Wei-Chen; Lai, Yen-Ho; Hu, Shang-Hsiu; Chen, You-Yin; Chen, San-Yuan

2016-03-01

Maintaining a high concentration of therapeutic agents in the brain is difficult due to the restrictions of the blood-brain barrier (BBB) and rapid removal from blood circulation. To enable controlled drug release and enhance the blood-brain barrier (BBB)-crossing efficiency for brain tumor therapy, a new dual-targeting magnetic polydiacetylene nanocarriers (PDNCs) delivery system modified with lactoferrin (Lf) is developed. The PDNCs are synthesized using the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid (PCDA) monomers through spontaneous assembling onto the surface of superparamagnetic iron oxide (SPIO) nanoparticles to form micelles-polymerized structures. The results demonstrate that PDNCs will reduce the drug leakage and further control the drug release, and display self-responsive fluorescence upon intracellular uptake for cell trafficking and imaging-guided tumor treatment. The magnetic Lf-modified PDNCs with magnetic resonance imaging (MRI) and dual-targeting ability can enhance the transportation of the PDNCs across the BBB for tracking and targeting gliomas. An enhanced therapeutic efficiency can be obtained using Lf-Cur (Curcumin)-PDNCs by improving the retention time of the encapsulated Cur and producing fourfold higher Cur amounts in the brain compared to free Cur. Animal studies also confirm that Lf targeting and controlled release act synergistically to significantly suppress tumors in orthotopic brain-bearing rats. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterizing the associative content of brain structures involved in habitual and goal-directed actions in humans: a multivariate FMRI study.

PubMed

McNamee, Daniel; Liljeholm, Mimi; Zika, Ondrej; O'Doherty, John P

2015-03-04

While there is accumulating evidence for the existence of distinct neural systems supporting goal-directed and habitual action selection in the mammalian brain, much less is known about the nature of the information being processed in these different brain regions. Associative learning theory predicts that brain systems involved in habitual control, such as the dorsolateral striatum, should contain stimulus and response information only, but not outcome information, while regions involved in goal-directed action, such as ventromedial and dorsolateral prefrontal cortex and dorsomedial striatum, should be involved in processing information about outcomes as well as stimuli and responses. To test this prediction, human participants underwent fMRI while engaging in a binary choice task designed to enable the separate identification of these different representations with a multivariate classification analysis approach. Consistent with our predictions, the dorsolateral striatum contained information about responses but not outcomes at the time of an initial stimulus, while the regions implicated in goal-directed action selection contained information about both responses and outcomes. These findings suggest that differential contributions of these regions to habitual and goal-directed behavioral control may depend in part on basic differences in the type of information that these regions have access to at the time of decision making. Copyright © 2015 the authors 0270-6474/15/353764-08$15.00/0.

Brain glucose metabolism during hypoglycemia in type 1 diabetes: insights from functional and metabolic neuroimaging studies.

PubMed

Rooijackers, Hanne M M; Wiegers, Evita C; Tack, Cees J; van der Graaf, Marinette; de Galan, Bastiaan E

2016-02-01

Hypoglycemia is the most frequent complication of insulin therapy in patients with type 1 diabetes. Since the brain is reliant on circulating glucose as its main source of energy, hypoglycemia poses a threat for normal brain function. Paradoxically, although hypoglycemia commonly induces immediate decline in cognitive function, long-lasting changes in brain structure and cognitive function are uncommon in patients with type 1 diabetes. In fact, recurrent hypoglycemia initiates a process of habituation that suppresses hormonal responses to and impairs awareness of subsequent hypoglycemia, which has been attributed to adaptations in the brain. These observations sparked great scientific interest into the brain's handling of glucose during (recurrent) hypoglycemia. Various neuroimaging techniques have been employed to study brain (glucose) metabolism, including PET, fMRI, MRS and ASL. This review discusses what is currently known about cerebral metabolism during hypoglycemia, and how findings obtained by functional and metabolic neuroimaging techniques contributed to this knowledge.

Deep brain stimulation of the subthalamic nucleus alters the cortical profile of response inhibition in the beta frequency band: a scalp EEG study in Parkinson's disease

PubMed Central

Swann, Nicole; Poizner, Howard; Houser, Melissa; Gould, Sherrie; Greenhouse, Ian; Cai, Weidong; Strunk, Jon; George, Jobi; Aron, Adam R

2011-01-01

Stopping an initiated response could be implemented by a fronto-basal-ganglia circuit, including the right inferior frontal cortex (rIFC) and the subthalamic nucleus (STN). Intracranial recording studies in humans reveal an increase in beta-band power (~16-20 Hz) within the rIFC and STN when a response is stopped. This suggests that the beta-band could be important for communication in this network. If this is the case, then altering one region should affect the electrophysiological response at the other. We addressed this hypothesis by recording scalp EEG during a stop task while modulating STN activity with deep brain stimulation. We studied 15 human patients with Parkinson's Disease and 15 matched healthy control subjects. Behaviorally, patients OFF stimulation were slower than controls to stop their response. Moreover, stopping speed was improved for ON compared to OFF stimulation. For scalp EEG, there was greater beta power, around the time of stopping, for patients ON compared to OFF stimulation. This effect was stronger over the right compared to left frontal cortex, consistent with the putative right-lateralization of the stopping network. Thus, deep brain stimulation of the STN improved behavioral stopping performance and increased the beta-band response over the right frontal cortex. These results complement other evidence for a structurally-connected, functional, circuit between right frontal cortex and the basal ganglia. The results also suggest that deep brain stimulation of the STN may improve task performance by increasing the fidelity of information transfer within a fronto-basal ganglia circuit. PMID:21490213

Traumatic Brain Injury: At the Crossroads of Neuropathology and Common Metabolic Endocrinopathies

PubMed Central

Li, Melanie

2018-01-01

Building on the seminal work by Geoffrey Harris in the 1970s, the neuroendocrinology field, having undergone spectacular growth, has endeavored to understand the mechanisms of hormonal connectivity between the brain and the rest of the body. Given the fundamental role of the brain in the orchestration of endocrine processes through interactions among neurohormones, it is thus not surprising that the structural and/or functional alterations following traumatic brain injury (TBI) can lead to endocrine changes affecting the whole organism. Taking into account that systemic hormones also act on the brain, modifying its structure and biochemistry, and can acutely and chronically affect several neurophysiological endpoints, the question is to what extent preexisting endocrine dysfunction may set the stage for an adverse outcome after TBI. In this review, we provide an overview of some aspects of three common metabolic endocrinopathies, e.g., diabetes mellitus, obesity, and thyroid dysfunction, and how these could be triggered by TBI. In addition, we discuss how the complex endocrine networks are woven into the responses to sudden changes after TBI, as well as some of the potential mechanisms that, separately or synergistically, can influence outcomes after TBI. PMID:29538298

Mesh electronics: a new paradigm for tissue-like brain probes.

PubMed

Hong, Guosong; Yang, Xiao; Zhou, Tao; Lieber, Charles M

2018-06-01

Existing implantable neurotechnologies for understanding the brain and treating neurological diseases have intrinsic properties that have limited their capability to achieve chronically-stable brain interfaces with single-neuron spatiotemporal resolution. These limitations reflect what has been dichotomy between the structure and mechanical properties of living brain tissue and non-living neural probes. To bridge the gap between neural and electronic networks, we have introduced the new concept of mesh electronics probes designed with structural and mechanical properties such that the implant begins to 'look and behave' like neural tissue. Syringe-implanted mesh electronics have led to the realization of probes that are neuro-attractive and free of the chronic immune response, as well as capable of stable long-term mapping and modulation of brain activity at the single-neuron level. This review provides a historical overview of a 10-year development of mesh electronics by highlighting the tissue-like design, syringe-assisted delivery, seamless neural tissue integration, and single-neuron level chronic recording stability of mesh electronics. We also offer insights on unique near-term opportunities and future directions for neuroscience and neurology that now are available or expected for mesh electronics neurotechnologies. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Ca2+-induced changes in the secondary structure of a 60 kDa phosphoinositide-specific phospholipase C from bovine brain cytosol.

PubMed Central

Herrero, C; Cornet, M E; Lopez, C; Barreno, P G; Municio, A M; Moscat, J

1988-01-01

The purification to homogeneity of a 60 kDa phosphoinositide-specific phospholipase C from bovine brain cytosol is reported here. This enzyme exhibits the same properties, in terms of response to Ca2+, as does the cytosolic activity in a variety of cell types. We show here that Ca2+ does not appear to modulate the binding of the enzyme to the substrate, but induces dramatic changes in its secondary structure. Therefore we suggest that a decrease in the alpha-helix content of this enzyme correlates with its ability to be activated by Ca2+. Images Fig. 1. PMID:2850798

[Effect of space flight factors simulated in ground-based experiments on the behavior, discriminant learning, and exchange of monoamines in different brain structures of rats].

PubMed

Shtemberg, A S; Lebedeva-Georgievskaia, K V; Matveeva, M I; Kudrin, V S; Narkevich, V B; Klodt, P M; Bazian, A S

2014-01-01

Experimental treatment (long-term fractionated γ-irradiation, antiorthostatic hypodynamia, and the combination of these factors) simulating the effect of space flight in ground-based experiments rapidly restored the motor and orienting-investigative activity of animals (rats) in "open-field" tests. The study of the dynamics of discriminant learning of rats of experimental groups did not show significant differences from the control animals. It was found that the minor effect of these factors on the cognitive performance of animals correlated with slight changes in the concentration ofmonoamines in the brain structures responsible for the cognitive, emotional, and motivational functions.

Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms

PubMed Central

Petzold, Anne; Valencia, Miguel; Pál, Balázs; Mena-Segovia, Juan

2015-01-01

Cholinergic neurons of the pedunculopontine nucleus (PPN) are most active during the waking state. Their activation is deemed to cause a switch in the global brain activity from sleep to wakefulness, while their sustained discharge may contribute to upholding the waking state and enhancing arousal. Similarly, non-cholinergic PPN neurons are responsive to brain state transitions and their activation may influence some of the same targets of cholinergic neurons, suggesting that they operate in coordination. Yet, it is not clear how the discharge of distinct classes of PPN neurons organize during brain states. Here, we monitored the in vivo network activity of PPN neurons in the anesthetized rat across two distinct levels of cortical dynamics and their transitions. We identified a highly structured configuration in PPN network activity during slow-wave activity that was replaced by decorrelated activity during the activated state (AS). During the transition, neurons were predominantly excited (phasically or tonically), but some were inhibited. Identified cholinergic neurons displayed phasic and short latency responses to sensory stimulation, whereas the majority of non-cholinergic showed tonic responses and remained at high discharge rates beyond the state transition. In vitro recordings demonstrate that cholinergic neurons exhibit fast adaptation that prevents them from discharging at high rates over prolonged time periods. Our data shows that PPN neurons have distinct but complementary roles during brain state transitions, where cholinergic neurons provide a fast and transient response to sensory events that drive state transitions, whereas non-cholinergic neurons maintain an elevated firing rate during global activation. PMID:26582977

Learning Temporal Statistics for Sensory Predictions in Aging.

PubMed

Luft, Caroline Di Bernardi; Baker, Rosalind; Goldstone, Aimee; Zhang, Yang; Kourtzi, Zoe

2016-03-01

Predicting future events based on previous knowledge about the environment is critical for successful everyday interactions. Here, we ask which brain regions support our ability to predict the future based on implicit knowledge about the past in young and older age. Combining behavioral and fMRI measurements, we test whether training on structured temporal sequences improves the ability to predict upcoming sensory events; we then compare brain regions involved in learning predictive structures between young and older adults. Our behavioral results demonstrate that exposure to temporal sequences without feedback facilitates the ability of young and older adults to predict the orientation of an upcoming stimulus. Our fMRI results provide evidence for the involvement of corticostriatal regions in learning predictive structures in both young and older learners. In particular, we showed learning-dependent fMRI responses for structured sequences in frontoparietal regions and the striatum (putamen) for young adults. However, for older adults, learning-dependent activations were observed mainly in subcortical (putamen, thalamus) regions but were weaker in frontoparietal regions. Significant correlations of learning-dependent behavioral and fMRI changes in these regions suggest a strong link between brain activations and behavioral improvement rather than general overactivation. Thus, our findings suggest that predicting future events based on knowledge of temporal statistics engages brain regions involved in implicit learning in both young and older adults.

Physical attractiveness and sex as modulatory factors of empathic brain responses to pain

PubMed Central

Jankowiak-Siuda, Kamila; Rymarczyk, Krystyna; Żurawski, Łukasz; Jednoróg, Katarzyna; Marchewka, Artur

2015-01-01

Empathy is a process that comprises affective sharing, imagining, and understanding the emotions and mental states of others. The brain structures involved in empathy for physical pain include the anterior insula (AI), and the anterior cingulate cortex (ACC). High empathy may lead people to undertake pro-social behavior. It is important to understand how this process can be changed, and what factors these empathic responses depend on. Physical attractiveness is a major social and evolutional cue, playing a role in the formation of interpersonal evaluation. The aim of the study was to determine how attractiveness affects the level of empathy both in relation to self-rated behavior and in terms of activation of specific empathy-related brain regions. Twenty-seven subjects (14 female and 13 male) were studied using functional magnetic resonance imaging (fMRI) method while they were watching short video scenes involving physically more and less attractive men and women who exhibited pain responses. In the absence of behavioral effects in compassion ratings, we observed stronger activation in empathic brain structures (ACC; AI) for less attractive men and for attractive women than for attractive men. Evolutionary psychology studies suggest that beauty is valued more highly in females than males, which might lead observers to empathize more strongly with the attractive woman than the men. Attractive mens’ faces are typically associated with enhanced masculine facial characteristics and are considered to possess fewer desirable personality traits compared with feminized faces. This could explain why more empathy was shown to less attractive men. In conclusion, the study showed that the attractiveness and sex of a model are important modulators of empathy for pain. PMID:26441569

Neurobiological Substrates for the Dark Side of Compulsivity in Addiction

PubMed Central

Koob, George F.

2009-01-01

Drug addiction can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Drug addiction impacts multiple motivational mechanisms and can be conceptualized as a disorder that progresses from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The construct of negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of key neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreases in dopamine and opioid peptide function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, increases in anxiety-like responses, and increases in extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of addiction. Other components of brain stress systems in the extended amygdala that interact with CRF and may contribute to the negative motivational state of withdrawal include norepinephrine, dynorphin, and neuropeptide Y. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for a negative emotional state that is responsible for the negative reinforcement driving, at least in part, the compulsivity of addiction. PMID:18725236

Physical attractiveness and sex as modulatory factors of empathic brain responses to pain.

PubMed

Jankowiak-Siuda, Kamila; Rymarczyk, Krystyna; Żurawski, Łukasz; Jednoróg, Katarzyna; Marchewka, Artur

2015-01-01

Empathy is a process that comprises affective sharing, imagining, and understanding the emotions and mental states of others. The brain structures involved in empathy for physical pain include the anterior insula (AI), and the anterior cingulate cortex (ACC). High empathy may lead people to undertake pro-social behavior. It is important to understand how this process can be changed, and what factors these empathic responses depend on. Physical attractiveness is a major social and evolutional cue, playing a role in the formation of interpersonal evaluation. The aim of the study was to determine how attractiveness affects the level of empathy both in relation to self-rated behavior and in terms of activation of specific empathy-related brain regions. Twenty-seven subjects (14 female and 13 male) were studied using functional magnetic resonance imaging (fMRI) method while they were watching short video scenes involving physically more and less attractive men and women who exhibited pain responses. In the absence of behavioral effects in compassion ratings, we observed stronger activation in empathic brain structures (ACC; AI) for less attractive men and for attractive women than for attractive men. Evolutionary psychology studies suggest that beauty is valued more highly in females than males, which might lead observers to empathize more strongly with the attractive woman than the men. Attractive mens' faces are typically associated with enhanced masculine facial characteristics and are considered to possess fewer desirable personality traits compared with feminized faces. This could explain why more empathy was shown to less attractive men. In conclusion, the study showed that the attractiveness and sex of a model are important modulators of empathy for pain.

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

PubMed

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

2015-01-01

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

Developmental Thyroid Hormone Insufficiency Impairs Visual Contrast Sensitivity in Adult Male Offspring.

EPA Science Inventory

Severe thyroid hormone (TH) insufficiency during early development results in alterations in brain structure and function. Many environmental agents produce subtle alterations in TH status, but the dose-response relationships for such effects are unclear. We have previously demon...

Brain-derived neurotrophic factor as a regulator of systemic and brain energy metabolism and cardiovascular health

PubMed Central

Rothman, Sarah M; Griffioen, Kathleen J; Wan, Ruiqian; Mattson, Mark P

2012-01-01

Overweight sedentary individuals are at increased risk for cardiovascular disease, diabetes, and some neurological disorders. Beneficial effects of dietary energy restriction (DER) and exercise on brain structural plasticity and behaviors have been demonstrated in animal models of aging and acute (stroke and trauma) and chronic (Alzheimer's and Parkinson's diseases) neurological disorders. The findings described later, and evolutionary considerations, suggest brain-derived neurotrophic factor (BDNF) plays a critical role in the integration and optimization of behavioral and metabolic responses to environments with limited energy resources and intense competition. In particular, BDNF signaling mediates adaptive responses of the central, autonomic, and peripheral nervous systems from exercise and DER. In the hypothalamus, BDNF inhibits food intake and increases energy expenditure. By promoting synaptic plasticity and neurogenesis in the hippocampus, BDNF mediates exercise- and DER-induced improvements in cognitive function and neuroprotection. DER improves cardiovascular stress adaptation by a mechanism involving enhancement of brainstem cholinergic activity. Collectively, findings reviewed in this paper provide a rationale for targeting BDNF signaling for novel therapeutic interventions in a range of metabolic and neurological disorders. PMID:22548651

Right mesial temporal lobe epilepsy impairs empathy-related brain responses to dynamic fearful faces.

PubMed

Toller, Gianina; Adhimoolam, Babu; Grunwald, Thomas; Huppertz, Hans-Jürgen; Kurthen, Martin; Rankin, Katherine P; Jokeit, Hennric

2015-03-01

Unilateral mesial temporal lobe epilepsy (MTLE) has been associated with reduced amygdala responsiveness to fearful faces. However, the effect of unilateral MTLE on empathy-related brain responses in extra-amygdalar regions has not been investigated. Using functional magnetic resonance imaging, we measured empathy-related brain responses to dynamic fearful faces in 34 patients with unilateral MTLE (18 right sided), in an epilepsy (extra-MTLE; n = 16) and in a healthy control group (n = 30). The primary finding was that right MTLE (RMTLE) was associated with decreased activity predominantly in the right amygdala and also in bilateral periaqueductal gray (PAG) but normal activity in the right anterior insula. The results of the extra-MTLE group demonstrate that these reduced amygdala and PAG responses go beyond the attenuation caused by antiepileptic and antidepressant medication. These findings clearly indicate that RMTLE affects the function of mesial temporal and midbrain structures that mediate basic interoceptive input necessary for the emotional awareness of empathic experiences of fear. Together with the decreased empathic concern found in the RMTLE group, this study provides neurobehavioral evidence that patients with RMTLE are at increased risk for reduced empathy towards others' internal states and sheds new light on the nature of social-cognitive impairments frequently accompanying MTLE.

Structural and functional imaging studies in chronic cannabis users: a systematic review of adolescent and adult findings.

PubMed

Batalla, Albert; Bhattacharyya, Sagnik; Yücel, Murat; Fusar-Poli, Paolo; Crippa, Jose Alexandre; Nogué, Santiago; Torrens, Marta; Pujol, Jesús; Farré, Magí; Martin-Santos, Rocio

2013-01-01

The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure. However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings. Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives.

Structural and Functional Imaging Studies in Chronic Cannabis Users: A Systematic Review of Adolescent and Adult Findings

PubMed Central

Batalla, Albert; Bhattacharyya, Sagnik; Yücel, Murat; Fusar-Poli, Paolo; Crippa, Jose Alexandre; Nogué, Santiago; Torrens, Marta; Pujol, Jesús; Farré, Magí; Martin-Santos, Rocio

2013-01-01

Background The growing concern about cannabis use, the most commonly used illicit drug worldwide, has led to a significant increase in the number of human studies using neuroimaging techniques to determine the effect of cannabis on brain structure and function. We conducted a systematic review to assess the evidence of the impact of chronic cannabis use on brain structure and function in adults and adolescents. Methods Papers published until August 2012 were included from EMBASE, Medline, PubMed and LILACS databases following a comprehensive search strategy and pre-determined set of criteria for article selection. Only neuroimaging studies involving chronic cannabis users with a matched control group were considered. Results One hundred and forty-two studies were identified, of which 43 met the established criteria. Eight studies were in adolescent population. Neuroimaging studies provide evidence of morphological brain alterations in both population groups, particularly in the medial temporal and frontal cortices, as well as the cerebellum. These effects may be related to the amount of cannabis exposure. Functional neuroimaging studies suggest different patterns of resting global and brain activity during the performance of several cognitive tasks both in adolescents and adults, which may indicate compensatory effects in response to chronic cannabis exposure. Limitations However, the results pointed out methodological limitations of the work conducted to date and considerable heterogeneity in the findings. Conclusion Chronic cannabis use may alter brain structure and function in adult and adolescent population. Further studies should consider the use of convergent methodology, prospective large samples involving adolescent to adulthood subjects, and data-sharing initiatives. PMID:23390554

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

PubMed

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

2013-01-01

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

Tau pathology does not affect experience-driven single-neuron and network-wide Arc/Arg3.1 responses.

PubMed

Rudinskiy, Nikita; Hawkes, Jonathan M; Wegmann, Susanne; Kuchibhotla, Kishore V; Muzikansky, Alona; Betensky, Rebecca A; Spires-Jones, Tara L; Hyman, Bradley T

2014-06-10

Intraneuronal neurofibrillary tangles (NFTs) - a characteristic pathological feature of Alzheimer's and several other neurodegenerative diseases - are considered a major target for drug development. Tangle load correlates well with the severity of cognitive symptoms and mouse models of tauopathy are behaviorally impaired. However, there is little evidence that NFTs directly impact physiological properties of host neurons. Here we used a transgenic mouse model of tauopathy to study how advanced tau pathology in different brain regions affects activity-driven expression of immediate-early gene Arc required for experience-dependent consolidation of long-term memories. We demonstrate in vivo that visual cortex neurons with tangles are as likely to express comparable amounts of Arc in response to structured visual stimulation as their neighbors without tangles. Probability of experience-dependent Arc response was not affected by tau tangles in both visual cortex and hippocampal pyramidal neurons as determined postmortem. Moreover, whole brain analysis showed that network-wide activity-driven Arc expression was not affected by tau pathology in any of the brain regions, including brain areas with the highest tangle load. Our findings suggest that intraneuronal NFTs do not affect signaling cascades leading to experience-dependent gene expression required for long-term synaptic plasticity.

A neuroimaging study of emotion-cognition interaction in schizophrenia: the effect of ziprasidone treatment.

PubMed

Stip, Emmanuel; Cherbal, Adel; Luck, David; Zhornitsky, Simon; Bentaleb, Lahcen Ait; Lungu, Ovidiu

2017-04-01

Functional and structural brain changes associated with the cognitive processing of emotional visual stimuli were assessed in schizophrenic patients after 16 weeks of antipsychotic treatment with ziprasidone. Forty-five adults aged 18 to 40 were recruited: 15 schizophrenia patients (DSM-IV criteria) treated with ziprasidone (mean daily dose = 120 mg), 15 patients treated with other antipsychotics, and 15 healthy controls who did not receive any medication. Functional and structural neuroimaging data were acquired at baseline and 16 weeks after treatment initiation. In each session, participants selected stimuli, taken from standardized sets, based on their emotional valence. After ziprasidone treatment, several prefrontal regions, typically involved in cognitive control (anterior cingulate and ventrolateral prefrontal cortices), were significantly activated in patients in response to positive versus negative stimuli. This effect was greater whenever they had to select negative compared to positive stimuli, indicating an asymmetric effect of cognitive treatment of emotionally laden information. No such changes were observed for patients under other antipsychotics. In addition, there was an increase in the brain volume commonly recruited by healthy controls and patients under ziprasidone, in response to cognitive processing of emotional information. The structural analysis showed no significant changes in the density of gray and white matter in ziprasidone-treated patients compared to patients receiving other antipsychotic treatments. Our results suggest that functional changes in brain activity after ziprasidone medication precede structural and clinical manifestations, as markers that the treatment is efficient in restoring the functionality of prefrontal circuits involved in processing emotionally laden information in schizophrenia.

Spectral Variability in the Aged Brain during Fine Motor Control

PubMed Central

Quandt, Fanny; Bönstrup, Marlene; Schulz, Robert; Timmermann, Jan E.; Zimerman, Maximo; Nolte, Guido; Hummel, Friedhelm C.

2016-01-01

Physiological aging is paralleled by a decline of fine motor skills accompanied by structural and functional alterations of the underlying brain network. Here, we aim to investigate age-related changes in the spectral distribution of neuronal oscillations during fine skilled motor function. We employ the concept of spectral entropy in order to describe the flatness and peaked-ness of a frequency spectrum to quantify changes in the spectral distribution of the oscillatory motor response in the aged brain. Electroencephalogram was recorded in elderly (n = 32) and young (n = 34) participants who performed either a cued finger movement or a pinch or a whole hand grip task with their dominant right hand. Whereas young participant showed distinct, well-defined movement-related power decreases in the alpha and upper beta band, elderly participants exhibited a flat broadband, frequency-unspecific power desynchronization. This broadband response was reflected by an increase of spectral entropy over sensorimotor and frontal areas in the aged brain. Neuronal activation patterns differed between motor tasks in the young brain, while the aged brain showed a similar activation pattern in all tasks. Moreover, we found a wider recruitment of the cortical motor network in the aged brain. The present study adds to the understanding of age-related changes of neural coding during skilled motor behavior, revealing a less predictable signal with great variability across frequencies in a wide cortical motor network in the aged brain. The increase in entropy in the aged brain could be a reflection of random noise-like activity or could represent a compensatory mechanism that serves a functional role. PMID:28066231

Cortical Sensitivity to Guitar Note Patterns: EEG Entrainment to Repetition and Key.

PubMed

Bridwell, David A; Leslie, Emily; McCoy, Dakarai Q; Plis, Sergey M; Calhoun, Vince D

2017-01-01

Music is ubiquitous throughout recent human culture, and many individual's have an innate ability to appreciate and understand music. Our appreciation of music likely emerges from the brain's ability to process a series of repeated complex acoustic patterns. In order to understand these processes further, cortical responses were measured to a series of guitar notes presented with a musical pattern or without a pattern. ERP responses to individual notes were measured using a 24 electrode Bluetooth mobile EEG system (Smarting mBrainTrain) while 13 healthy non-musicians listened to structured (i.e., within musical keys and with repetition) or random sequences of guitar notes for 10 min each. We demonstrate an increased amplitude to the ERP that appears ~200 ms to notes presented within the musical sequence. This amplitude difference between random notes and patterned notes likely reflects individual's cortical sensitivity to guitar note patterns. These amplitudes were compared to ERP responses to a rare note embedded within a stream of frequent notes to determine whether the sensitivity to complex musical structure overlaps with the sensitivity to simple irregularities reflected in traditional auditory oddball experiments. Response amplitudes to the negative peak at ~175 ms are statistically correlated with the mismatch negativity (MMN) response measured to a rare note presented among a series of frequent notes (i.e., in a traditional oddball sequence), but responses to the subsequent positive peak at ~200 do not show a statistical relationship with the P300 response. Thus, the sensitivity to musical structure identified to 4 Hz note patterns appears somewhat distinct from the sensitivity to statistical regularities reflected in the traditional "auditory oddball" sequence. Overall, we suggest that this is a promising approach to examine individual's sensitivity to complex acoustic patterns, which may overlap with higher level cognitive processes, including language.

Viral infection, inflammation and schizophrenia

PubMed Central

Kneeland, Rachel E.; Fatemi, S. Hossein

2012-01-01

Schizophrenia is a severe neurodevelopmental disorder with genetic and environmental etiologies. Prenatal viral/bacterial infections and inflammation play major roles in the genesis of schizophrenia. In this review, we describe a viral model of schizophrenia tested in mice whereby the offspring of mice prenatally infected with influenza at E7, E9, E16, and E18 show significant gene, protein, and brain structural abnormalities postnatally. Similarly, we describe data on rodents exposed to bacterial infection or injected with a synthetic viral mimic (PolyI:C) also demonstrating brain structural and behavioral abnormalities. Moreover, human serologic data has been indispensible in supporting the viral theory of schizophrenia. Individuals born seropositive for bacterial and viral agents are at a significantly elevated risk of developing schizophrenia. While the specific mechanisms of prenatal viral/bacterial infections and brain disorder are unclear, recent findings suggest that the maternal inflammatory response may be associated with fetal brain injury. Preventive and therapeutic treatment options are also proposed. This review presents data related to epidemiology, human serology, and experimental animal models which support the viral model of schizophrenia. PMID:22349576

Brain’s DNA Repair Response to Neurotoxicants

DTIC Science & Technology

2005-07-01

it is possible that OTA exposure may impact on this ability of this structure to maintain its functional integrity over time. Indeed it is known...Gordon et al., 2004). In light of the critical role played by hippocampus in cognitive function, and the importance of neurogenesis in this structure ...uncompetitive inhibitorof both succinate-cytochrome c reductase and succinate dehydrogenase while sparing cytochrome oxidase and NADH dehydrogenase

Quantum probability, choice in large worlds, and the statistical structure of reality.

PubMed

Ross, Don; Ladyman, James

2013-06-01

Classical probability models of incentive response are inadequate in "large worlds," where the dimensions of relative risk and the dimensions of similarity in outcome comparisons typically differ. Quantum probability models for choice in large worlds may be motivated pragmatically - there is no third theory - or metaphysically: statistical processing in the brain adapts to the true scale-relative structure of the universe.

Lateralized sex differences in stress-induced dopamine release in the rat.

PubMed

Sullivan, Ron M; Dufresne, Marc M; Waldron, Jay

2009-02-18

This study examined the possibility that hemispheric differences in stress-induced brain activation vary as a function of sex. Using in-vivo voltammetry, increases in extracellular dopamine release in response to predator odour and tail pinch stress were recorded bilaterally and simultaneously in either the infralimbic cortex or basolateral amygdala. In both stress-sensitive brain regions, significant sex x hemisphere interactions were observed, with males and females showing greater dopamine activation in right-brain and left-brain structures, respectively. Cortical asymmetries in dopamine release also showed sex-specific correlations with stress-induced neuroendocrine activation. Given the intriguing human parallels, we suggest that differential cerebral lateralization may be highly relevant to the disproportionately high incidence of stress-related disorders such as depression and anxiety seen in women.

Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex.

PubMed

Oliva, Carlos; Soldano, Alessia; Mora, Natalia; De Geest, Natalie; Claeys, Annelies; Erfurth, Maria-Luise; Sierralta, Jimena; Ramaekers, Ariane; Dascenco, Dan; Ejsmont, Radoslaw K; Schmucker, Dietmar; Sanchez-Soriano, Natalia; Hassan, Bassem A

2016-10-24

The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Movement maintains forebrain neurogenesis via peripheral neural feedback in larval zebrafish

PubMed Central

Hall, Zachary Jonas

2018-01-01

The postembryonic brain exhibits experience-dependent development, in which sensory experience guides normal brain growth. This neuroplasticity is thought to occur primarily through structural and functional changes in pre-existing neurons. Whether neurogenesis also mediates the effects of experience on brain growth is unclear. Here, we characterized the importance of motor experience on postembryonic neurogenesis in larval zebrafish. We found that movement maintains an expanded pool of forebrain neural precursors by promoting progenitor self-renewal over the production of neurons. Physical cues associated with swimming (bodily movement) increase neurogenesis and these cues appear to be conveyed by dorsal root ganglia (DRG) in the zebrafish body: DRG-deficient larvae exhibit attenuated neurogenic responses to movement and targeted photoactivation of DRG in immobilized larvae expands the pallial pool of proliferative cells. Our results demonstrate the importance of movement in neurogenic brain growth and reveal a fundamental sensorimotor association that may couple early motor and brain development. PMID:29528285

Emotional self-reference: brain structures involved in the processing of words describing one's own emotions.

PubMed

Herbert, Cornelia; Herbert, Beate M; Pauli, Paul

2011-08-01

The present functional magnetic resonance imaging study investigated the role of emotion-related (e.g., amygdala) and self-related brain structures (MPFC in particular) in the processing of emotional words varying in stimulus reference. Healthy subjects (N=22) were presented with emotional (pleasant or unpleasant) or neutral words in three different conditions: (1) self (e.g., my fear), (2) other (e.g., his fear) and (3) no reference (e.g., the fear). Processing of unpleasant words was associated with increased amygdala and also insula activation across all conditions. Pleasant stimuli were specifically associated with increased activation of amygdala and insula when related to the self (vs. other and no reference). Activity in the MPFC (vMPFC in particular) and anterior cingulate cortex (ACC) was preferentially increased during processing of self-related emotional words (vs. other and no reference). These results demonstrate that amygdala activation in response to emotional stimuli is modulated by stimulus reference and that brain structures implicated in emotional and self-related processing might be important for the subjective experience of one's own emotions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Baseline Gray- and White Matter Volume Predict Successful Weight Loss in the Elderly

PubMed Central

Mokhtari, Fatemeh; Paolini, Brielle M.; Burdette, Jonathan H.; Marsh, Anthony P.; Rejeski, W. Jack; Laurienti, Paul J.

2016-01-01

Objective The purpose of this study is to investigate if structural brain phenotypes can be used to predict weight loss success following behavioral interventions in older adults that are overweight or obese and have cardiometabolic dysfunction. Methods A support vector machine (SVM) with a repeated random subsampling validation approach was used to classify participants into the upper and lower halves of the weight loss distribution following 18 months of a weight loss intervention. Predictions were based on baseline brain gray matter (GM) and white matter (WM) volume from 52 individuals that completed the intervention and a magnetic resonance imaging session. Results The SVM resulted in an average classification accuracy of 72.62 % based on GM and WM volume. A receiver operating characteristic analysis indicated that classification performance was robust based on an area under the curve of 0.82. Conclusions Our findings suggest that baseline brain structure is able to predict weight loss success following 18 months of treatment. The identification of brain structure as a predictor of successful weight loss is an innovative approach to identifying phenotypes for responsiveness to intensive lifestyle interventions. This phenotype could prove useful in future research focusing on the tailoring of treatment for weight loss. PMID:27804273

Dynamics of brain activity in motor and frontal cortical areas during music listening: a magnetoencephalographic study.

PubMed

Popescu, Mihai; Otsuka, Asuka; Ioannides, Andreas A

2004-04-01

There are formidable problems in studying how 'real' music engages the brain over wide ranges of temporal scales extending from milliseconds to a lifetime. In this work, we recorded the magnetoencephalographic signal while subjects listened to music as it unfolded over long periods of time (seconds), and we developed and applied methods to correlate the time course of the regional brain activations with the dynamic aspects of the musical sound. We showed that frontal areas generally respond with slow time constants to the music, reflecting their more integrative mode; motor-related areas showed transient-mode responses to fine temporal scale structures of the sound. The study combined novel analysis techniques designed to capture and quantify fine temporal sequencing from the authentic musical piece (characterized by a clearly defined rhythm and melodic structure) with the extraction of relevant features from the dynamics of the regional brain activations. The results demonstrated that activity in motor-related structures, specifically in lateral premotor areas, supplementary motor areas, and somatomotor areas, correlated with measures of rhythmicity derived from the music. These correlations showed distinct laterality depending on how the musical performance deviated from the strict tempo of the music score, that is, depending on the musical expression.

Structural and functional bases of inhibited temperament.

PubMed

Clauss, Jacqueline A; Seay, April L; VanDerKlok, Ross M; Avery, Suzanne N; Cao, Aize; Cowan, Ronald L; Benningfield, Margaret M; Blackford, Jennifer Urbano

2014-12-01

Children born with an inhibited temperament are at heightened risk for developing anxiety, depression and substance use. Inhibited temperament is believed to have a biological basis; however, little is known about the structural brain basis of this vulnerability trait. Structural MRI scans were obtained from 84 (44 inhibited, 40 uninhibited) young adults. Given previous findings of amygdala hyperactivity in inhibited individuals, groups were compared on three measures of amygdala structure. To identify novel substrates of inhibited temperament, a whole brain analysis was performed. Functional activation and connectivity were examined across both groups. Inhibited adults had larger amygdala and caudate volume and larger volume predicted greater activation to neutral faces. In addition, larger amygdala volume predicted greater connectivity with subcortical and higher order visual structures. Larger caudate volume predicted greater connectivity with the basal ganglia, and less connectivity with primary visual and auditory cortex. We propose that larger volume in these salience detection regions may result in increased activation and enhanced connectivity in response to social stimuli. Given the strong link between inhibited temperament and risk for psychiatric illness, novel therapeutics that target these brain regions and related neural circuits have the potential to reduce rates of illness in vulnerable individuals. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Serum S100B Protein is Specifically Related to White Matter Changes in Schizophrenia

PubMed Central

Milleit, Berko; Smesny, Stefan; Rothermundt, Matthias; Preul, Christoph; Schroeter, Matthias L.; von Eiff, Christof; Ponath, Gerald; Milleit, Christine; Sauer, Heinrich; Gaser, Christian

2016-01-01

Background: Schizophrenia can be conceptualized as a form of dysconnectivity between brain regions.To investigate the neurobiological foundation of dysconnectivity, one approach is to analyze white matter structures, such as the pathology of fiber tracks. S100B is considered a marker protein for glial cells, in particular oligodendrocytes and astroglia, that passes the blood brain barrier and is detectable in peripheral blood. Earlier Studies have consistently reported increased S100B levels in schizophrenia. In this study, we aim to investigate associations between S100B and structural white matter abnormalities. Methods: We analyzed data of 17 unmedicated schizophrenic patients (first and recurrent episode) and 22 controls. We used voxel based morphometry (VBM) to detect group differences of white matter structures as obtained from T1-weighted MR-images and considered S100B serum levels as a regressor in an age-corrected interaction analysis. Results: S100B was increased in both patient subgroups. Using VBM, we found clusters indicating significant differences of the association between S100B concentration and white matter. Involved anatomical structures are the posterior cingulate bundle and temporal white matter structures assigned to the superior longitudinal fasciculus. Conclusions: S100B-associated alterations of white matter are shown to be existent already at time of first manifestation of psychosis and are distinct from findings in recurrent episode patients. This suggests involvement of S100B in an ongoing and dynamic process associated with structural brain changes in schizophrenia. However, it remains elusive whether increased S100B serum concentrations in psychotic patients represent a protective response to a continuous pathogenic process or if elevated S100B levels are actively involved in promoting structural brain damage. PMID:27013967

Three Types of Cortical L5 Neurons that Differ in Brain-Wide Connectivity and Function

PubMed Central

Kim, Euiseok J.; Juavinett, Ashley L.; Kyubwa, Espoir M.; Jacobs, Matthew W.; Callaway, Edward M.

2015-01-01

SUMMARY Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. PMID:26671462

Three Types of Cortical Layer 5 Neurons That Differ in Brain-wide Connectivity and Function.

PubMed

Kim, Euiseok J; Juavinett, Ashley L; Kyubwa, Espoir M; Jacobs, Matthew W; Callaway, Edward M

2015-12-16

Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology, and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception. Copyright © 2015 Elsevier Inc. All rights reserved.

The Neuroendocrinology of Thirst and Salt Appetite: Visceral Sensory Signals and Mechanisms of Central Integration

NASA Technical Reports Server (NTRS)

Johnson, Alan Kim; Thunhorst, Robert L.

1997-01-01

This review examines recent advances in the study of the behavioral responses to deficits of body water and body sodium that in humans are accompanied by the sensations of thirst and salt appetite. Thirst and salt appetite are satisfied by ingesting water and salty substances. These behavioral responses to losses of body fluids, together with reflex endocrine and neural responses, are critical for reestablishing homeostasis. Like their endocrine and neural counterparts, these behaviors are under the control of both excitatory and inhibitory influences arising from changes in osmolality, endocrine factors such as angiotensin and aldosterone, and neural signals from low and high pressure baroreceptors. The excitatory and inhibitory influences reaching the brain require the integrative capacity of a neural network which includes the structures of the lamina terminalis, the amygdala, the perifornical area, and the paraventricular nucleus in the forebrain, and the lateral parabrachial nucleus (LPBN), the nucleus tractus solitarius (NTS), and the area postrema in the hindbrain. These regions are discussed in terms of their roles in receiving afferent sensory input and in processing information related to hydromineral balance. Osmoreceptors controlling thirst are located in systemic Viscera and in central structures that lack the blood-brain barrier. Angiotensin and aldosterone act on and through structures of the lamina terminalis and the amygdala to stimulate thirst and sodium appetite under conditions of hypovolemia. The NTS and LPBN receive neural signals from baroreceptors and are responsible for inhibiting the ingestion of fluids under conditions of increased volume and pressure and for stimulating thirst under conditions of bypovolemia and hypotension. The interplay of multiple facilitory influences within the brain may take the form of interactions between descending angiotensinergic systems originating in the forebrain and ascending adrenergic systems emanating from the hindbrain. Oxytocin and serotonin are additional candidate neuro- chemicals with postulated inhibitory central actions and with essential roles in the overall integration of sensory input within the neural network devoted to maintaining hydromineral balance.

Effect of brain shift on the creation of functional atlases for deep brain stimulation surgery

PubMed Central

Pallavaram, Srivatsan; Remple, Michael S.; Neimat, Joseph S.; Kao, Chris; Konrad, Peter E.; D’Haese, Pierre-François

2011-01-01

Purpose In the recent past many groups have tried to build functional atlases of the deep brain using intra-operatively acquired information such as stimulation responses or micro-electrode recordings. An underlying assumption in building such atlases is that anatomical structures do not move between pre-operative imaging and intra-operative recording. In this study, we present evidences that this assumption is not valid. We quantify the effect of brain shift between pre-operative imaging and intra-operative recording on the creation of functional atlases using intra-operative somatotopy recordings and stimulation response data. Methods A total of 73 somatotopy points from 24 bilateral subthalamic nucleus (STN) implantations and 52 eye deviation stimulation response points from 17 bilateral STN implantations were used. These points were spatially normalized on a magnetic resonance imaging (MRI) atlas using a fully automatic non-rigid registration algorithm. Each implantation was categorized as having low, medium or large brain shift based on the amount of pneumocephalus visible on post-operative CT. The locations of somatotopy clusters and stimulation maps were analyzed for each category. Results The centroid of the large brain shift cluster of the somatotopy data (posterior, lateral, inferior: 3.06, 11.27, 5.36 mm) was found posterior, medial and inferior to that of the medium cluster (2.90, 13.57, 4.53 mm) which was posterior, medial and inferior to that of the low shift cluster (1.94, 13.92, 3.20 mm). The coordinates are referenced with respect to the mid-commissural point. Euclidean distances between the centroids were 1.68, 2.44 and 3.59 mm, respectively for low-medium, medium-large and low-large shift clusters. We found similar trends for the positions of the stimulation maps. The Euclidian distance between the highest probability locations on the low and medium-large shift maps was 4.06 mm. Conclusion The effect of brain shift in deep brain stimulation (DBS) surgery has been demonstrated using intra-operative somatotopy recordings as well as stimulation response data. The results not only indicate that considerable brain shift happens before micro-electrode recordings in DBS but also that brain shift affects the creation of accurate functional atlases. Therefore, care must be taken when building and using such atlases of intra-operative data and also when using intra-operative data to validate anatomical atlases. PMID:20033503

Plasticity of brain wave network interactions and evolution across physiologic states

PubMed Central

Liu, Kang K. L.; Bartsch, Ronny P.; Lin, Aijing; Mantegna, Rosario N.; Ivanov, Plamen Ch.

2015-01-01

Neural plasticity transcends a range of spatio-temporal scales and serves as the basis of various brain activities and physiologic functions. At the microscopic level, it enables the emergence of brain waves with complex temporal dynamics. At the macroscopic level, presence and dominance of specific brain waves is associated with important brain functions. The role of neural plasticity at different levels in generating distinct brain rhythms and how brain rhythms communicate with each other across brain areas to generate physiologic states and functions remains not understood. Here we perform an empirical exploration of neural plasticity at the level of brain wave network interactions representing dynamical communications within and between different brain areas in the frequency domain. We introduce the concept of time delay stability (TDS) to quantify coordinated bursts in the activity of brain waves, and we employ a system-wide Network Physiology integrative approach to probe the network of coordinated brain wave activations and its evolution across physiologic states. We find an association between network structure and physiologic states. We uncover a hierarchical reorganization in the brain wave networks in response to changes in physiologic state, indicating new aspects of neural plasticity at the integrated level. Globally, we find that the entire brain network undergoes a pronounced transition from low connectivity in Deep Sleep and REM to high connectivity in Light Sleep and Wake. In contrast, we find that locally, different brain areas exhibit different network dynamics of brain wave interactions to achieve differentiation in function during different sleep stages. Moreover, our analyses indicate that plasticity also emerges in frequency-specific networks, which represent interactions across brain locations mediated through a specific frequency band. Comparing frequency-specific networks within the same physiologic state we find very different degree of network connectivity and link strength, while at the same time each frequency-specific network is characterized by a different signature pattern of sleep-stage stratification, reflecting a remarkable flexibility in response to change in physiologic state. These new aspects of neural plasticity demonstrate that in addition to dominant brain waves, the network of brain wave interactions is a previously unrecognized hallmark of physiologic state and function. PMID:26578891

ConnectViz: Accelerated Approach for Brain Structural Connectivity Using Delaunay Triangulation.

PubMed

Adeshina, A M; Hashim, R

2016-03-01

Stroke is a cardiovascular disease with high mortality and long-term disability in the world. Normal functioning of the brain is dependent on the adequate supply of oxygen and nutrients to the brain complex network through the blood vessels. Stroke, occasionally a hemorrhagic stroke, ischemia or other blood vessel dysfunctions can affect patients during a cerebrovascular incident. Structurally, the left and the right carotid arteries, and the right and the left vertebral arteries are responsible for supplying blood to the brain, scalp and the face. However, a number of impairment in the function of the frontal lobes may occur as a result of any decrease in the flow of the blood through one of the internal carotid arteries. Such impairment commonly results in numbness, weakness or paralysis. Recently, the concepts of brain's wiring representation, the connectome, was introduced. However, construction and visualization of such brain network requires tremendous computation. Consequently, previously proposed approaches have been identified with common problems of high memory consumption and slow execution. Furthermore, interactivity in the previously proposed frameworks for brain network is also an outstanding issue. This study proposes an accelerated approach for brain connectomic visualization based on graph theory paradigm using compute unified device architecture, extending the previously proposed SurLens Visualization and computer aided hepatocellular carcinoma frameworks. The accelerated brain structural connectivity framework was evaluated with stripped brain datasets from the Department of Surgery, University of North Carolina, Chapel Hill, USA. Significantly, our proposed framework is able to generate and extract points and edges of datasets, displays nodes and edges in the datasets in form of a network and clearly maps data volume to the corresponding brain surface. Moreover, with the framework, surfaces of the dataset were simultaneously displayed with the nodes and the edges. The framework is very efficient in providing greater interactivity as a way of representing the nodes and the edges intuitively, all achieved at a considerably interactive speed for instantaneous mapping of the datasets' features. Uniquely, the connectomic algorithm performed remarkably fast with normal hardware requirement specifications.

ConnectViz: Accelerated approach for brain structural connectivity using Delaunay triangulation.

PubMed

Adeshina, A M; Hashim, R

2015-02-06

Stroke is a cardiovascular disease with high mortality and long-term disability in the world. Normal functioning of the brain is dependent on the adequate supply of oxygen and nutrients to the brain complex network through the blood vessels. Stroke, occasionally a hemorrhagic stroke, ischemia or other blood vessel dysfunctions can affect patients during a cerebrovascular incident. Structurally, the left and the right carotid arteries, and the right and the left vertebral arteries are responsible for supplying blood to the brain, scalp and the face. However, a number of impairment in the function of the frontal lobes may occur as a result of any decrease in the flow of the blood through one of the internal carotid arteries. Such impairment commonly results in numbness, weakness or paralysis. Recently, the concepts of brain's wiring representation, the connectome, was introduced. However, construction and visualization of such brain network requires tremendous computation. Consequently, previously proposed approaches have been identified with common problems of high memory consumption and slow execution. Furthermore, interactivity in the previously proposed frameworks for brain network is also an outstanding issue. This study proposes an accelerated approach for brain connectomic visualization based on graph theory paradigm using Compute Unified Device Architecture (CUDA), extending the previously proposed SurLens Visualization and Computer Aided Hepatocellular Carcinoma (CAHECA) frameworks. The accelerated brain structural connectivity framework was evaluated with stripped brain datasets from the Department of Surgery, University of North Carolina, Chapel Hill, United States. Significantly, our proposed framework is able to generates and extracts points and edges of datasets, displays nodes and edges in the datasets in form of a network and clearly maps data volume to the corresponding brain surface. Moreover, with the framework, surfaces of the dataset were simultaneously displayed with the nodes and the edges. The framework is very efficient in providing greater interactivity as a way of representing the nodes and the edges intuitively, all achieved at a considerably interactive speed for instantaneous mapping of the datasets' features. Uniquely, the connectomic algorithm performed remarkably fast with normal hardware requirement specifications.

Neuronal Circuitry Mechanisms Regulating Adult Mammalian Neurogenesis

PubMed Central

Song, Juan; Olsen, Reid H.J.; Sun, Jiaqi; Ming, Guo-li; Song, Hongjun

2017-01-01

The adult mammalian brain is a dynamic structure, capable of remodeling in response to various physiological and pathological stimuli. One dramatic example of brain plasticity is the birth and subsequent integration of newborn neurons into the existing circuitry. This process, termed adult neurogenesis, recapitulates neural developmental events in two specialized adult brain regions: the lateral ventricles of the forebrain. Recent studies have begun to delineate how the existing neuronal circuits influence the dynamic process of adult neurogenesis, from activation of quiescent neural stem cells (NSCs) to the integration and survival of newborn neurons. Here, we review recent progress toward understanding the circuit-based regulation of adult neurogenesis in the hippocampus and olfactory bulb. PMID:27143698

Integration of white matter network is associated with interindividual differences in psychologically mediated placebo response in migraine patients.

PubMed

Liu, Jixin; Ma, Shaohui; Mu, Junya; Chen, Tao; Xu, Qing; Dun, Wanghuan; Tian, Jie; Zhang, Ming

2017-10-01

Individual differences of brain changes of neural communication and integration in the modular architecture of the human brain network exist for the repeated migraine attack and physical or psychological stressors. However, whether the interindividual variability in the migraine brain connectome predicts placebo response to placebo treatment is still unclear. Using DTI and graph theory approaches, we systematically investigated the topological organization of white matter networks in 71 patients with migraine without aura (MO) and 50 matched healthy controls at three levels: global network measure, nodal efficiency, and nodal intramodule/intermodule efficiency. All patients participated in an 8-week sham acupuncture treatment to induce analgesia. In our results, 30% (n = 21) of patients had 50% change in migraine days from baseline after placebo treatment. At baseline, abnormal increased network integration was found in MO patients as compared with the HC group, and the increased global efficiency before starting clinical treatment was associated with their following placebo response. For nodal efficiency, significantly increased within-subnetwork nodal efficiency and intersubnetwork connectivity of the hippocampus and middle frontal gyrus in patients' white matter network were correlated with the responses of follow-up placebo treatment. Our findings suggested that the trait-like individual differences in pain-related maladaptive stress interfered with and diminished the capacity of chronic pain modulation differently, and the placebo response for treatment could be predicted from a prior white matter network modular structure in migraineurs. Hum Brain Mapp 38:5250-5259, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Linking EEG signals, brain functions and mental operations: Advantages of the Laplacian transformation.

PubMed

Vidal, Franck; Burle, Boris; Spieser, Laure; Carbonnell, Laurence; Meckler, Cédric; Casini, Laurence; Hasbroucq, Thierry

2015-09-01

Electroencephalography (EEG) is a very popular technique for investigating brain functions and/or mental processes. To this aim, EEG activities must be interpreted in terms of brain and/or mental processes. EEG signals being a direct manifestation of neuronal activity it is often assumed that such interpretations are quite obvious or, at least, straightforward. However, they often rely on (explicit or even implicit) assumptions regarding the structures supposed to generate the EEG activities of interest. For these assumptions to be used appropriately, reliable links between EEG activities and the underlying brain structures must be established. Because of volume conduction effects and the mixture of activities they induce, these links are difficult to establish with scalp potential recordings. We present different examples showing how the Laplacian transformation, acting as an efficient source separation method, allowed to establish more reliable links between EEG activities and brain generators and, ultimately, with mental operations. The nature of those links depends on the depth of inferences that can vary from weak to strong. Along this continuum, we show that 1) while the effects of experimental manipulation can appear widely distributed with scalp potentials, Laplacian transformation allows to reveal several generators contributing (in different manners) to these modulations, 2) amplitude variations within the same set of generators can generate spurious differences in scalp potential topographies, often interpreted as reflecting different source configurations. In such a case, Laplacian transformation provides much more similar topographies, evidencing the same generator(s) set, and 3) using the LRP as an index of response activation most often produces ambiguous results, Laplacian-transformed response-locked ERPs obtained over motor areas allow resolving these ambiguities. Copyright © 2015 Elsevier B.V. All rights reserved.

Negative correlation of cortical thickness with the severity and duration of abdominal pain in Asian women with irritable bowel syndrome.

PubMed

Chua, Chian Sem; Bai, Chyi-Huey; Shiao, Chen-Yu; Hsu, Chien-Yeh; Cheng, Chiao-Wen; Yang, Kuo-Ching; Chiu, Hung-Wen; Hsu, Jung-Lung

2017-01-01

Irritable bowel syndrome (IBS) manifests as chronic abdominal pain. One pathophysiological theory states that the brain-gut axis is responsible for pain control in the intestine. Although several studies have discussed the structural changes in the brain of IBS patients, most of these studies have been conducted in Western populations. Different cultures and sexes experience different pain sensations and have different pain responses. Accordingly, we aimed to identify the specific changes in the cortical thickness of Asian women with IBS and to compare these data to those of non-Asian women with IBS. Thirty Asian female IBS patients (IBS group) and 39 healthy individuals (control group) were included in this study. Brain structural magnetic resonance imaging was performed. We used FreeSurfer to analyze the differences in the cortical thickness and their correlations with patient characteristics. The left cuneus, left rostral middle frontal cortex, left supramarginal cortex, right caudal anterior cingulate cortex, and bilateral insula exhibited cortical thinning in the IBS group compared with those in the controls. Furthermore, the brain cortical thickness correlated negatively the severity as well as duration of abdominal pain. Some of our findings differ from those of Western studies. In our study, all of the significant brain regions in the IBS group exhibited cortical thinning compared with those in the controls. The differences in cortical thickness between the IBS patients and controls may provide useful information to facilitate regulating abdominal pain in IBS patients. These findings offer insights into the association of different cultures and sexes with differences in cortical thinning in patients with IBS.

Markov models for fMRI correlation structure: Is brain functional connectivity small world, or decomposable into networks?

PubMed

Varoquaux, G; Gramfort, A; Poline, J B; Thirion, B

2012-01-01

Correlations in the signal observed via functional Magnetic Resonance Imaging (fMRI), are expected to reveal the interactions in the underlying neural populations through hemodynamic response. In particular, they highlight distributed set of mutually correlated regions that correspond to brain networks related to different cognitive functions. Yet graph-theoretical studies of neural connections give a different picture: that of a highly integrated system with small-world properties: local clustering but with short pathways across the complete structure. We examine the conditional independence properties of the fMRI signal, i.e. its Markov structure, to find realistic assumptions on the connectivity structure that are required to explain the observed functional connectivity. In particular we seek a decomposition of the Markov structure into segregated functional networks using decomposable graphs: a set of strongly-connected and partially overlapping cliques. We introduce a new method to efficiently extract such cliques on a large, strongly-connected graph. We compare methods learning different graph structures from functional connectivity by testing the goodness of fit of the model they learn on new data. We find that summarizing the structure as strongly-connected networks can give a good description only for very large and overlapping networks. These results highlight that Markov models are good tools to identify the structure of brain connectivity from fMRI signals, but for this purpose they must reflect the small-world properties of the underlying neural systems. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed

Jirakittayakorn, Nantawachara; Wongsawat, Yodchanan

2015-01-01

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

Tissue-like Neural Probes for Understanding and Modulating the Brain.

PubMed

Hong, Guosong; Viveros, Robert D; Zwang, Theodore J; Yang, Xiao; Lieber, Charles M

2018-03-19

Electrophysiology tools have contributed substantially to understanding brain function, yet the capabilities of conventional electrophysiology probes have remained limited in key ways because of large structural and mechanical mismatches with respect to neural tissue. In this Perspective, we discuss how the general goal of probe design in biochemistry, that the probe or label have a minimal impact on the properties and function of the system being studied, can be realized by minimizing structural, mechanical, and topological differences between neural probes and brain tissue, thus leading to a new paradigm of tissue-like mesh electronics. The unique properties and capabilities of the tissue-like mesh electronics as well as future opportunities are summarized. First, we discuss the design of an ultraflexible and open mesh structure of electronics that is tissue-like and can be delivered in the brain via minimally invasive syringe injection like molecular and macromolecular pharmaceuticals. Second, we describe the unprecedented tissue healing without chronic immune response that leads to seamless three-dimensional integration with a natural distribution of neurons and other key cells through these tissue-like probes. These unique characteristics lead to unmatched stable long-term, multiplexed mapping and modulation of neural circuits at the single-neuron level on a year time scale. Last, we offer insights on several exciting future directions for the tissue-like electronics paradigm that capitalize on their unique properties to explore biochemical interactions and signaling in a "natural" brain environment.

Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor.

PubMed

Brown, Jacquelyn A; Pensabene, Virginia; Markov, Dmitry A; Allwardt, Vanessa; Neely, M Diana; Shi, Mingjian; Britt, Clayton M; Hoilett, Orlando S; Yang, Qing; Brewer, Bryson M; Samson, Philip C; McCawley, Lisa J; May, James M; Webb, Donna J; Li, Deyu; Bowman, Aaron B; Reiserer, Ronald S; Wikswo, John P

2015-09-01

The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier.

Spatial Memory in the Morris Water Maze and Activation of Cyclic AMP Response Element-Binding (CREB) Protein within the Mouse Hippocampus

ERIC Educational Resources Information Center

Porte, Yves; Buhot, Marie Christine; Mons, Nicole E.

2008-01-01

We investigated the spatio-temporal dynamics of learning-induced cAMP response element-binding protein activation/phosphorylation (pCREB) in mice trained in a spatial reference memory task in the water maze. Using immunohistochemistry, we examined pCREB immunoreactivity (pCREB-ir) in hippocampal CA1 and CA3 and related brain structures. During the…

Entrepreneurial and parental love—are they the same?

PubMed Central

Lahti, Tom; Hytönen, Kaisa; Jääskeläinen, Iiro P.

2017-01-01

Abstract Here we tested the hypothesis that entrepreneurs' emotional experience and brain responses toward their own firm resemble those of parents toward their own children. Using fMRI, we measured the brain activity while male entrepreneurs viewed pictures of their own and of a familiar firm, and while fathers viewed pictures of their own and of a familiar child. The entrepreneurs who self‐rated as being very closely attached with their venture showed a similar suppression of activity in the posterior cingulate cortex, temporoparietal junction, and dorsomedial prefrontal cortex as fathers during viewing pictures of their own children versus familiar children. In addition, individual differences in the confidence trait influenced the neural encoding of both paternal and entrepreneurial processing. For underconfident fathers, a picture of one's own child was associated with stronger activation and for overconfident fathers with weaker activation in the amygdala and in caudate nucleus, a brain structure associated with processing of rewards. Similar association with activation, yet more widespread in the emotional processing network, was observed in entrepreneurs suggesting a similar neural basis for increased sensitivity to threats and potential risks concerning one's venture and child. In conclusion, both entrepreneurial and parental love seem to be supported by brain structures associated with reward and emotional processing as well as social understanding. Hum Brain Mapp 38:2923–2938, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:28295978

Entrepreneurial and parental love-are they the same?

PubMed

Halko, Marja-Liisa; Lahti, Tom; Hytönen, Kaisa; Jääskeläinen, Iiro P

2017-06-01

Here we tested the hypothesis that entrepreneurs' emotional experience and brain responses toward their own firm resemble those of parents toward their own children. Using fMRI, we measured the brain activity while male entrepreneurs viewed pictures of their own and of a familiar firm, and while fathers viewed pictures of their own and of a familiar child. The entrepreneurs who self-rated as being very closely attached with their venture showed a similar suppression of activity in the posterior cingulate cortex, temporoparietal junction, and dorsomedial prefrontal cortex as fathers during viewing pictures of their own children versus familiar children. In addition, individual differences in the confidence trait influenced the neural encoding of both paternal and entrepreneurial processing. For underconfident fathers, a picture of one's own child was associated with stronger activation and for overconfident fathers with weaker activation in the amygdala and in caudate nucleus, a brain structure associated with processing of rewards. Similar association with activation, yet more widespread in the emotional processing network, was observed in entrepreneurs suggesting a similar neural basis for increased sensitivity to threats and potential risks concerning one's venture and child. In conclusion, both entrepreneurial and parental love seem to be supported by brain structures associated with reward and emotional processing as well as social understanding. Hum Brain Mapp 38:2923-2938, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Sparing functional anatomical structures during intensity-modulated radiotherapy: an old problem, a new solution.

PubMed

Tan, Wenyong; Han, Guang; Wei, Shaozhong; Hu, Desheng

2014-08-01

During intensity-modulated radiotherapy, an organ is usually assumed to be functionally homogeneous and, generally, its anatomical and spatial heterogeneity with respect to radiation response are not taken into consideration. However, advances in imaging and radiation techniques as well as an improved understanding of the radiobiological response of organs have raised the possibility of sparing the critical functional structures within various organs at risk during intensity-modulated radiotherapy. Here, we discuss these structures, which include the critical brain structure, or neural nuclei, and the nerve fiber tracts in the CNS, head and neck structures related to radiation-induced salivary and swallowing dysfunction, and functional structures in the heart and lung. We suggest that these structures can be used as potential surrogate organs at risk in order to minimize their radiation dose and/or irradiated volume without compromising the dose coverage of the target volume during radiation treatment.

Neural reactivity to visual food stimuli is reduced in some areas of the brain during evening hours compared to morning hours: an fMRI study in women.

PubMed

Masterson, Travis D; Kirwan, C Brock; Davidson, Lance E; LeCheminant, James D

2016-03-01

The extent that neural responsiveness to visual food stimuli is influenced by time of day is not well examined. Using a crossover design, 15 healthy women were scanned using fMRI while presented with low- and high-energy pictures of food, once in the morning (6:30-8:30 am) and once in the evening (5:00-7:00 pm). Diets were identical on both days of the fMRI scans and were verified using weighed food records. Visual analog scales were used to record subjective perception of hunger and preoccupation with food prior to each fMRI scan. Six areas of the brain showed lower activation in the evening to both high- and low-energy foods, including structures in reward pathways (P < 0.05). Nine brain regions showed significantly higher activation for high-energy foods compared to low-energy foods (P < 0.05). High-energy food stimuli tended to produce greater fMRI responses than low-energy food stimuli in specific areas of the brain, regardless of time of day. However, evening scans showed a lower response to both low- and high-energy food pictures in some areas of the brain. Subjectively, participants reported no difference in hunger by time of day (F = 1.84, P = 0.19), but reported they could eat more (F = 4.83, P = 0.04) and were more preoccupied with thoughts of food (F = 5.51, P = 0.03) in the evening compared to the morning. These data underscore the role that time of day may have on neural responses to food stimuli. These results may also have clinical implications for fMRI measurement in order to prevent a time of day bias.

fMRI of pain studies using laser-induced heat on skin with and without the loved one near the subject - a pilot study on 'love hurts'

NASA Astrophysics Data System (ADS)

Sofina, T.; Kamil, W. A.; Ahmad, A. H.

2014-11-01

The aims of this study are to image and investigate the areas of brain response to laser-induced heat pain, to analyse for any difference in the brain response when a subject is alone and when her loved one is present next to the MRI gantry. Pain stimuli was delivered using Th-YAG laser to four female subjects. Blood-Oxygenation-Level-Dependent (BOLD) fMRI experiment was performed using blocked design paradigm with five blocks of painful (P) stimuli and five blocks of non-painful (NP) stimuli arranged in pseudorandom order with an 18 seconds rest (R) between each stimulation phase. Brain images were obtained from 3T Philips Achieva MRI scanner using 32-channel SENSE head coil. A T1-weighted image (TR/TE/slice/FOV = 9ms/4ms/4mm slices/240×240mm) was obtained for verification of brain anatomical structures. An echo-planar-imaging sequence were used for the functional scans (TR/TE/slice/flip/FOV=2000ms/35ms/4mm slices/90°/220×220mm). fMRI data sets were analysed using SPM 8.0 involving preprocessing steps followed by t-contrast analysis for individuals and FFX analysis. In both with and without-loved-one conditions, neuronal responses were seen in the somatosensory gyrus, supramarginal gyrus, thalamus and insula regions, consistent with pain-related areas. FFX analysis showed that the presence of loved one produced more activation in the frontal and supramarginal gyrus during painful and non-painful stimulations compared to absence of a loved one. Brain response to pain is modulated by the presence of a loved one, causing more activation in the cognitive/emotional area i.e. 'love hurts'.

Effect of rhythmic photostimulation on monkeys with hyperkinesis of post-encephalitic genesis

NASA Technical Reports Server (NTRS)

Danilov, I. V.; Kudrayatseva, N. N.

1979-01-01

In hyperkinetic monkeys a response opposite to that of healthy monkeys was observed during rhythmic photostimulation (frequency 3, 9, 18, 20, and 25/sec), i.e., the hyperkinesis disappeared. The significance of rhythmic excitatory cycles for interconnections between different brain structures is discussed.

Principles of auditory processing differ between sensory and premotor structures of the songbird forebrain

PubMed Central

Vicario, David S.

2017-01-01

Sensory and motor brain structures work in collaboration during perception. To evaluate their respective contributions, the present study recorded neural responses to auditory stimulation at multiple sites simultaneously in both the higher-order auditory area NCM and the premotor area HVC of the songbird brain in awake zebra finches (Taeniopygia guttata). Bird’s own song (BOS) and various conspecific songs (CON) were presented in both blocked and shuffled sequences. Neural responses showed plasticity in the form of stimulus-specific adaptation, with markedly different dynamics between the two structures. In NCM, the response decrease with repetition of each stimulus was gradual and long-lasting and did not differ between the stimuli or the stimulus presentation sequences. In contrast, HVC responses to CON stimuli decreased much more rapidly in the blocked than in the shuffled sequence. Furthermore, this decrease was more transient in HVC than in NCM, as shown by differential dynamics in the shuffled sequence. Responses to BOS in HVC decreased more gradually than to CON stimuli. The quality of neural representations, computed as the mutual information between stimuli and neural activity, was higher in NCM than in HVC. Conversely, internal functional correlations, estimated as the coherence between recording sites, were greater in HVC than in NCM. The cross-coherence between the two structures was weak and limited to low frequencies. These findings suggest that auditory communication signals are processed according to very different but complementary principles in NCM and HVC, a contrast that may inform study of the auditory and motor pathways for human speech processing. NEW & NOTEWORTHY Neural responses to auditory stimulation in sensory area NCM and premotor area HVC of the songbird forebrain show plasticity in the form of stimulus-specific adaptation with markedly different dynamics. These two structures also differ in stimulus representations and internal functional correlations. Accordingly, NCM seems to process the individually specific complex vocalizations of others based on prior familiarity, while HVC responses appear to be modulated by transitions and/or timing in the ongoing sequence of sounds. PMID:28031398

Maternal Warm Responsiveness and Negativity Following Traumatic Brain Injury in Young Children

PubMed Central

Fairbanks, Joy M.; Brown, Tanya M.; Cassedy, Amy; Taylor, H. Gerry; Yeates, Keith O.; Wade, Shari L.

2014-01-01

Purpose/Objective To understand how traumatic brain injury (TBI) affects maternal warm responsiveness and negativity over the first 12 months following injury. Method/Design We used a concurrent cohort research design to examine dyadic interactions in young children with a TBI (n = 78) and a comparison group of young children with orthopedic injuries (OI; n = 112) and their families during the initial weeks following injury (i.e., baseline) and at two follow-up periods (approximately 6 and 12 months later). Trained raters coded videotaped interactions during a free play and structured teaching task for maternal warm responsiveness and negativity. Results Mothers in the complicated mild/moderate TBI group, but not those in the severe TBI group, exhibited significantly lower levels of maternal warm responsiveness than mothers in the OI group. However, these differences were observed only at baseline during free play and only at baseline and 6 months postinjury during the structured teaching task, suggesting diminishing adverse effects of complicated mild/moderate TBI on parenting over time postinjury. Analysis failed to reveal group differences in maternal negativity at any of the assessments. Across groups, lower socioeconomic status (SES) was associated with lower levels of warm responsiveness and higher levels of negativity. Conclusions/Implications These findings, though preliminary, indicate possible alterations in mother–child interactions in the months following a TBI. PMID:23978080

Model of brain activation predicts the neural collective influence map of the brain

PubMed Central

Morone, Flaviano; Roth, Kevin; Min, Byungjoon; Makse, Hernán A.

2017-01-01

Efficient complex systems have a modular structure, but modularity does not guarantee robustness, because efficiency also requires an ingenious interplay of the interacting modular components. The human brain is the elemental paradigm of an efficient robust modular system interconnected as a network of networks (NoN). Understanding the emergence of robustness in such modular architectures from the interconnections of its parts is a longstanding challenge that has concerned many scientists. Current models of dependencies in NoN inspired by the power grid express interactions among modules with fragile couplings that amplify even small shocks, thus preventing functionality. Therefore, we introduce a model of NoN to shape the pattern of brain activations to form a modular environment that is robust. The model predicts the map of neural collective influencers (NCIs) in the brain, through the optimization of the influence of the minimal set of essential nodes responsible for broadcasting information to the whole-brain NoN. Our results suggest intervention protocols to control brain activity by targeting influential neural nodes predicted by network theory. PMID:28351973

Recruiting specialized macrophages across the borders to restore brain functions.

PubMed

Corraliza, Inés

2014-01-01

Although is well accepted that the central nervous system has an immune privilege protected by the blood-brain barrier (BBB) and maintained by the glia, it is also known that in homeostatic conditions, peripheral immune cells are able to penetrate to the deepest regions of brain without altering the structural integrity of the BBB. Nearly all neurological diseases, including degenerative, autoimmune or infectious ones, compromising brain functions, develop with a common pattern of inflammation in which macrophages and microglia activation have been regarded often as the "bad guys." However, recognizing the huge heterogeneity of macrophage populations and also the different expression properties of microglia, there is increasing evidence of alternative conditions in which these cells, if primed and addressed in the correct direction, could be essential for reparative and regenerative functions. The main proposal of this review is to integrate studies about macrophage's biology at the brain borders where the ultimate challenge is to penetrate through the BBB and contribute to change or even stop the course of disease. Thanks to the efforts made in the last century, this special wall is currently recognized as a highly regulated cooperative structure, in which their components form neurovascular units. This new scenario prompted us to review the precise cross-talk between the mind and body modes of immune response.

Decision-making in the adolescent brain.

PubMed

Blakemore, Sarah-Jayne; Robbins, Trevor W

2012-09-01

Adolescence is characterized by making risky decisions. Early lesion and neuroimaging studies in adults pointed to the ventromedial prefrontal cortex and related structures as having a key role in decision-making. More recent studies have fractionated decision-making processes into its various components, including the representation of value, response selection (including inter-temporal choice and cognitive control), associative learning, and affective and social aspects. These different aspects of decision-making have been the focus of investigation in recent studies of the adolescent brain. Evidence points to a dissociation between the relatively slow, linear development of impulse control and response inhibition during adolescence versus the nonlinear development of the reward system, which is often hyper-responsive to rewards in adolescence. This suggests that decision-making in adolescence may be particularly modulated by emotion and social factors, for example, when adolescents are with peers or in other affective ('hot') contexts.

Time is of the Essence: A Review of Electroencephalography (EEG) and Event-Related Brain Potentials (ERPs) in Language Research.

PubMed

Beres, Anna M

2017-12-01

The discovery of electroencephalography (EEG) over a century ago has changed the way we understand brain structure and function, in terms of both clinical and research applications. This paper starts with a short description of EEG and then focuses on the event-related brain potentials (ERPs), and their use in experimental settings. It describes the typical set-up of an ERP experiment. A description of a number of ERP components typically involved in language research is presented. Finally, the advantages and disadvantages of using ERPs in language research are discussed. EEG has an extensive use in today's world, including medical, psychology, or linguistic research. The excellent temporal resolution of EEG information allows one to track a brain response in milliseconds and therefore makes it uniquely suited to research concerning language processing.

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

Roles of heat shock factor 1 in neuronal response to fetal environmental risks and its relevance to brain disorders.

PubMed

Hashimoto-Torii, Kazue; Torii, Masaaki; Fujimoto, Mitsuaki; Nakai, Akira; El Fatimy, Rachid; Mezger, Valerie; Ju, Min J; Ishii, Seiji; Chao, Shih-Hui; Brennand, Kristen J; Gage, Fred H; Rakic, Pasko

2014-05-07

Prenatal exposure of the developing brain to various environmental challenges increases susceptibility to late onset of neuropsychiatric dysfunction; still, the underlying mechanisms remain obscure. Here we show that exposure of embryos to a variety of environmental factors such as alcohol, methylmercury, and maternal seizure activates HSF1 in cerebral cortical cells. Furthermore, Hsf1 deficiency in the mouse cortex exposed in utero to subthreshold levels of these challenges causes structural abnormalities and increases seizure susceptibility after birth. In addition, we found that human neural progenitor cells differentiated from induced pluripotent stem cells derived from schizophrenia patients show higher variability in the levels of HSF1 activation induced by environmental challenges compared to controls. We propose that HSF1 plays a crucial role in the response of brain cells to prenatal environmental insults and may be a key component in the pathogenesis of late-onset neuropsychiatric disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Seeing left- or right-asymmetric tail wagging produces different emotional responses in dogs.

PubMed

Siniscalchi, Marcello; Lusito, Rita; Vallortigara, Giorgio; Quaranta, Angelo

2013-11-18

Left-right asymmetries in behavior associated with asymmetries in the brain are widespread in the animal kingdom, and the hypothesis has been put forward that they may be linked to animals' social behavior. Dogs show asymmetric tail-wagging responses to different emotive stimuli-the outcome of different activation of left and right brain structures controlling tail movements to the right and left side of the body. A crucial question, however, is whether or not dogs detect this asymmetry. Here we report that dogs looking at moving video images of conspecifics exhibiting prevalent left- or right-asymmetric tail wagging showed higher cardiac activity and higher scores of anxious behavior when observing left- rather than right-biased tail wagging. The finding that dogs are sensitive to the asymmetric tail expressions of other dogs supports the hypothesis of a link between brain asymmetry and social behavior and may prove useful to canine animal welfare theory and practice. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mechanisms of Endogenous Neuroprotective Effects of Astrocytes in Brain Injury

PubMed Central

2018-01-01

Astrocytes, once believed to serve only as “glue” for the structural support of neurons, have been demonstrated to serve critical functions for the maintenance and protection of neurons, especially under conditions of acute or chronic injury. There are at least seven distinct mechanisms by which astrocytes protect neurons from damage; these are (1) protection against glutamate toxicity, (2) protection against redox stress, (3) mediation of mitochondrial repair mechanisms, (4) protection against glucose-induced metabolic stress, (5) protection against iron toxicity, (6) modulation of the immune response in the brain, and (7) maintenance of tissue homeostasis in the presence of DNA damage. Astrocytes support these critical functions through specialized responses to stress or toxic conditions. The detoxifying activities of astrocytes are essential for maintenance of the microenvironment surrounding neurons and in whole tissue homeostasis. Improved understanding of the mechanisms by which astrocytes protect the brain could lead to the development of novel targets for the development of neuroprotective strategies.

A pediatric brain structure atlas from T1-weighted MR images

NASA Astrophysics Data System (ADS)

Shan, Zuyao Y.; Parra, Carlos; Ji, Qing; Ogg, Robert J.; Zhang, Yong; Laningham, Fred H.; Reddick, Wilburn E.

2006-03-01

In this paper, we have developed a digital atlas of the pediatric human brain. Human brain atlases, used to visualize spatially complex structures of the brain, are indispensable tools in model-based segmentation and quantitative analysis of brain structures. However, adult brain atlases do not adequately represent the normal maturational patterns of the pediatric brain, and the use of an adult model in pediatric studies may introduce substantial bias. Therefore, we proposed to develop a digital atlas of the pediatric human brain in this study. The atlas was constructed from T1 weighted MR data set of a 9 year old, right-handed girl. Furthermore, we extracted and simplified boundary surfaces of 25 manually defined brain structures (cortical and subcortical) based on surface curvature. Higher curvature surfaces were simplified with more reference points; lower curvature surfaces, with fewer. We constructed a 3D triangular mesh model for each structure by triangulation of the structure's reference points. Kappa statistics (cortical, 0.97; subcortical, 0.91) indicated substantial similarities between the mesh-defined and the original volumes. Our brain atlas and structural mesh models (www.stjude.org/BrainAtlas) can be used to plan treatment, to conduct knowledge and modeldriven segmentation, and to analyze the shapes of brain structures in pediatric patients.

Non-verbal emotion communication training induces specific changes in brain function and structure

PubMed Central

Kreifelts, Benjamin; Jacob, Heike; Brück, Carolin; Erb, Michael; Ethofer, Thomas; Wildgruber, Dirk

2013-01-01

The perception of emotional cues from voice and face is essential for social interaction. However, this process is altered in various psychiatric conditions along with impaired social functioning. Emotion communication trainings have been demonstrated to improve social interaction in healthy individuals and to reduce emotional communication deficits in psychiatric patients. Here, we investigated the impact of a non-verbal emotion communication training (NECT) on cerebral activation and brain structure in a controlled and combined functional magnetic resonance imaging (fMRI) and voxel-based morphometry study. NECT-specific reductions in brain activity occurred in a distributed set of brain regions including face and voice processing regions as well as emotion processing- and motor-related regions presumably reflecting training-induced familiarization with the evaluation of face/voice stimuli. Training-induced changes in non-verbal emotion sensitivity at the behavioral level and the respective cerebral activation patterns were correlated in the face-selective cortical areas in the posterior superior temporal sulcus and fusiform gyrus for valence ratings and in the temporal pole, lateral prefrontal cortex and midbrain/thalamus for the response times. A NECT-induced increase in gray matter (GM) volume was observed in the fusiform face area. Thus, NECT induces both functional and structural plasticity in the face processing system as well as functional plasticity in the emotion perception and evaluation system. We propose that functional alterations are presumably related to changes in sensory tuning in the decoding of emotional expressions. Taken together, these findings highlight that the present experimental design may serve as a valuable tool to investigate the altered behavioral and neuronal processing of emotional cues in psychiatric disorders as well as the impact of therapeutic interventions on brain function and structure. PMID:24146641

Non-verbal emotion communication training induces specific changes in brain function and structure.

PubMed

Kreifelts, Benjamin; Jacob, Heike; Brück, Carolin; Erb, Michael; Ethofer, Thomas; Wildgruber, Dirk

2013-01-01

The perception of emotional cues from voice and face is essential for social interaction. However, this process is altered in various psychiatric conditions along with impaired social functioning. Emotion communication trainings have been demonstrated to improve social interaction in healthy individuals and to reduce emotional communication deficits in psychiatric patients. Here, we investigated the impact of a non-verbal emotion communication training (NECT) on cerebral activation and brain structure in a controlled and combined functional magnetic resonance imaging (fMRI) and voxel-based morphometry study. NECT-specific reductions in brain activity occurred in a distributed set of brain regions including face and voice processing regions as well as emotion processing- and motor-related regions presumably reflecting training-induced familiarization with the evaluation of face/voice stimuli. Training-induced changes in non-verbal emotion sensitivity at the behavioral level and the respective cerebral activation patterns were correlated in the face-selective cortical areas in the posterior superior temporal sulcus and fusiform gyrus for valence ratings and in the temporal pole, lateral prefrontal cortex and midbrain/thalamus for the response times. A NECT-induced increase in gray matter (GM) volume was observed in the fusiform face area. Thus, NECT induces both functional and structural plasticity in the face processing system as well as functional plasticity in the emotion perception and evaluation system. We propose that functional alterations are presumably related to changes in sensory tuning in the decoding of emotional expressions. Taken together, these findings highlight that the present experimental design may serve as a valuable tool to investigate the altered behavioral and neuronal processing of emotional cues in psychiatric disorders as well as the impact of therapeutic interventions on brain function and structure.

Sensory Arsenal on the Stinger of the Parasitoid Jewel Wasp and Its Possible Role in Identifying Cockroach Brains

PubMed Central

Gal, Ram; Kaiser, Maayan; Haspel, Gal; Libersat, Frederic

2014-01-01

The parasitoid jewel wasp uses cockroaches as live food supply for its developing larva. To this end, the adult wasp stings a cockroach and injects venom directly inside its brain, turning the prey into a submissive ‘zombie’. Here, we characterize the sensory arsenal on the wasp’s stinger that enables the wasp to identify the brain target inside the cockroach’s head. An electron microscopy study of the stinger reveals (a) cuticular depressions innervated by a single mechanosensory neuron, which are presumably campaniform sensilla; and (b) dome-shaped structures innervated by a single mechanosensory neuron and 4–5 chemosensory neurons, which are presumably contact-chemoreceptive sensilla. Extracellular electrophysiological recordings from stinger afferents show increased firing rate in response to mechanical stimulation with agarose. This response is direction-selective and depends upon the concentration (density) of the agarose, such that the most robust response is evoked when the stinger is stimulated in the distal-to-proximal direction (concomitant with the penetration during the natural stinging behavior) and penetrating into relatively hard (0.75%–2.5%) agarose pellets. Accordingly, wasps demonstrate a normal stinging behavior when presented with cockroaches in which the brain was replaced with a hard (2.5%) agarose pellet. Conversely, wasps demonstrate a prolonged stinging behavior when the cockroach brain was either removed or replaced by a soft (0.5%) agarose pellet, or when stinger sensory organs were ablated prior to stinging. We conclude that the parasitoid jewel wasp uses at least mechanosensory inputs from its stinger to identify the brain within the head capsule of the cockroach prey. PMID:24586962

Effects of Insulin Detemir and NPH Insulin on Body Weight and Appetite-Regulating Brain Regions in Human Type 1 Diabetes: A Randomized Controlled Trial

PubMed Central

van Golen, Larissa W.; Veltman, Dick J.; IJzerman, Richard G.; Deijen, Jan Berend; Heijboer, Annemieke C.; Barkhof, Frederik; Drent, Madeleine L.; Diamant, Michaela

2014-01-01

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. Trial Registration ClinicalTrials.gov NCT00626080. PMID:24739875

Effects of insulin detemir and NPH insulin on body weight and appetite-regulating brain regions in human type 1 diabetes: a randomized controlled trial.

PubMed

van Golen, Larissa W; Veltman, Dick J; IJzerman, Richard G; Deijen, Jan Berend; Heijboer, Annemieke C; Barkhof, Frederik; Drent, Madeleine L; Diamant, Michaela

2014-01-01

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. ClinicalTrials.gov NCT00626080.

Visual and auditory steady-state responses in attention-deficit/hyperactivity disorder.

PubMed

Khaleghi, Ali; Zarafshan, Hadi; Mohammadi, Mohammad Reza

2018-05-22

We designed a study to investigate the patterns of the steady-state visual evoked potential (SSVEP) and auditory steady-state response (ASSR) in adolescents with attention-deficit/hyperactivity disorder (ADHD) when performing a motor response inhibition task. Thirty 12- to 18-year-old adolescents with ADHD and 30 healthy control adolescents underwent an electroencephalogram (EEG) examination during steady-state stimuli when performing a stop-signal task. Then, we calculated the amplitude and phase of the steady-state responses in both visual and auditory modalities. Results showed that adolescents with ADHD had a significantly poorer performance in the stop-signal task during both visual and auditory stimuli. The SSVEP amplitude of the ADHD group was larger than that of the healthy control group in most regions of the brain, whereas the ASSR amplitude of the ADHD group was smaller than that of the healthy control group in some brain regions (e.g., right hemisphere). In conclusion, poorer task performance (especially inattention) and neurophysiological results in ADHD demonstrate a possible impairment in the interconnection of the association cortices in the parietal and temporal lobes and the prefrontal cortex. Also, the motor control problems in ADHD may arise from neural deficits in the frontoparietal and occipitoparietal systems and other brain structures such as cerebellum.

Social re-orientation and brain development: An expanded and updated view.

PubMed

Nelson, Eric E; Jarcho, Johanna M; Guyer, Amanda E

2016-02-01

Social development has been the focus of a great deal of neuroscience based research over the past decade. In this review, we focus on providing a framework for understanding how changes in facets of social development may correspond with changes in brain function. We argue that (1) distinct phases of social behavior emerge based on whether the organizing social force is the mother, peer play, peer integration, or romantic intimacy; (2) each phase is marked by a high degree of affect-driven motivation that elicits a distinct response in subcortical structures; (3) activity generated by these structures interacts with circuits in prefrontal cortex that guide executive functions, and occipital and temporal lobe circuits, which generate specific sensory and perceptual social representations. We propose that the direction, magnitude and duration of interaction among these affective, executive, and perceptual systems may relate to distinct sensitive periods across development that contribute to establishing long-term patterns of brain function and behavior. Published by Elsevier Ltd.

The Role of Medical Imaging in the Recharacterization of Mild Traumatic Brain Injury Using Youth Sports as a Laboratory.

PubMed

Talavage, Thomas M; Nauman, Eric A; Leverenz, Larry J

2015-01-01

The short- and long-term impact of mild traumatic brain injury (TBI) is an increasingly vital concern for both military and civilian personnel. Such injuries produce significant social and financial burdens and necessitate improved diagnostic and treatment methods. Recent integration of neuroimaging and biomechanical studies in youth collision-sport athletes has revealed that significant alterations in brain structure and function occur even in the absence of traditional clinical markers of "concussion." While task performance is maintained, athletes exposed to repetitive head accelerations exhibit structural changes to the underlying white matter, altered glial cell metabolism, aberrant vascular response, and marked changes in functional network behavior. Moreover, these changes accumulate with accrued years of exposure, suggesting a cumulative trauma mechanism that may culminate in categorization as "concussion" and long-term neurological deficits. The goal of this review is to elucidate the role of medical imaging in recharacterizing TBI, as a whole, to better identify at-risk individuals and improve the development of preventative and interventional approaches.

Deep Brain Stimulation of the Memory Circuit: Improving Cognition in Alzheimer's Disease.

PubMed

Posporelis, Sotirios; David, Anthony S; Ashkan, Keyoumars; Shotbolt, Paul

2018-05-26

Deep brain stimulation (DBS) is an effective invasive treatment for a wide range of neurological and psychiatric disorders. Neurosurgically implanted electrodes deliver stimulation of pre-programmed amplitude, frequency, and pulse width within deep brain structures; those settings can be adjusted at a later stage according to individual needs for optimal response. This results in variable effects dependent on the targeted region. An established treatment for movement disorders, the effectiveness of DBS in dementia remains under investigation. Translational studies have uncovered a pro-cognitive effect mediated by changes on cellular as well as network level. Several groups have attempted to examine the benefits of DBS in Alzheimer's disease; differences in inclusion criteria and methodology make generalization of results difficult. This review aims to summarize all completed and ongoing human studies of DBS in Alzheimer's disease. The results are classified by targeted anatomical structure. Future directions, as well as economical and ethical arguments, are explored in the final section.

A thesaurus for a neural population code

PubMed Central

Ganmor, Elad; Segev, Ronen; Schneidman, Elad

2015-01-01

Information is carried in the brain by the joint spiking patterns of large groups of noisy, unreliable neurons. This noise limits the capacity of the neural code and determines how information can be transmitted and read-out. To accurately decode, the brain must overcome this noise and identify which patterns are semantically similar. We use models of network encoding noise to learn a thesaurus for populations of neurons in the vertebrate retina responding to artificial and natural videos, measuring the similarity between population responses to visual stimuli based on the information they carry. This thesaurus reveals that the code is organized in clusters of synonymous activity patterns that are similar in meaning but may differ considerably in their structure. This organization is highly reminiscent of the design of engineered codes. We suggest that the brain may use this structure and show how it allows accurate decoding of novel stimuli from novel spiking patterns. DOI: http://dx.doi.org/10.7554/eLife.06134.001 PMID:26347983

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

PubMed

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

2008-01-01

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

Brain Responses to Filled Gaps

ERIC Educational Resources Information Center

Hestvik, Arild; Maxfield, Nathan; Schwartz, Richard G.; Shafer, Valerie

2007-01-01

An unresolved issue in the study of sentence comprehension is whether the process of gap-filling is mediated by the construction of empty categories (traces), or whether the parser relates fillers directly to the associated verb's argument structure. We conducted an event-related potentials (ERP) study that used the violation paradigm to examine…

Audio-tactile integration and the influence of musical training.

PubMed

Kuchenbuch, Anja; Paraskevopoulos, Evangelos; Herholz, Sibylle C; Pantev, Christo

2014-01-01

Perception of our environment is a multisensory experience; information from different sensory systems like the auditory, visual and tactile is constantly integrated. Complex tasks that require high temporal and spatial precision of multisensory integration put strong demands on the underlying networks but it is largely unknown how task experience shapes multisensory processing. Long-term musical training is an excellent model for brain plasticity because it shapes the human brain at functional and structural levels, affecting a network of brain areas. In the present study we used magnetoencephalography (MEG) to investigate how audio-tactile perception is integrated in the human brain and if musicians show enhancement of the corresponding activation compared to non-musicians. Using a paradigm that allowed the investigation of combined and separate auditory and tactile processing, we found a multisensory incongruency response, generated in frontal, cingulate and cerebellar regions, an auditory mismatch response generated mainly in the auditory cortex and a tactile mismatch response generated in frontal and cerebellar regions. The influence of musical training was seen in the audio-tactile as well as in the auditory condition, indicating enhanced higher-order processing in musicians, while the sources of the tactile MMN were not influenced by long-term musical training. Consistent with the predictive coding model, more basic, bottom-up sensory processing was relatively stable and less affected by expertise, whereas areas for top-down models of multisensory expectancies were modulated by training.

Preterm EEG: a multimodal neurophysiological protocol.

PubMed

Stjerna, Susanna; Voipio, Juha; Metsäranta, Marjo; Kaila, Kai; Vanhatalo, Sampsa

2012-02-18

Since its introduction in early 1950s, electroencephalography (EEG) has been widely used in the neonatal intensive care units (NICU) for assessment and monitoring of brain function in preterm and term babies. Most common indications are the diagnosis of epileptic seizures, assessment of brain maturity, and recovery from hypoxic-ischemic events. EEG recording techniques and the understanding of neonatal EEG signals have dramatically improved, but these advances have been slow to penetrate through the clinical traditions. The aim of this presentation is to bring theory and practice of advanced EEG recording available for neonatal units. In the theoretical part, we will present animations to illustrate how a preterm brain gives rise to spontaneous and evoked EEG activities, both of which are unique to this developmental phase, as well as crucial for a proper brain maturation. Recent animal work has shown that the structural brain development is clearly reflected in early EEG activity. Most important structures in this regard are the growing long range connections and the transient cortical structure, subplate. Sensory stimuli in a preterm baby will generate responses that are seen at a single trial level, and they have underpinnings in the subplate-cortex interaction. This brings neonatal EEG readily into a multimodal study, where EEG is not only recording cortical function, but it also tests subplate function via different sensory modalities. Finally, introduction of clinically suitable dense array EEG caps, as well as amplifiers capable of recording low frequencies, have disclosed multitude of brain activities that have as yet been overlooked. In the practical part of this video, we show how a multimodal, dense array EEG study is performed in neonatal intensive care unit from a preterm baby in the incubator. The video demonstrates preparation of the baby and incubator, application of the EEG cap, and performance of the sensory stimulations.

Can brain scans prove criminals unaccountable?

PubMed Central

Roache, Rebecca

2014-01-01

Leonard Berlin reports that neuroscientific data play an increasing role in court. They have been used to argue that criminals are not morally responsible for their behaviour because their brains are ‘faulty’, and there is evidence that such data lead judges to pass more lenient sentences. I raise two concerns about the view that neuroscience can show criminals not to be morally responsible: That the brains of (say) violent criminals differ from most people’s brains does not straightforwardly show that violent criminals are less morally responsible. Behavioral states arise inter alia from brain states, and since violent criminals’ behavioral states differ from those of most people, it is unsurprising that violent criminals’ brains should differ from most people’s brains. This no more shows violent criminals to have diminished moral responsibility than differences between the brains of cheerful and uncheerful people show either group to have diminished moral responsibility.Those who view brain abnormalities as evidence of reduced moral responsibility rely on the assumptions that people with normal brains have free will and that we know what sorts of brain activity undermine free will. However, both of these assumptions are highly controversial. As a result, neuroscience is not a reliable source of information about moral responsibility. I conclude that, until we settle whether and under what circumstances brain activity is incompatible with free will, neuroscience cannot tell us anything useful about criminal accountability. PMID:25009758

A quantitative and qualitative review of the effects of testosterone on the function and structure of the human social-emotional brain.

PubMed

Heany, Sarah J; van Honk, Jack; Stein, Dan J; Brooks, Samantha J

2016-02-01

Social and affective research in humans is increasingly using functional and structural neuroimaging techniques to aid the understanding of how hormones, such as testosterone, modulate a wide range of psychological processes. We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies of testosterone administration, and of fMRI studies that measured endogenous levels of the hormone, in relation to social and affective stimuli. Furthermore, we conducted a review of structural MRI i.e. voxel based morphometry (VBM) studies which considered brain volume in relation to testosterone levels in adults and in children. In the included testosterone administration fMRI studies, which consisted of female samples only, bilateral amygdala/parahippocampal regions as well as the right caudate were significantly activated by social-affective stimuli in the testosterone condition. In the studies considering endogenous levels of testosterone, stimuli-invoked activations relating to testosterone levels were noted in the bilateral amygdala/parahippocampal regions and the brainstem. When the endogenous testosterone studies were split by sex, the significant activation of the brain stem was seen in the female samples only. Significant stimuli-invoked deactivations relating to endogenous testosterone levels were also seen in the right and left amygdala/parahippocampal regions studies. The findings of the VBM studies were less consistent. In adults larger volumes in the limbic and temporal regions were associated with higher endogenous testosterone. In children, boys showed a positive correlation between testosterone and brain volume in many regions, including the amygdala, as well as global grey matter volume, while girls showed a neutral or negative association between testosterone levels and many brain volumes. In conclusion, amygdalar and parahippocampal regions appear to be key target regions for the acute actions of testosterone in response to social and affective stimuli, while neurodevelopmentally the volumes of a broader network of brain structures are associated with testosterone levels in a sexually dimorphic manner.

Born criminal? Differences in structural, functional and behavioural lateralization between criminals and noncriminals.

PubMed

Savopoulos, Priscilla; Lindell, Annukka K

2018-02-15

Over 100 years ago Lombroso [(1876/2006). Criminal man. Durham: Duke University Press] proposed a biological basis for criminality. Based on inspection of criminals' skulls he theorized that an imbalance of the cerebral hemispheres was amongst 18 distinguishing features of the criminal brain. Specifically, criminals were less lateralized than noncriminals. As the advent of neuroscientific techniques makes more fine-grained inspection of differences in brain structure and function possible, we review criminals' and noncriminals' structural, functional, and behavioural lateralization to evaluate the merits of Lombroso's thesis and investigate the evidence for the biological underpinning of criminal behaviour. Although the body of research is presently small, it appears consistent with Lombroso's proposal: criminal psychopaths' brains show atypical structural asymmetries, with reduced right hemisphere grey and white matter volumes, and abnormal interhemispheric connectivity. Functional asymmetries are also atypical, with criminal psychopaths showing a less lateralized cortical response than noncriminals across verbal, visuo-spatial, and emotional tasks. Finally, the incidence of non-right-handedness is higher in criminal than non-criminal populations, consistent with reduced cortical lateralization. Thus despite Lombroso's comparatively primitive and inferential research methods, his conclusion that criminals' lateralization differs from that of noncriminals is borne out by the neuroscientific research. How atypical cortical asymmetries predispose criminal behaviour remains to be determined.

A novel fibrous duct structure discovered in the brain meninges by using polarized light microscopy

NASA Astrophysics Data System (ADS)

Nam, Min-Ho; Jung, Sharon Jiyoon; Soh, Kwang-Sup; Lim, Jaekwan; Seo, Eunseok; Lim, Jun; Baek, Miok; Lee, Sang Joon

2016-05-01

We have previously reported the discovery of a novel fibrous structure (NFS) consisting of unidirectionally arranged collagen fibers in the spinal pia mater. Due to its unique structure, it was easily detected using polarized light microscopy. In the current study, we describe the discovery of a similar NFS in the brain meninges of rats by using polarized light microscopy. This NFS is located beneath the superior sagittal sinus. Initially, we systemically analyzed the polarization properties of the NFS. The change in the light intensity of the NFS, with respect to the polarization angle, was eight times greater than that of blood vessels, showing that the collagen fibers are oriented in a particular direction with almost perfect parallelism (0.99). The orientation angle of the polarization ellipse confirmed the orientation of the collagen fibers in the NFS. Histological studies further confirmed that the unidirectionally arranged collagen fibers were responsible for this distinct polarization property. Surprisingly, X-ray microtomography and 3D confocal imaging revealed that the NFS contains within it a duct structure, a putative primo vessel. In conclusion, we report a NFS in the brain meninges, detected by using polarized light microscopy, that provides space for a putative primo vessel, not a blood vessel.

The crystal structure of human GlnRS provides basis for the development of neurological disorders

DOE PAGES

Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen; ...

2016-02-10

Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggestmore » that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords« less

Sparsity enables estimation of both subcortical and cortical activity from MEG and EEG

PubMed Central

Krishnaswamy, Pavitra; Obregon-Henao, Gabriel; Ahveninen, Jyrki; Khan, Sheraz; Iglesias, Juan Eugenio; Hämäläinen, Matti S.; Purdon, Patrick L.

2017-01-01

Subcortical structures play a critical role in brain function. However, options for assessing electrophysiological activity in these structures are limited. Electromagnetic fields generated by neuronal activity in subcortical structures can be recorded noninvasively, using magnetoencephalography (MEG) and electroencephalography (EEG). However, these subcortical signals are much weaker than those generated by cortical activity. In addition, we show here that it is difficult to resolve subcortical sources because distributed cortical activity can explain the MEG and EEG patterns generated by deep sources. We then demonstrate that if the cortical activity is spatially sparse, both cortical and subcortical sources can be resolved with M/EEG. Building on this insight, we develop a hierarchical sparse inverse solution for M/EEG. We assess the performance of this algorithm on realistic simulations and auditory evoked response data, and show that thalamic and brainstem sources can be correctly estimated in the presence of cortical activity. Our work provides alternative perspectives and tools for characterizing electrophysiological activity in subcortical structures in the human brain. PMID:29138310

The crystal structure of human GlnRS provides basis for the development of neurological disorders

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

Ognjenovic, Jana; Wu, Jiang; Matthies, Doreen

Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translation of glutamine codons. Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understood mechanism. Herein, we present crystal structures of the wild type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain organization of the intact enzyme and the structure of the functionally important N-terminal domain (NTD). Pathological mutations mapping in the NTD alter the domain structure, and decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domain induce misfolding of the enzyme. Our results suggestmore » that the reduced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development. As a result, this report broadens the spectrum of brain pathologies elicited by protein misfolding and provides a paradigm for understanding the role of mutations in aminoacyl-tRNA synthetases in neurological diseases. Keywords« less

Gut-Brain Axis and Behavior.

PubMed

Martin, Clair R; Mayer, Emeran A

2017-01-01

In the last 5 years, interest in the interactions among the gut microbiome, brain, and behavior has exploded. Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food intake. Limited, but growing, clinical evidence comes primarily from associations of gut microbial composition and function to behavioral and clinical features and brain structure and function. Converging evidence suggests that the brain and the gut microbiota are in bidirectional communication. Observed dysbiotic states in depression, chronic stress, and autism may reflect altered brain signaling to the gut, while altered gut microbial signaling to the brain may play a role in reinforcing brain alterations. On the other hand, primary dysbiotic states due to Western diets may signal to the brain, altering ingestive behavior. While studies performed in patients with depression and rodent models generated by fecal microbial transfer from such patients suggest causation, evidence for an influence of acute gut microbial alterations on human behavioral and clinical parameters is lacking. Only recently has an open-label microbial transfer therapy in children with autism tentatively validated the gut microbiota as a therapeutic target. The translational potential of preclinical findings remains unclear without further clinical investigation. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

Atomoxetine restores the response inhibition network in Parkinson's disease.

PubMed

Rae, Charlotte L; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E; Jones, P Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J; Barker, Roger A; Robbins, Trevor W; Rowe, James B

2016-08-01

Parkinson's disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson's disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson's disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson's disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson's disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced stop-signal reaction time) following atomoxetine correlated with structural connectivity as measured by the fractional anisotropy in the white matter underlying the inferior frontal gyrus. Using multiple regression models, we examined the factors that influenced the individual differences in the response to atomoxetine: the reduction in stop-signal reaction time correlated with structural connectivity and baseline performance, while disease severity and drug plasma level predicted the change in fronto-striatal effective connectivity following atomoxetine. These results suggest that (i) atomoxetine increases sensitivity of the inferior frontal gyrus to afferent inputs from the pre-supplementary motor cortex; (ii) atomoxetine can enhance downstream modulation of frontal-subcortical connections for response inhibition; and (iii) the behavioural consequences of treatment are dependent on fronto-striatal structural connections. The individual differences in behavioural responses to atomoxetine highlight the need for patient stratification in future clinical trials of noradrenergic therapies for Parkinson's disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Silicon chip with capacitors and transistors for interfacing organotypic brain slice of rat hippocampus.

PubMed

Hutzler, Michael; Fromherz, Peter

2004-04-01

Probing projections between brain areas and their modulation by synaptic potentiation requires dense arrays of contacts for noninvasive electrical stimulation and recording. Semiconductor technology is able to provide planar arrays with high spatial resolution to be used with planar neuronal structures such as organotypic brain slices. To address basic methodical issues we developed a silicon chip with simple arrays of insulated capacitors and field-effect transistors for stimulation of neuronal activity and recording of evoked field potentials. Brain slices from rat hippocampus were cultured on that substrate. We achieved local stimulation of the CA3 region by applying defined voltage pulses to the chip capacitors. Recording of resulting local field potentials in the CA1 region was accomplished with transistors. The relationship between stimulation and recording was rationalized by a sheet conductor model. By combining a row of capacitors with a row of transistors we determined a simple stimulus-response matrix from CA3 to CA1. Possible contributions of inhomogeneities of synaptic projection, of tissue structure and of neuroelectronic interfacing were considered. The study provides the basis for a development of semiconductor chips with high spatial resolution that are required for long-term studies of topographic mapping.

Psychophysiological correlates of aggression and violence: an integrative review.

PubMed

Patrick, Christopher J

2008-08-12

This paper reviews existing psychophysiological studies of aggression and violent behaviour including research employing autonomic, electrocortical and neuroimaging measures. Robust physiological correlates of persistent aggressive behaviour evident in this literature include low baseline heart rate, enhanced autonomic reactivity to stressful or aversive stimuli, enhanced EEG slow wave activity, reduced P300 brain potential response and indications from structural and functional neuroimaging studies of dysfunction in frontocortical and limbic brain regions that mediate emotional processing and regulation. The findings are interpreted within a conceptual framework that draws on two integrative models in the literature. The first is a recently developed hierarchical model of impulse control (externalizing) problems, in which various disinhibitory syndromes including aggressive and addictive behaviours of different kinds are seen as arising from common as well as distinctive aetiologic factors. This model represents an approach to organizing these various interrelated phenotypes and investigating their common and distinctive aetiologic substrates. The other is a neurobiological model that posits impairments in affective regulatory circuits in the brain as a key mechanism for impulsive aggressive behaviour. This model provides a perspective for integrating findings from studies employing different measures that have implicated varying brain structures and physiological systems in violent and aggressive behaviour.

Commentary: physical approaches for the treatment of epilepsy: electrical and magnetic stimulation and cooling.

PubMed

Löscher, Wolfgang; Cole, Andrew J; McLean, Michael J

2009-04-01

Physical approaches for the treatment of epilepsy currently under study or development include electrical or magnetic brain stimulators and cooling devices, each of which may be implanted or applied externally. Some devices may stimulate peripheral structures, whereas others may be implanted directly into the brain. Stimulation may be delivered chronically, intermittently, or in response to either manual activation or computer-based detection of events of interest. Physical approaches may therefore ultimately be appropriate for seizure prophylaxis by causing a modification of the underlying substrate, presumably with a reduction in the intrinsic excitability of cerebral structures, or for seizure termination, by interfering with the spontaneous discharge of pathological neuronal networks. Clinical trials of device-based therapies are difficult due to ethical issues surrounding device implantation, problems with blinding, potential carryover effects that may occur in crossover designs if substrate modification occurs, and subject heterogeneity. Unresolved issues in the development of physical treatments include optimization of stimulation parameters, identification of the optimal volume of brain to be stimulated, development of adequate power supplies to stimulate the necessary areas, and a determination that stimulation itself does not promote epileptogenesis or adverse long-term effects on normal brain function.

Brain Correlates of Self-Evaluation Deficits in Schizophrenia: A Combined Functional and Structural MRI Study

PubMed Central

Fan, Fengmei; Zou, Yizhuang; Jin, Zhen; Zen, Yawei; Zhu, Xiaolin; Yang, Fude; Tan, Yunlong; Zhou, Dongfeng

2015-01-01

Self-evaluation plays an important role in adaptive functioning and is a process that is typically impaired in patients with schizophrenia. Underlying neural mechanisms for this dysfunction may be associated with manifested psychosis. However, the brain substrates underlying this deficit are not well known. The present study used brain blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) and gray matter voxel-based morphometry to explore the functional and structural brain correlates of self-evaluation deficits in schizophrenia. Eighteen patients with schizophrenia and 17 healthy controls were recruited and asked to judge whether a set of personality-trait adjectives were appropriate for describing themselves, a familiar other, or whether the adjectives were of positive or negative valence. Patients had slower response times for negative trait attributions than controls did; responses to positive trait attributions were faster than those for negative traits among the patient group, while no differences were observed in the control group. Control subjects showed greater activation within the dorsal medial prefrontal cortex (dMPFC) and the anterior cingulate cortex (ACC) than the patient group during the self-evaluation > semantic positivity-evaluation contrast. Patients showed greater activation mainly within the posterior cingulate gyrus (PCC) as compared to controls for the other-evaluation > semantic positivity-evaluation contrast. Furthermore, gray matter volume was reduced in the MPFC, temporal lobe, cuneus, and the dorsal lateral prefrontal cortex (DLPFC) among the patient group when compared to controls. The present study adds to previous findings regarding self- and other-referential processing in schizophrenia, providing support for neurobiological models of self-reflection impairment. PMID:26406464

Functional localization of a "Time Keeper" function separate from attentional resources and task strategy.

PubMed

Tracy, J I; Faro, S H; Mohamed, F B; Pinsk, M; Pinus, A

2000-03-01

The functional neuroanatomy of time estimation has not been well-documented. This research investigated the fMRI measured brain response to an explicit, prospective time interval production (TIP) task. The study tested for the presence of brain activity reflecting a primary time keeper function, distinct from the brain systems involved either in conscious strategies to monitor time or attentional resource and other cognitive processes to accomplish the task. In the TIP task participants were given a time interval and asked to indicate when it elapsed. Two control tasks (counting forwards, backwards) were administered, in addition to a dual task format of the TIP task. Whole brain images were collected at 1.5 Tesla. Analyses (n = 6) yielded a statistical parametric map (SPM ¿z¿) reflecting time keeping and not strategy (counting, number manipulation) or attention resource utilization. Additional SPM ¿z¿s involving activation associated with the accuracy and magnitude the of time estimation response are presented. Results revealed lateral cerebellar and inferior temporal lobe activation were associated with primary time keeping. Behavioral data provided evidence that the procedures for the explicit time judgements did not occur automatically and utilized controlled processes. Activation sites associated with accuracy, magnitude, and the dual task provided indications of the other structures involved in time estimation that implemented task components related to controlled processing. The data are consistent with prior proposals that the cerebellum is a repository of codes for time processing, but also implicate temporal lobe structures for this type of time estimation task. Copyright 2000 Academic Press.

Excessive coupling of the salience network with intrinsic neurocognitive brain networks during rectal distension in adolescents with irritable bowel syndrome: a preliminary report

PubMed Central

Liu, Xiaolin; Silverman, Alan; Kern, Mark; Ward, B. Douglas; Li, Shi-Jiang; Shaker, Reza; Sood, Manu R.

2015-01-01

Background The neural network mechanisms underlying visceral hypersensitivity in irritable bowel syndrome (IBS) are incompletely understood. It has been proposed that an intrinsic salience network plays an important role in chronic pain and IBS symptoms. Using neuroimaging, we examined brain responses to rectal distension in adolescent IBS patients, focusing on determining the alteration of salience network integrity in IBS and its functional implications in current theoretical frameworks. We hypothesized that (1) brain responses to visceral stimulation in adolescents are similar to those in adults, and (2) IBS is associated with an altered salience network interaction with other neurocognitive networks, particularly the default mode network (DMN) and executive control network (ECN), as predicted by the theoretical models. Methods IBS patients and controls received subliminal and liminal rectal distension during imaging. Stimulus-induced brain activations were determined. Salience network integrity was evaluated by functional connectivity of its seed regions activated by rectal distension in the insular and cingulate cortices. Key Results Compared with controls, IBS patients demonstrated greater activation to rectal distension in neural structures of the homeostatic afferent and emotional arousal networks, especially the anterior cingulate and insular cortices. Greater brain responses to liminal vs. subliminal distension were observed in both groups. Particularly, IBS is uniquely associated with an excessive coupling of the salience network with the DMN and ECN in their key frontal and parietal node areas. Conclusions & Inferences Our study provided consistent evidence supporting the theoretical predictions of altered salience network functioning as a neuropathological mechanism of IBS symptoms. PMID:26467966

Brain functional BOLD perturbation modelling for forward fMRI and inverse mapping

PubMed Central

Robinson, Jennifer; Calhoun, Vince

2018-01-01

Purpose To computationally separate dynamic brain functional BOLD responses from static background in a brain functional activity for forward fMRI signal analysis and inverse mapping. Methods A brain functional activity is represented in terms of magnetic source by a perturbation model: χ = χ0 +δχ, with δχ for BOLD magnetic perturbations and χ0 for background. A brain fMRI experiment produces a timeseries of complex-valued images (T2* images), whereby we extract the BOLD phase signals (denoted by δP) by a complex division. By solving an inverse problem, we reconstruct the BOLD δχ dataset from the δP dataset, and the brain χ distribution from a (unwrapped) T2* phase image. Given a 4D dataset of task BOLD fMRI, we implement brain functional mapping by temporal correlation analysis. Results Through a high-field (7T) and high-resolution (0.5mm in plane) task fMRI experiment, we demonstrated in detail the BOLD perturbation model for fMRI phase signal separation (P + δP) and reconstructing intrinsic brain magnetic source (χ and δχ). We also provided to a low-field (3T) and low-resolution (2mm) task fMRI experiment in support of single-subject fMRI study. Our experiments show that the δχ-depicted functional map reveals bidirectional BOLD χ perturbations during the task performance. Conclusions The BOLD perturbation model allows us to separate fMRI phase signal (by complex division) and to perform inverse mapping for pure BOLD δχ reconstruction for intrinsic functional χ mapping. The full brain χ reconstruction (from unwrapped fMRI phase) provides a new brain tissue image that allows to scrutinize the brain tissue idiosyncrasy for the pure BOLD δχ response through an automatic function/structure co-localization. PMID:29351339

Interactions Between Stress and Sex in Microbial Responses Within the Microbiota-Gut-Brain Axis in a Mouse Model.

PubMed

Tsilimigras, Matthew C B; Gharaibeh, Raad Z; Sioda, Michael; Gray, Laura; Fodor, Anthony A; Lyte, Mark

2018-05-01

Animal models are frequently used to examine stress response, but experiments seldom include females. The connection between the microbiota-gut-brain axis and behavioral stress response is investigated here using a mixed-sex mouse cohort. CF-1 mice underwent alternating days of restraint and forced swim for 19 days (male n = 8, female n = 8) with matching numbers of control animals at which point the 16S rRNA genes of gut microbiota were sequenced. Mixed linear models accounting for stress status and sex with individuals nested in cage to control for cage effects evaluated these data. Murine behaviors in elevated plus-maze, open-field, and light/dark box were investigated. Community-level associations with sex, stress, and their interaction were significant. Males had higher microbial diversity than females (p = .025). Of the 638 operational taxonomic units detected in at least 25% of samples, 94 operational taxonomic units were significant: 31 (stress), 61 (sex), and 34 (sex-stress interaction). Twenty of the 39 behavioral measures were significant for stress, 3 for sex, and 6 for sex-stress. However, no significant associations between behavioral measures and specific microbes were detected. These data suggest sex influences stress response and the microbiota-gut-brain axis and that studies of behavior and the microbiome therefore benefit from consideration of how sex differences drive behavior and microbial community structure. Host stress resilience and absence of associations between stress-induced behaviors with specific microbes suggests that hypothalamic-pituitary-adrenal axis activation represents a threshold for microbial influence on host behavior. Future studies are needed in examining the intersection of sex, stress response, and the microbiota-gut-brain axis.

The medial frontal cortex contributes to but does not organize rat exploratory behavior.

PubMed

Blankenship, Philip A; Stuebing, Sarah L; Winter, Shawn S; Cheatwood, Joseph L; Benson, James D; Whishaw, Ian Q; Wallace, Douglas G

2016-11-12

Animals use multiple strategies to maintain spatial orientation. Dead reckoning is a form of spatial navigation that depends on self-movement cue processing. During dead reckoning, the generation of self-movement cues from a starting position to an animal's current position allow for the estimation of direction and distance to the position movement originated. A network of brain structures has been implicated in dead reckoning. Recent work has provided evidence that the medial frontal cortex may contribute to dead reckoning in this network of brain structures. The current study investigated the organization of rat exploratory behavior subsequent to medial frontal cortex aspiration lesions under light and dark conditions. Disruptions in exploratory behavior associated with medial frontal lesions were consistent with impaired motor coordination, response inhibition, or egocentric reference frame. These processes are necessary for spatial orientation; however, they are not sufficient for self-movement cue processing. Therefore it is possible that the medial frontal cortex provides processing resources that support dead reckoning in other brain structures but does not of itself compute the kinematic details of dead reckoning. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Manipulating neural activity in physiologically classified neurons: triumphs and challenges

PubMed Central

Gore, Felicity; Schwartz, Edmund C.; Salzman, C. Daniel

2015-01-01

Understanding brain function requires knowing both how neural activity encodes information and how this activity generates appropriate responses. Electrophysiological, imaging and immediate early gene immunostaining studies have been instrumental in identifying and characterizing neurons that respond to different sensory stimuli, events and motor actions. Here we highlight approaches that have manipulated the activity of physiologically classified neurons to determine their role in the generation of behavioural responses. Previous experiments have often exploited the functional architecture observed in many cortical areas, where clusters of neurons share response properties. However, many brain structures do not exhibit such functional architecture. Instead, neurons with different response properties are anatomically intermingled. Emerging genetic approaches have enabled the identification and manipulation of neurons that respond to specific stimuli despite the lack of discernable anatomical organization. These approaches have advanced understanding of the circuits mediating sensory perception, learning and memory, and the generation of behavioural responses by providing causal evidence linking neural response properties to appropriate behavioural output. However, significant challenges remain for understanding cognitive processes that are probably mediated by neurons with more complex physiological response properties. Currently available strategies may prove inadequate for determining how activity in these neurons is causally related to cognitive behaviour. PMID:26240431

[See the thinking brain: a story about water].

PubMed

Le Bihan, D

2008-01-01

Among the astonishing Einstein's papers from 1905, there is one which unexpectedly gave birth to a powerful method to explore the brain. Molecular diffusion was explained by Einstein on the basis of the random translational motion of molecules which results from their thermal energy. In the mid 1980s it was shown that water diffusion in the brain could be imaged using MRI. During their random displacements water molecules probe tissue structure at a microscopic scale, interacting with cell membranes and, thus, providing unique information on the functional architecture of tissues. A dramatic application of diffusion MRI has been brain ischemia, following the discovery that water diffusion drops immediately after the onset of an ischemic event, when brain cells undergo swelling through cytotoxic edema. On the other hand, water diffusion is anisotropic in white matter, because axon membranes limit molecular movement perpendicularly to the fibers. This feature can be exploited to map out the orientation in space of the white matter tracks and image brain connections. More recently, it has been shown that diffusion MRI could accurately detect cortical activation. As the diffusion response precedes by several seconds the hemodynamic response captured by BOLD fMRI, it has been suggested that water diffusion could reflect early neuronal events, such as the transient swelling of activated cortical cells. If confirmed, this discovery will represent a significant breakthrough, allowing non invasive access to a direct physiological marker of brain activation. This approach will bridge the gap between invasive optical imaging techniques in neuronal cell cultures, and current functional neuroimaging approaches in humans, which are based on indirect and remote blood flow changes.

The Chomsky—Place correspondence 1993–1994

PubMed Central

Chomsky, Noam; Place, Ullin T.

2000-01-01

Edited correspondence between Ullin T. Place and Noam Chomsky, which occurred in 1993–1994, is presented. The principal topics are (a) deep versus surface structure; (b) computer modeling of the brain; (c) the evolutionary origins of language; (d) behaviorism; and (e) a dispositional account of language. This correspondence includes Chomsky's denial that he ever characterized deep structure as innate; Chomsky's critique of computer modeling (both traditional and connectionist) of the brain; Place's critique of Chomsky's alleged failure to provide an adequate account of the evolutionary origins of language, and Chomsky's response that such accounts are “pop-Darwinian fairy tales”; and Place's arguments for, and Chomsky's against, the relevance of behaviorism to linguistic theory, especially the relevance of a behavioral approach to language that is buttressed by a dispositional account of sentence construction. PMID:22477211

The Chomsky-Place correspondence 1993-1994.

PubMed

Chomsky, N; Place, U T

2000-01-01

Edited correspondence between Ullin T. Place and Noam Chomsky, which occurred in 1993-1994, is presented. The principal topics are (a) deep versus surface structure; (b) computer modeling of the brain; (c) the evolutionary origins of language; (d) behaviorism; and (e) a dispositional account of language. This correspondence includes Chomsky's denial that he ever characterized deep structure as innate; Chomsky's critique of computer modeling (both traditional and connectionist) of the brain; Place's critique of Chomsky's alleged failure to provide an adequate account of the evolutionary origins of language, and Chomsky's response that such accounts are "pop-Darwinian fairy tales"; and Place's arguments for, and Chomsky's against, the relevance of behaviorism to linguistic theory, especially the relevance of a behavioral approach to language that is buttressed by a dispositional account of sentence construction.

Acupuncture mobilizes the brain's default mode and its anti-correlated network in healthy subjects.

PubMed

Hui, Kathleen K S; Marina, Ovidiu; Claunch, Joshua D; Nixon, Erika E; Fang, Jiliang; Liu, Jing; Li, Ming; Napadow, Vitaly; Vangel, Mark; Makris, Nikos; Chan, Suk-Tak; Kwong, Kenneth K; Rosen, Bruce R

2009-09-01

Previous work has shown that acupuncture stimulation evokes deactivation of a limbic-paralimbic-neocortical network (LPNN) as well as activation of somatosensory brain regions. This study explores the activity and functional connectivity of these regions during acupuncture vs. tactile stimulation and vs. acupuncture associated with inadvertent sharp pain. Acupuncture during 201 scans and tactile stimulation during 74 scans for comparison at acupoints LI4, ST36 and LV3 was monitored with fMRI and psychophysical response in 48 healthy subjects. Clusters of deactivated regions in the medial prefrontal, medial parietal and medial temporal lobes as well as activated regions in the sensorimotor and a few paralimbic structures can be identified during acupuncture by general linear model analysis and seed-based cross correlation analysis. Importantly, these clusters showed virtual identity with the default mode network and the anti-correlated task-positive network in response to stimulation. In addition, the amygdala and hypothalamus, structures not routinely reported in the default mode literature, were frequently involved in acupuncture. When acupuncture induced sharp pain, the deactivation was attenuated or became activated instead. Tactile stimulation induced greater activation of the somatosensory regions but less extensive deactivation of the LPNN. These results indicate that the deactivation of the LPNN during acupuncture cannot be completely explained by the demand of attention that is commonly proposed in the default mode literature. Our results suggest that acupuncture mobilizes the anti-correlated functional networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response.

Forebrain Mechanisms of Nociception and Pain: Analysis through Imaging

NASA Astrophysics Data System (ADS)

Casey, Kenneth L.

1999-07-01

Pain is a unified experience composed of interacting discriminative, affective-motivational, and cognitive components, each of which is mediated and modulated through forebrain mechanisms acting at spinal, brainstem, and cerebral levels. The size of the human forebrain in relation to the spinal cord gives anatomical emphasis to forebrain control over nociceptive processing. Human forebrain pathology can cause pain without the activation of nociceptors. Functional imaging of the normal human brain with positron emission tomography (PET) shows synaptically induced increases in regional cerebral blood flow (rCBF) in several regions specifically during pain. We have examined the variables of gender, type of noxious stimulus, and the origin of nociceptive input as potential determinants of the pattern and intensity of rCBF responses. The structures most consistently activated across genders and during contact heat pain, cold pain, cutaneous laser pain or intramuscular pain were the contralateral insula and anterior cingulate cortex, the bilateral thalamus and premotor cortex, and the cerebellar vermis. These regions are commonly activated in PET studies of pain conducted by other investigators, and the intensity of the brain rCBF response correlates parametrically with perceived pain intensity. To complement the human studies, we developed an animal model for investigating stimulus-induced rCBF responses in the rat. In accord with behavioral measures and the results of human PET, there is a progressive and selective activation of somatosensory and limbic system structures in the brain and brainstem following the subcutaneous injection of formalin. The animal model and human PET studies should be mutually reinforcing and thus facilitate progress in understanding forebrain mechanisms of normal and pathological pain.

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

Manifold decoding for neural representations of face viewpoint and gaze direction using magnetoencephalographic data.

PubMed

Kuo, Po-Chih; Chen, Yong-Sheng; Chen, Li-Fen

2018-05-01

The main challenge in decoding neural representations lies in linking neural activity to representational content or abstract concepts. The transformation from a neural-based to a low-dimensional representation may hold the key to encoding perceptual processes in the human brain. In this study, we developed a novel model by which to represent two changeable features of faces: face viewpoint and gaze direction. These features are embedded in spatiotemporal brain activity derived from magnetoencephalographic data. Our decoding results demonstrate that face viewpoint and gaze direction can be represented by manifold structures constructed from brain responses in the bilateral occipital face area and right superior temporal sulcus, respectively. Our results also show that the superposition of brain activity in the manifold space reveals the viewpoints of faces as well as directions of gazes as perceived by the subject. The proposed manifold representation model provides a novel opportunity to gain further insight into the processing of information in the human brain. © 2018 Wiley Periodicals, Inc.

Functional imaging studies in cannabis users.

PubMed

Chang, Linda; Chronicle, Edward P

2007-10-01

Cannabis remains the most widely used illegal drug in the United States. This update examines the available literature on neuroimaging studies of the brains of cannabis users. The majority of studies examining the acute effects of delta-9-tetrahydrocannabinol (THC) administration used PET methods and concluded that administration of THC leads to increased activation in frontal and paralimbic regions and the cerebellum. These increases in activation are broadly consistent with the behavioral effects of the drug. Although there is only equivocal evidence that chronic cannabis use might result in structural brain changes, blood-oxygenation-level-dependent-fMRI studies in chronic users consistently show alterations, or neuroadaptation, in the activation of brain networks responsible for higher cognitive functions. It is not yet certain whether these changes are reversible with abstinence. Given the high prevalence of cannabis use among adolescents, studies are needed to evaluate whether cannabis use might affect the developing brain. Considerable further work, employing longitudinal designs, is also required to determine whether cannabis use causes permanent functional alterations in the brains of adults.

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.

Enhanced Brain Responses to Pain-Related Words in Chronic Back Pain Patients and Their Modulation by Current Pain.

PubMed

Ritter, Alexander; Franz, Marcel; Puta, Christian; Dietrich, Caroline; Miltner, Wolfgang H R; Weiss, Thomas

2016-08-10

Previous functional magnetic resonance imaging (fMRI) studies in healthy controls (HC) and pain-free migraine patients found activations to pain-related words in brain regions known to be activated while subjects experience pain. The aim of the present study was to identify neural activations induced by pain-related words in a sample of chronic back pain (CBP) patients experiencing current chronic pain compared to HC. In particular, we were interested in how current pain influences brain activations induced by pain-related adjectives. Subjects viewed pain-related, negative, positive, and neutral words; subjects were asked to generate mental images related to these words during fMRI scanning. Brain activation was compared between CBP patients and HC in response to the different word categories and examined in relation to current pain in CBP patients. Pain-related words vs. neutral words activated a network of brain regions including cingulate cortex and insula in subjects and patients. There was stronger activation in medial and dorsolateral prefrontal cortex (DLPFC) and anterior midcingulate cortex in CPB patients than in HC. The magnitude of activation for pain-related vs. negative words showed a negative linear relationship to CBP patients' current pain. Our findings confirm earlier observations showing that pain-related words activate brain networks similar to noxious stimulation. Importantly, CBP patients show even stronger activation of these structures while merely processing pain-related words. Current pain directly influences on this activation.

Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain.

PubMed

Zhang, Zhan-Chi; Luan, Feng; Xie, Chun-Yan; Geng, Dan-Dan; Wang, Yan-Yong; Ma, Jun

2015-06-01

In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.

Integration of Brain and Skull in Prenatal Mouse Models of Apert and Crouzon Syndromes

PubMed Central

Motch Perrine, Susan M.; Stecko, Tim; Neuberger, Thomas; Jabs, Ethylin W.; Ryan, Timothy M.; Richtsmeier, Joan T.

2017-01-01

The brain and skull represent a complex arrangement of integrated anatomical structures composed of various cell and tissue types that maintain structural and functional association throughout development. Morphological integration, a concept developed in vertebrate morphology and evolutionary biology, describes the coordinated variation of functionally and developmentally related traits of organisms. Syndromic craniosynostosis is characterized by distinctive changes in skull morphology and perceptible, though less well studied, changes in brain structure and morphology. Using mouse models for craniosynostosis conditions, our group has precisely defined how unique craniosynostosis causing mutations in fibroblast growth factor receptors affect brain and skull morphology and dysgenesis involving coordinated tissue-specific effects of these mutations. Here we examine integration of brain and skull in two mouse models for craniosynostosis: one carrying the FGFR2c C342Y mutation associated with Pfeiffer and Crouzon syndromes and a mouse model carrying the FGFR2 S252W mutation, one of two mutations responsible for two-thirds of Apert syndrome cases. Using linear distances estimated from three-dimensional coordinates of landmarks acquired from dual modality imaging of skull (high resolution micro-computed tomography and magnetic resonance microscopy) of mice at embryonic day 17.5, we confirm variation in brain and skull morphology in Fgfr2cC342Y/+ mice, Fgfr2+/S252W mice, and their unaffected littermates. Mutation-specific variation in neural and cranial tissue notwithstanding, patterns of integration of brain and skull differed only subtly between mice carrying either the FGFR2c C342Y or the FGFR2 S252W mutation and their unaffected littermates. However, statistically significant and substantial differences in morphological integration of brain and skull were revealed between the two mutant mouse models, each maintained on a different strain. Relative to the effects of disease-associated mutations, our results reveal a stronger influence of the background genome on patterns of brain-skull integration and suggest robust genetic, developmental, and evolutionary relationships between neural and skeletal tissues of the head. PMID:28790902

The distribution of pain activity across the human neonatal brain is sex dependent.

PubMed

Verriotis, Madeleine; Jones, Laura; Whitehead, Kimberley; Laudiano-Dray, Maria; Panayotidis, Ismini; Patel, Hemani; Meek, Judith; Fabrizi, Lorenzo; Fitzgerald, Maria

2018-05-12

In adults, there are differences between male and female structural and functional brain connectivity, specifically for those regions involved in pain processing. This may partly explain the observed sex differences in pain sensitivity, tolerance, and inhibitory control, and in the development of chronic pain. However, it is not known if these differences exist from birth. Cortical activity in response to a painful stimulus can be observed in the human neonatal brain, but this nociceptive activity continues to develop in the postnatal period and is qualitatively different from that of adults, partly due to the considerable cortical maturation during this time. This research aimed to investigate the effects of sex and prematurity on the magnitude and spatial distribution pattern of the long-latency nociceptive event-related potential (nERP) using electroencephalography (EEG). We measured the cortical response time-locked to a clinically required heel lance in 81 neonates born between 29 and 42 weeks gestational age (median postnatal age 4 days). The results show that heel lance results in a spatially widespread nERP response in the majority of newborns. Importantly, a widespread pattern is significantly more likely to occur in females, irrespective of gestational age at birth. This effect is not observed for the short latency somatosensory waveform in the same infants, indicating that it is selective for the nociceptive component of the response. These results suggest the early onset of a greater anatomical and functional connectivity reported in the adult female brain, and indicate the presence of pain-related sex differences from birth. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2007-01-01

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

The effects of musical training on structural brain development: a longitudinal study.

PubMed

Hyde, Krista L; Lerch, Jason; Norton, Andrea; Forgeard, Marie; Winner, Ellen; Evans, Alan C; Schlaug, Gottfried

2009-07-01

Long-term instrumental music training is an intense, multisensory and motor experience that offers an ideal opportunity to study structural brain plasticity in the developing brain in correlation with behavioral changes induced by training. Here, for the first time, we demonstrate structural brain changes after only 15 months of musical training in early childhood, which were correlated with improvements in musically relevant motor and auditory skills. These findings shed light on brain plasticity, and suggest that structural brain differences in adult experts (whether musicians or experts in other areas) are likely due to training-induced brain plasticity.

Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction

PubMed Central

Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Parvaz, Muhammad A.; Alia-Klein, Nelly; Volkow, Nora D.; Goldstein, Rita Z.

2012-01-01

Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) which was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. PMID:22775285

Drawing on the right side of the brain: a voxel-based morphometry analysis of observational drawing.

PubMed

Chamberlain, Rebecca; McManus, I Chris; Brunswick, Nicola; Rankin, Qona; Riley, Howard; Kanai, Ryota

2014-08-01

Structural brain differences in relation to expertise have been demonstrated in a number of domains including visual perception, spatial navigation, complex motor skills and musical ability. However no studies have assessed the structural differences associated with representational skills in visual art. As training artists are inclined to be a heterogeneous group in terms of their subject matter and chosen media, it was of interest to investigate whether there would be any consistent changes in neural structure in response to increasing representational drawing skill. In the current study a cohort of 44 graduate and post-graduate art students and non-art students completed drawing tasks. Scores on these tasks were then correlated with the regional grey and white matter volume in cortical and subcortical structures. An increase in grey matter density in the left anterior cerebellum and the right medial frontal gyrus was observed in relation to observational drawing ability, whereas artistic training (art students vs. non-art students) was correlated with increased grey matter density in the right precuneus. This suggests that observational drawing ability relates to changes in structures pertaining to fine motor control and procedural memory, and that artistic training in addition is associated with enhancement of structures pertaining to visual imagery. The findings corroborate the findings of small-scale fMRI studies and provide insights into the properties of the developing artistic brain. Copyright © 2014 Elsevier Inc. All rights reserved.

Wavelet multiresolution complex network for decoding brain fatigued behavior from P300 signals

NASA Astrophysics Data System (ADS)

Gao, Zhong-Ke; Wang, Zi-Bo; Yang, Yu-Xuan; Li, Shan; Dang, Wei-Dong; Mao, Xiao-Qian

2018-09-01

Brain-computer interface (BCI) enables users to interact with the environment without relying on neural pathways and muscles. P300 based BCI systems have been extensively used to achieve human-machine interaction. However, the appearance of fatigue symptoms during operation process leads to the decline in classification accuracy of P300. Characterizing brain cognitive process underlying normal and fatigue conditions constitutes a problem of vital importance in the field of brain science. We in this paper propose a novel wavelet decomposition based complex network method to efficiently analyze the P300 signals recorded in the image stimulus test based on classical 'Oddball' paradigm. Initially, multichannel EEG signals are decomposed into wavelet coefficient series. Then we construct complex network by treating electrodes as nodes and determining the connections according to the 2-norm distances between wavelet coefficient series. The analysis of topological structure and statistical index indicates that the properties of brain network demonstrate significant distinctions between normal status and fatigue status. More specifically, the brain network reconfiguration in response to the cognitive task in fatigue status is reflected as the enhancement of the small-worldness.

A close look at brain dynamics: cells and vessels seen by in vivo two-photon microscopy.

PubMed

Fumagalli, Stefano; Ortolano, Fabrizio; De Simoni, Maria-Grazia

2014-10-01

The cerebral vasculature has a unique role in providing a constant supply of oxygen and nutrients to ensure normal brain functions. Blood vessels that feed the brain are far from being simply channels for passive transportation of fluids. They form complex structures made up of different cell types. These structures regulate blood supply, local concentrations of O2 and CO2, transport of small molecules, trafficking of plasma cells and fine cerebral functions in normal and diseased brains. Until few years ago, analysis of these functions has been typically based on post mortem techniques, whose interpretation is limited by the need for tissue processing at specific times. For a reliable and effective picture of the dynamic processes in the central nervous system, real-time information in vivo is required. There are now few in vivo systems, among which two-photon microscopy (2-PM) is a truly innovative tool for studying the brain. 2-PM has been used to dissect specific aspects of vascular and immune cell dynamics in the context of neurological diseases, providing exciting results that could not have been obtained with conventional methods. This review summarizes the latest findings on vascular and immune system action in the brain, with particular focus on the dynamic responses after ischemic brain injury. 2-PM has helped define the hierarchical architecture of the brain vasculature, the dynamic interaction between the vasculature and immune cells recruited to lesion sites, the effects of blood flow on neuronal and microglial activity and the ability of cells of the neurovascular unit to regulate blood flow. Copyright © 2014 Elsevier Ltd. All rights reserved.

Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders.

PubMed

Iturria-Medina, Yasser; Sotero, Roberto C; Toussaint, Paule J; Evans, Alan C

2014-11-01

Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders.

Epidemic Spreading Model to Characterize Misfolded Proteins Propagation in Aging and Associated Neurodegenerative Disorders

PubMed Central

Iturria-Medina, Yasser; Sotero, Roberto C.; Toussaint, Paule J.; Evans, Alan C.

2014-01-01

Misfolded proteins (MP) are a key component in aging and associated neurodegenerative disorders. For example, misfolded Amyloid-ß (Aß) and tau proteins are two neuropathogenic hallmarks of Alzheimer's disease. Mechanisms underlying intra-brain MP propagation/deposition remain essentially uncharacterized. Here, is introduced an epidemic spreading model (ESM) for MP dynamics that considers propagation-like interactions between MP agents and the brain's clearance response across the structural connectome. The ESM reproduces advanced Aß deposition patterns in the human brain (explaining 46∼56% of the variance in regional Aß loads, in 733 subjects from the ADNI database). Furthermore, this model strongly supports a) the leading role of Aß clearance deficiency and early Aß onset age during Alzheimer's disease progression, b) that effective anatomical distance from Aß outbreak region explains regional Aß arrival time and Aß deposition likelihood, c) the multi-factorial impact of APOE e4 genotype, gender and educational level on lifetime intra-brain Aß propagation, and d) the modulatory impact of Aß propagation history on tau proteins concentrations, supporting the hypothesis of an interrelated pathway between Aß pathophysiology and tauopathy. To our knowledge, the ESM is the first computational model highlighting the direct link between structural brain networks, production/clearance of pathogenic proteins and associated intercellular transfer mechanisms, individual genetic/demographic properties and clinical states in health and disease. In sum, the proposed ESM constitutes a promising framework to clarify intra-brain region to region transference mechanisms associated with aging and neurodegenerative disorders. PMID:25412207

Unveiling the development of intracranial injury using dynamic brain EIT: an evaluation of current reconstruction algorithms.

PubMed

Li, Haoting; Chen, Rongqing; Xu, Canhua; Liu, Benyuan; Tang, Mengxing; Yang, Lin; Dong, Xiuzhen; Fu, Feng

2017-08-21

Dynamic brain electrical impedance tomography (EIT) is a promising technique for continuously monitoring the development of cerebral injury. While there are many reconstruction algorithms available for brain EIT, there is still a lack of study to compare their performance in the context of dynamic brain monitoring. To address this problem, we develop a framework for evaluating different current algorithms with their ability to correctly identify small intracranial conductivity changes. Firstly, a simulation 3D head phantom with realistic layered structure and impedance distribution is developed. Next several reconstructing algorithms, such as back projection (BP), damped least-square (DLS), Bayesian, split Bregman (SB) and GREIT are introduced. We investigate their temporal response, noise performance, location and shape error with respect to different noise levels on the simulation phantom. The results show that the SB algorithm demonstrates superior performance in reducing image error. To further improve the location accuracy, we optimize SB by incorporating the brain structure-based conductivity distribution priors, in which differences of the conductivities between different brain tissues and the inhomogeneous conductivity distribution of the skull are considered. We compare this novel algorithm (called SB-IBCD) with SB and DLS using anatomically correct head shaped phantoms with spatial varying skull conductivity. Main results and Significance: The results showed that SB-IBCD is the most effective in unveiling small intracranial conductivity changes, where it can reduce the image error by an average of 30.0% compared to DLS.

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.

Asymmetry of Hemispheric Network Topology Reveals Dissociable Processes between Functional and Structural Brain Connectome in Community-Living Elders

PubMed Central

Sun, Yu; Li, Junhua; Suckling, John; Feng, Lei

2017-01-01

Human brain is structurally and functionally asymmetrical and the asymmetries of brain phenotypes have been shown to change in normal aging. Recent advances in graph theoretical analysis have showed topological lateralization between hemispheric networks in the human brain throughout the lifespan. Nevertheless, apparent discrepancies of hemispheric asymmetry were reported between the structural and functional brain networks, indicating the potentially complex asymmetry patterns between structural and functional networks in aging population. In this study, using multimodal neuroimaging (resting-state fMRI and structural diffusion tensor imaging), we investigated the characteristics of hemispheric network topology in 76 (male/female = 15/61, age = 70.08 ± 5.30 years) community-dwelling older adults. Hemispheric functional and structural brain networks were obtained for each participant. Graph theoretical approaches were then employed to estimate the hemispheric topological properties. We found that the optimal small-world properties were preserved in both structural and functional hemispheric networks in older adults. Moreover, a leftward asymmetry in both global and local levels were observed in structural brain networks in comparison with a symmetric pattern in functional brain network, suggesting a dissociable process of hemispheric asymmetry between structural and functional connectome in healthy older adults. Finally, the scores of hemispheric asymmetry in both structural and functional networks were associated with behavioral performance in various cognitive domains. Taken together, these findings provide new insights into the lateralized nature of multimodal brain connectivity, highlight the potentially complex relationship between structural and functional brain network alterations, and augment our understanding of asymmetric structural and functional specializations in normal aging. PMID:29209197

Validation of clay modeling as a learning tool for the periventricular structures of the human brain.

PubMed

Akle, Veronica; Peña-Silva, Ricardo A; Valencia, Diego M; Rincón-Perez, Carlos W

2018-03-01

Visualizing anatomical structures and functional processes in three dimensions (3D) are important skills for medical students. However, contemplating 3D structures mentally and interpreting biomedical images can be challenging. This study examines the impact of a new pedagogical approach to teaching neuroanatomy, specifically how building a 3D-model from oil-based modeling clay affects learners' understanding of periventricular structures of the brain among undergraduate medical students in Colombia. Students were provided with an instructional video before building the models of the structures, and thereafter took a computer-based quiz. They then brought their clay models to class where they answered questions about the structures via interactive response cards. Their knowledge of periventricular structures was assessed with a paper-based quiz. Afterward, a focus group was conducted and a survey was distributed to understand students' perceptions of the activity, as well as the impact of the intervention on their understanding of anatomical structures in 3D. Quiz scores of students that constructed the models were significantly higher than those taught the material in a more traditional manner (P < 0.05). Moreover, the modeling activity reduced time spent studying the topic and increased understanding of spatial relationships between structures in the brain. The results demonstrated a significant difference between genders in their self-perception of their ability to contemplate and rotate structures mentally (P < 0.05). The study demonstrated that the construction of 3D clay models in combination with autonomous learning activities was a valuable and efficient learning tool in the anatomy course, and that additional models could be designed to promote deeper learning of other neuroanatomy topics. Anat Sci Educ 11: 137-145. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

Neural responses to nostalgia-evoking music modeled by elements of dynamic musical structure and individual differences in affective traits.

PubMed

Barrett, Frederick S; Janata, Petr

2016-10-01

Nostalgia is an emotion that is most commonly associated with personally and socially relevant memories. It is primarily positive in valence and is readily evoked by music. It is also an idiosyncratic experience that varies between individuals based on affective traits. We identified frontal, limbic, paralimbic, and midbrain brain regions in which the strength of the relationship between ratings of nostalgia evoked by music and blood-oxygen-level-dependent (BOLD) signal was predicted by affective personality measures (nostalgia proneness and the sadness scale of the Affective Neuroscience Personality Scales) that are known to modulate the strength of nostalgic experiences. We also identified brain areas including the inferior frontal gyrus, substantia nigra, cerebellum, and insula in which time-varying BOLD activity correlated more strongly with the time-varying tonal structure of nostalgia-evoking music than with music that evoked no or little nostalgia. These findings illustrate one way in which the reward and emotion regulation networks of the brain are recruited during the experiencing of complex emotional experiences triggered by music. These findings also highlight the importance of considering individual differences when examining the neural responses to strong and idiosyncratic emotional experiences. Finally, these findings provide a further demonstration of the use of time-varying stimulus-specific information in the investigation of music-evoked experiences. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Research advances on cortical functional and structural deficits of amblyopia].

PubMed

Wu, Y; Liu, L Q

2017-05-11

Previous studies have observed functional deficits in primary visual cortex. With the development of functional magnetic resonance imaging and electrophysiological technique, the research of the striate, extra-striate cortex and higher-order cortical deficit underlying amblyopia reaches a new stage. The neural mechanisms of amblyopia show that anomalous responses exist throughout the visual processing hierarchy, including the functional and structural abnormalities. This review aims to summarize the current knowledge about structural and functional deficits of brain regions associated with amblyopia. (Chin J Ophthalmol, 2017, 53: 392 - 395) .

Vocal parameters that indicate threat level correlate with FOS immunolabeling in social and vocal control brain regions.

PubMed

Ellis, Jesse M S; Riters, Lauren V

2012-01-01

Transmitting information via communicative signals is integral to interacting with conspecifics, and some species achieve this task by varying vocalizations to reflect context. Although signal variation is critical to social interactions, the underlying neural control has not been studied. In response to a predator, black-capped chickadees (Poecile atricapilla) produce mobbing calls (chick-a-dee calls) with various parameters, some of which convey information about the threat stimulus. We predicted that vocal parameters indicative of threat would be associated with distinct patterns of neuronal activity within brain areas involved in social behavior and those involved in the sensorimotor control of vocal production. To test this prediction, we measured the syntax and structural aspects of chick-a-dee call production in response to a hawk model and assessed the protein product of the immediate early gene FOS in brain regions implicated in context-specific vocal and social behavior. These regions include the medial preoptic area (POM) and lateral septum (LS), as well as regions involved in vocal motor control, including the dorsomedial nucleus of the intercollicular complex and the HVC. We found correlations linking call rate (previously demonstrated to reflect threat) to labeling in the POM and LS. Labeling in the HVC correlated with the number of D notes per call, which may also signal threat level. Labeling in the call control region dorsomedial nucleus was associated with the structure of D notes and the overall number of notes, but not call rate or type of notes produced. These results suggest that the POM and LS may influence attributes of vocalizations produced in response to predators and that the brain region implicated in song control, the HVC, also influences call production. Because variation in chick-a-dee call rate indicates predator threat, we speculate that these areas could integrate with motor control regions to imbue mobbing signals with additional information about threat level. Copyright © 2011 S. Karger AG, Basel.

The expression of interleukin-6 and its receptor in various brain regions and their roles in exploratory behavior and stress responses.

PubMed

Aniszewska, A; Chłodzińska, N; Bartkowska, K; Winnicka, M M; Turlejski, K; Djavadian, R L

2015-07-15

We examined the involvement of interleukin-6 (IL-6) and its receptor IL-6Rα on behavior and stress responses in mice. In the open field, both wild-type (WT) and IL-6 deficient mice displayed similar levels of locomotor activity; however, IL-6 deficient mice spent more time in the central part of the arena compared to control WT mice. After behavioral testing, mice were subjected to stress and then sacrificed. The levels of IL-6 and its receptor in their brains were determined. Immunohistochemical labeling of brain sections for IL-6 showed a high level of expression in the subventricular zone of the lateral ventricles and in the border zone of the third and fourth ventricles. Interestingly, 95% of the IL-6-expressing cells had an astrocytic phenotype, and the remaining 5% were microglial cells. A low level of IL-6 expression was observed in the olfactory bulb, hypothalamus, hippocampus, cerebral cortex, cerebellum, midbrain and several brainstem structures. The vast majority of IL-6-expressing cells in these structures had a neuronal phenotype. Stress increased the number of IL-6-immunoreactive astrocytes and microglial cells. The levels of the IL-6Rα receptor were increased in the hypothalamus of stressed mice. Therefore, in this study, we describe for the first time the distribution of IL-6 in various types of brain cells and in previously unreported regions, such as the subventricular zone of the lateral ventricle. Moreover, we provide data on regional distribution and expression within specific cell phenotypes. This highly differential expression of IL-6 indicates its specific roles in the regulation of neuronal and astrocytic functions, in addition to the roles of IL-6 and its receptor IL-6Rα in stress responses. Copyright © 2015 Elsevier B.V. All rights reserved.

Theoretical Frameworks and Mechanistic Aspects of Alcohol Addiction: Alcohol Addiction as a Reward Deficit Disorder

PubMed Central

2012-01-01

Alcoholism can be defined by a compulsion to seek and take drug, loss of control in limiting intake, and the emergence of a negative emotional state when access to the drug is prevented. Alcoholism impacts multiple motivational mechanisms and can be conceptualized as a disorder that includes a progression from impulsivity (positive reinforcement) to compulsivity (negative reinforcement). The compulsive drug seeking associated with alcoholism can be derived from multiple neuroadaptations, but the thesis argued here is that a key component involves the construct of negative reinforcement. Negative reinforcement is defined as drug taking that alleviates a negative emotional state. The negative emotional state that drives such negative reinforcement is hypothesized to derive from dysregulation of specific neurochemical elements involved in reward and stress within the basal forebrain structures involving the ventral striatum and extended amygdala, respectively. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission, such as decreased dopamine and γ-aminobutyric acid function in the ventral striatum, but also recruitment of brain stress systems, such as corticotropin-releasing factor (CRF), in the extended amygdala. Acute withdrawal from chronic alcohol, sufficient to produce dependence, increases reward thresholds, increases anxiety-like responses, decreases dopamine system function, and increases extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists also block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence, and to contribute to the compulsivity of alcoholism. Other components of brain stress systems in the extended amygdala that interact with CRF and that may contribute to the negative motivational state of withdrawal include norepinephrine, dynorphin, and neuropeptide Y. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for a negative emotional state that is responsible for the negative reinforcement driving, at least partially, the compulsivity of alcoholism. PMID:21744309

Distinct sensory representations of wind and near-field sound in the Drosophila brain

PubMed Central

Yorozu, Suzuko; Wong, Allan; Fischer, Brian J.; Dankert, Heiko; Kernan, Maurice J.; Kamikouchi, Azusa; Ito, Kei; Anderson, David J.

2009-01-01

Behavioral responses to wind are thought to play a critical role in controlling the dispersal and population genetics of wild Drosophila species1,2, as well as their navigation in flight3, but their underlying neurobiological basis is unknown. We show that Drosophila melanogaster, like wild-caught Drosophila strains4, exhibits robust wind-induced suppression of locomotion (WISL), in response to air currents delivered at speeds normally encountered in nature1,2. Here we identify wind-sensitive neurons in Johnston’s Organ (JO), an antennal mechanosensory structure previously implicated in near-field sound detection (reviewed in5,6). Using Gal4 lines targeted to different subsets of JO neurons7, and a genetically encoded calcium indicator8, we show that wind and near-field sound (courtship song) activate distinct populations of JO neurons, which project to different regions of the antennal and mechanosensory motor center (AMMC) in the central brain. Selective genetic ablation of wind-sensitive JO neurons in the antenna abolishes WISL behavior, without impairing hearing. Different neuronal subsets within the wind-sensitive population, moreover, respond to different directions of arista deflection caused by airflow and project to different regions of the AMMC, providing a rudimentary map of wind-direction in the brain. Importantly, sound- and wind-sensitive JO neurons exhibit different intrinsic response properties: the former are phasically activated by small, bi-directional, displacements of the aristae, while the latter are tonically activated by unidirectional, static deflections of larger magnitude. These different intrinsic properties are well suited to the detection of oscillatory pulses of near-field sound and laminar airflow, respectively. These data identify wind-sensitive neurons in JO, a structure that has been primarily associated with hearing, and reveal how the brain can distinguish different types of air particle movements, using a common sensory organ. PMID:19279637

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.…

A Discordant Monozygotic Twin Design Shows Blunted Cortisol Reactivity among Bullied Children

ERIC Educational Resources Information Center

Ouellet-Morin, Isabelle; Danese, Andrea; Bowes, Lucy; Shakoor, Sania; Ambler, Antony; Pariante, Carmine M.; Papadopoulos, Andrew S.; Caspi, Avshalom; Moffitt, Terrie E.; Arseneault, Louise

2011-01-01

Objective: Childhood adverse experiences are known to engender persistent changes in stress-related systems and brain structures involved in mood, cognition, and behavior in animal models. Uncertainty remains about the causal effect of early stressful experiences on physiological response to stress in human beings, as the impact of these…

ALCOHOL AND THE PREFRONTAL CORTEX

PubMed Central

Abernathy, Kenneth; Chandler, L. Judson; Woodward, John J.

2013-01-01

The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the mammalian brain. Its major role is to integrate and interpret inputs from cortical and sub-cortical structures and use this information to develop purposeful responses that reflect both present and future circumstances. This includes both action-oriented sequences involved in obtaining rewards and inhibition of behaviors that pose undue risk or harm to the individual. Given the central role in initiating and regulating these often complex cognitive and behavioral responses, it is no surprise that alcohol has profound effects on the function of the prefrontal cortex. In this chapter, we review the basic anatomy and physiology of the prefrontal cortex and discuss what is known about the actions of alcohol on the function of this brain region. This includes a review of both the human and animal literature including information on the electrophysiological and behavioral effects that follow acute and chronic exposure to alcohol. The chapter concludes with a discussion of unanswered questions and areas needing further investigation. PMID:20813246

Brain Signals of Face Processing as Revealed by Event-Related Potentials

PubMed Central

Olivares, Ela I.; Iglesias, Jaime; Saavedra, Cristina; Trujillo-Barreto, Nelson J.; Valdés-Sosa, Mitchell

2015-01-01

We analyze the functional significance of different event-related potentials (ERPs) as electrophysiological indices of face perception and face recognition, according to cognitive and neurofunctional models of face processing. Initially, the processing of faces seems to be supported by early extrastriate occipital cortices and revealed by modulations of the occipital P1. This early response is thought to reflect the detection of certain primary structural aspects indicating the presence grosso modo of a face within the visual field. The posterior-temporal N170 is more sensitive to the detection of faces as complex-structured stimuli and, therefore, to the presence of its distinctive organizational characteristics prior to within-category identification. In turn, the relatively late and probably more rostrally generated N250r and N400-like responses might respectively indicate processes of access and retrieval of face-related information, which is stored in long-term memory (LTM). New methods of analysis of electrophysiological and neuroanatomical data, namely, dynamic causal modeling, single-trial and time-frequency analyses, are highly recommended to advance in the knowledge of those brain mechanisms concerning face processing. PMID:26160999

Differential electrophysiological signatures of semantic and syntactic scene processing.

PubMed

Võ, Melissa L-H; Wolfe, Jeremy M

2013-09-01

In sentence processing, semantic and syntactic violations elicit differential brain responses observable in event-related potentials: An N400 signals semantic violations, whereas a P600 marks inconsistent syntactic structure. Does the brain register similar distinctions in scene perception? To address this question, we presented participants with semantic inconsistencies, in which an object was incongruent with a scene's meaning, and syntactic inconsistencies, in which an object violated structural rules. We found a clear dissociation between semantic and syntactic processing: Semantic inconsistencies produced negative deflections in the N300-N400 time window, whereas mild syntactic inconsistencies elicited a late positivity resembling the P600 found for syntactic inconsistencies in sentence processing. Extreme syntactic violations, such as a hovering beer bottle defying gravity, were associated with earlier perceptual processing difficulties reflected in the N300 response, but failed to produce a P600 effect. We therefore conclude that different neural populations are active during semantic and syntactic processing of scenes, and that syntactically impossible object placements are processed in a categorically different manner than are syntactically resolvable object misplacements.

Attack of the nervous system by Clostridium perfringens Epsilon toxin: from disease to mode of action on neural cells.

PubMed

Wioland, Laetitia; Dupont, Jean-Luc; Bossu, Jean-Louis; Popoff, Michel R; Poulain, Bernard

2013-12-01

Epsilon toxin (ET), produced by Clostridium perfringens types B and D, ranks among the four most potent poisonous substances known so far. ET-intoxication is responsible for enterotoxaemia in animals, mainly sheep and goats. This disease comprises several manifestations indicating the attack of the nervous system. This review aims to summarize the effects of ET on central nervous system. ET binds to endothelial cells of brain capillary vessels before passing through the blood-brain barrier. Therefore, it induces perivascular oedema and accumulates into brain. ET binding to different brain structures and to different component in the brain indicates regional susceptibility to the toxin. Histological examination has revealed nerve tissue and cellular lesions, which may be directly or indirectly caused by ET. The naturally occurring disease caused by ET-intoxication can be reproduced experimentally in rodents. In mice and rats, ET recognizes receptor at the surface of different neural cell types, including certain neurons (e.g. the granule cells in cerebellum) as well as oligodendrocytes, which are the glial cells responsible for the axons myelination. Moreover, ET induces release of glutamate and other transmitters, leading to firing of neural network. The precise mode of action of ET on neural cells remains to be determined. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Research Review: Neural response to threat in children, adolescents, and adults after child maltreatment - a quantitative meta-analysis.

PubMed

Hein, Tyler C; Monk, Christopher S

2017-03-01

Child maltreatment is common and has long-term consequences for affective function. Investigations of neural consequences of maltreatment have focused on the amygdala. However, developmental neuroscience indicates that other brain regions are also likely to be affected by child maltreatment, particularly in the social information processing network (SIPN). We conducted a quantitative meta-analysis to: confirm that maltreatment is related to greater bilateral amygdala activation in a large sample that was pooled across studies; investigate other SIPN structures that are likely candidates for altered function; and conduct a data-driven examination to identify additional regions that show altered activation in maltreated children, teens, and adults. We conducted an activation likelihood estimation analysis with 1,733 participants across 20 studies of emotion processing in maltreated individuals. Maltreatment is associated with increased bilateral amygdala activation to emotional faces. One SIPN structure is altered: superior temporal gyrus, of the detection node, is hyperactive in maltreated individuals. The results of the whole-brain corrected analysis also show hyperactivation of the parahippocampal gyrus and insula in maltreated individuals. The meta-analysis confirms that maltreatment is related to increased bilateral amygdala reactivity and also shows that maltreatment affects multiple additional structures in the brain that have received little attention in the literature. Thus, although the majority of studies examining maltreatment and brain function have focused on the amygdala, these findings indicate that the neural consequences of child maltreatment involve a broader network of structures. © 2016 Association for Child and Adolescent Mental Health.

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

PubMed

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

2017-08-01

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

[Clinical-pathogenetic features of meningococcal infection in children].

PubMed

Buriak, V N; Serhyenko, A S

2011-01-01

Analysis features of clinical manifestation and pathogenetic mechanisms of development of meningococcal infection is introduced. It is emphasized that in most cases mentioned infection is characterized by mild course as nasopharyngitidis. However relatively seldom developing generalize form put this phatology on third place after intestinal infections and septicemia in structure of child mortality from infection deseases. Occurence of generalize forms of meningococcal infection depend on peculiarity of immune response is followed by release of endotoxin and exotoxin in blood stream. This toxins start up pathogenetic mechanisms, which lead to toxic shock, adrenal glands hemorrhage, brain edema, brain stem wedge in big occipital foramen.

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

PubMed Central

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

2013-01-01

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

Diffuse optical systems and methods to image physiological changes of the brain in response to focal TBI (Conference Presentation)

NASA Astrophysics Data System (ADS)

Abookasis, David; Volkov, Boris; Kofman, Itamar

2017-02-01

During the last four decades, various optical techniques have been proposed and intensively used for biomedical diagnosis and therapy both in animal model and in human. These techniques have several advantages over the traditional existing methods: simplicity in structure, low-cost, easy to handle, portable, can be used repeatedly over time near the patient bedside for continues monitoring, and offer high spatiotemporal resolution. In this work, we demonstrate the use of two optical imaging modalities namely, spatially modulated illumination and dual-wavelength laser speckle to image the changes in brain tissue chromophores, morphology, and metabolic before, during, and after the onset of focal traumatic brain injury in intact mouse head (n=15). Injury was applied in anesthetized mice by weight-drop apparatus using 50gram metal rod striking the mouse's head. Following data analysis, we show a series of hemodynamic and structural changes over time including higher deoxyhemoglobin, reduction in oxygen saturation and blood flow, cell swelling, etc., in comparison with baseline measurements. In addition, to validate the monitoring of cerebral blood flow by the imaging system, measurements with laser Doppler flowmetry were also performed (n=5), which confirmed reduction in blood flow following injury. Overall, our result demonstrates the capability of diffuse optical modalities to monitor and map brain tissue optical and physiological properties following brain trauma.

The nicotinic receptor blocker hexamethonium alters neuronal responses to glutamate in the medial septal area of the brain of the ground squirrel in vitro.

PubMed

Karavaev, E N; Popova, I Yu; Kichigina, V F

2008-03-01

Despite extensive interest in studies of the medial septal area, the nature of the interactions of its various neurochemical systems remains largely unclear. The aim of the present work was to clarify the role of nicotinic receptors in mediating the interaction of the glutamatergic and cholinergic systems in this structure. Extracellular recording of neuron activity in living slices of ground squirrel brain was used to study the influences of L-glutamate (1 microM) during application of the nicotinic receptor blocker hexamethonium (1 mM). The responses of septal neurons to glutamate depended on the type of their initial activity and the presence of pacemaker properties. This study is the first to show that glutamate increases the frequency of volleys in rhythmic neurons in the septum. Hexamethonium induced changes in neuron activity similar to the influences of glutamate. After prior application of hexamethonium, the responses of neurons to glutamate changed: activatory responses were masked and inhibitory responses were enhanced. Cholinergic modulation of the responses of septal neurons to glutamate were shown to occur, as did modulation of the strength of the oscillatory properties of the septal network by nicotinic receptors.

Random Forest Segregation of Drug Responses May Define Regions of Biological Significance.

PubMed

Bukhari, Qasim; Borsook, David; Rudin, Markus; Becerra, Lino

2016-01-01

The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF) method to detect differences in the pharmacological MRI (phMRI) response in rats to treatment with an analgesic drug (buprenorphine) as compared to control (saline). Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD), and high dose (HD), and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups. RF analysis was able to identify drug effects based on differential phMRI responses in the hippocampus, amygdala, nucleus accumbens, superior colliculus, and the lateral and posterior thalamus for drug vs. saline. These structures have high levels of mu opioid receptors. In addition these regions are involved in aversive signaling, which is inhibited by mu opioids. The results demonstrate that buprenorphine mediated phMRI responses comprise characteristic features that allow a supervised differentiation from placebo treated rats as well as the proper allocation to the respective drug dose group using the RF method, a method that has been successfully applied in clinical studies.

Noninvasive photoacoustic computed tomography of mouse brain metabolism in vivo

NASA Astrophysics Data System (ADS)

Yao, Junjie; Xia, Jun; Maslov, Konstantin; Avanaki, Mohammadreza R. N.; Tsytsarev, Vassiliy; Demchenko, Alexei V.; Wang, Lihong V.

2013-03-01

To control the overall action of the body, brain consumes a large amount of energy in proportion to its volume. In humans and many other species, the brain gets most of its energy from oxygen-dependent metabolism of glucose. An abnormal metabolic rate of glucose and/or oxygen usually reflects a diseased status of brain, such as cancer or Alzheimer's disease. We have demonstrated the feasibility of imaging mouse brain metabolism using photoacoustic computed tomography (PACT), a fast, noninvasive and functional imaging modality with optical contrast and acoustic resolution. Brain responses to forepaw stimulations were imaged transdermally and transcranially. 2-NBDG, which diffuses well across the blood-brain-barrier, provided exogenous contrast for photoacoustic imaging of glucose response. Concurrently, hemoglobin provided endogenous contrast for photoacoustic imaging of hemodynamic response. Glucose and hemodynamic responses were quantitatively unmixed by using two-wavelength measurements. We found that glucose uptake and blood perfusion around the somatosensory region of the contralateral hemisphere were both increased by stimulations, indicating elevated neuron activity. The glucose response amplitude was about half that of the hemodynamic response. While the glucose response area was more homogenous and confined within the somatosensory region, the hemodynamic response area showed a clear vascular pattern and spread about twice as wide as that of the glucose response. The PACT of mouse brain metabolism was validated by high-resolution open-scalp OR-PAM and fluorescence imaging. Our results demonstrate that 2-NBDG-enhanced PACT is a promising tool for noninvasive studies of brain metabolism.

Tractography patterns of subthalamic nucleus deep brain stimulation.

PubMed

Vanegas-Arroyave, Nora; Lauro, Peter M; Huang, Ling; Hallett, Mark; Horovitz, Silvina G; Zaghloul, Kareem A; Lungu, Codrin

2016-04-01

Deep brain stimulation therapy is an effective symptomatic treatment for Parkinson's disease, yet the precise mechanisms responsible for its therapeutic effects remain unclear. Although the targets of deep brain stimulation are grey matter structures, axonal modulation is known to play an important role in deep brain stimulation's therapeutic mechanism. Several white matter structures in proximity to the subthalamic nucleus have been implicated in the clinical benefits of deep brain stimulation for Parkinson's disease. We assessed the connectivity patterns that characterize clinically beneficial electrodes in Parkinson's disease patients, after deep brain stimulation of the subthalamic nucleus. We evaluated 22 patients with Parkinson's disease (11 females, age 57 ± 9.1 years, disease duration 13.3 ± 6.3 years) who received bilateral deep brain stimulation of the subthalamic nucleus at the National Institutes of Health. During an initial electrode screening session, one month after deep brain stimulation implantation, the clinical benefits of each contact were determined. The electrode was localized by coregistering preoperative magnetic resonance imaging and postoperative computer tomography images and the volume of tissue activated was estimated from stimulation voltage and impedance. Brain connectivity for the volume of tissue activated of deep brain stimulation contacts was assessed using probabilistic tractography with diffusion-tensor data. Areas most frequently connected to clinically effective contacts included the thalamus, substantia nigra, brainstem and superior frontal gyrus. A series of discriminant analyses demonstrated that the strength of connectivity to the superior frontal gyrus and the thalamus were positively associated with clinical effectiveness. The connectivity patterns observed in our study suggest that the modulation of white matter tracts directed to the superior frontal gyrus and the thalamus is associated with favourable clinical outcomes and may contribute to the therapeutic effects of deep brain stimulation. Our method can be further developed to reliably identify effective deep brain stimulation contacts and aid in the programming process. © 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.

Outlier Responses Reflect Sensitivity to Statistical Structure in the Human Brain

PubMed Central

Garrido, Marta I.

2013-01-01

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

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

PubMed

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

2008-07-09

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

The effect of family therapy on the changes in the severity of on-line game play and brain activity in adolescents with on-line game addiction.

PubMed

Han, Doug Hyun; Kim, Sun Mi; Lee, Young Sik; Renshaw, Perry F

2012-05-31

We evaluated whether a brief 3-week family therapy intervention would change patterns of brain activation in response to affection and gaming cues in adolescents from dysfunctional families who met criteria for on-line game addiction. Fifteen adolescents with on-line game addiction and fifteen adolescents without problematic on-line game play and an intact family structure were recruited. Over 3 weeks, families were asked to carry out homework assignments focused on increasing family cohesion for more than 1 hour/day and 4 days/week. Before therapy, adolescents with on-line game addiction demonstrated decreased activity as measured by functional magnetic resonance imaging (fMRI) within the caudate, middle temporal gyrus, and occipital lobe in response to images depicting parental affection and increased activity of the middle frontal and inferior parietal in response scenes from on-line games, relative to healthy comparison subjects. Improvement in perceived family cohesion following 3 weeks of treatment was associated with an increase in the activity of the caudate nucleus in response to affection stimuli and was inversely correlated with changes in on-line game playing time. With evidence of brain activation changes in response to on-line game playing cues and images depicting parental love, the present findings suggest that family cohesion may be an important factor in the treatment of problematic on-line game playing. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

The effect of family therapy on the changes in the severity of on-line game play and brain activity in adolescents with on-line game addiction

PubMed Central

Han, Doug Hyun; Kim, Sun Mi; Lee, Young Sik; Renshaw, Perry F.

2015-01-01

We evaluated whether a brief 3-week family therapy intervention would change patterns of brain activation in response to affection and gaming cues in adolescents from dysfunctional families who met criteria for on-line game addiction. Fifteen adolescents with on-line game addiction and fifteen adolescents without problematic on-line game play and an intact family structure were recruited. Over 3 weeks, families were asked to carry out homework assignments focused on increasing family cohesion for more than 1 hour/day and 4 days/week. Before therapy, adolescents with on-line game addiction demonstrated decreased activity as measured by functional magnetic resonance imaging (fMRI) within the caudate, middle temporal gyrus, and occipital lobe in response to images depicting parental affection and increased activity of the middle frontal and inferior parietal in response scenes from on-line games, relative to healthy comparison subjects. Improvement in perceived family cohesion following 3 weeks of treatment was associated with an increase in the activity of the caudate nucleus in response to affection stimuli and was inversely correlated with changes in on-line game playing time. With evidence of brain activation changes in response to on-line game playing cues and images depicting parental love, the present findings suggest that family cohesion may be an important factor in the treatment of problematic on-line game playing. PMID:22698763

Mind Over Matter: The Brain's Response to Marijuana

MedlinePlus

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

Longitudinal Brain Changes Associated with Prophylactic Cranial Irradiation in Lung Cancer.

PubMed

Simó, Marta; Vaquero, Lucía; Ripollés, Pablo; Gurtubay-Antolin, Ane; Jové, Josep; Navarro, Arturo; Cardenal, Felipe; Bruna, Jordi; Rodríguez-Fornells, Antoni

2016-04-01

The toxic effects of prophylactic cranial irradiation (PCI) and platinum-based chemotherapy on cognition in the lung cancer population have not yet been well established. In the present study we examined the longitudinal neuropsychological and brain structural changes observed in patients with lung cancer who were undergoing these treatments. Twenty-two patients with small cell lung cancer (SCLC) who underwent platinum-based chemotherapy and PCI were compared with two control groups: an age- and education-matched group of healthy controls (n = 21) and a group of patients with non-SCLC (NSCLC, n = 13) who underwent platinum-based chemotherapy. All groups were evaluated using a neuropsychological battery and multimodal structural magnetic resonance imaging: T1-weighted and diffusion tensor imaging at baseline (before PCI for SCLC and chemotherapy for NSCLC) and at 3 months after treatment. T1 voxel-based morphometry and tract-based spatial statistics were used to analyze microstructural changes in gray matter (GM) and white matter (WM). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire was also completed. Patients with SCLC exhibited cognitive deterioration in verbal fluency over time. Structural magnetic resonance imaging showed decreases in GM at 3 months in the right subcortical regions, bilateral insular cortex, and superior temporal gyrus in patients with SCLC compared with both control groups. Additionally, patients with SCLC showed decreases in GM over time in the aforementioned regions plus in the right parahippocampal gyrus and hippocampus, together with changes in the WM microstructure of the entire corpus callosum. These changes had a limited impact on responses to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire, however. Patients with NSCLC showed no cognitive or brain structural differences after chemotherapy. This longitudinal study documents moderate neuropsychological deficits together with notable brain-specific structural changes (in GM and WM) in patients with SCLC after chemotherapy and PCI, suggesting that chemotherapy and especially PCI are associated with the development of cognitive and structural brain toxic effects. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

The oscillatory entrainment of virtual pitch perception

PubMed Central

Aksentijevic, Aleksandar; Northeast, Anthony; Canty, Daniel; Elliott, Mark A.

2013-01-01

Evidence suggests that synchronized brain oscillations in the low gamma range (around 33 Hz) are involved in the perceptual integration of harmonic complex tones. This process involves the binding of harmonic components into “harmonic templates” – neural structures responsible for pitch coding in the brain. We investigated the hypothesis that oscillatory harmonic binding promotes a change in pitch perception style from spectral (frequency) to virtual (relational). Using oscillatory priming we asked 24 participants to judge as rapidly as possible, the direction of an ambiguous target with ascending spectral and descending virtual contour. They made significantly more virtual responses when primed at 29, 31, and 33 Hz and when the first target tone was harmonically related to the prime, suggesting that neural synchronization in the low gamma range could facilitate a shift toward virtual pitch processing. PMID:23630515

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

PubMed

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

2016-10-01

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

Analysis of structure-function network decoupling in the brain systems of spastic diplegic cerebral palsy.

PubMed

Lee, Dongha; Pae, Chongwon; Lee, Jong Doo; Park, Eun Sook; Cho, Sung-Rae; Um, Min-Hee; Lee, Seung-Koo; Oh, Maeng-Keun; Park, Hae-Jeong

2017-10-01

Manifestation of the functionalities from the structural brain network is becoming increasingly important to understand a brain disease. With the aim of investigating the differential structure-function couplings according to network systems, we investigated the structural and functional brain networks of patients with spastic diplegic cerebral palsy with periventricular leukomalacia compared to healthy controls. The structural and functional networks of the whole brain and motor system, constructed using deterministic and probabilistic tractography of diffusion tensor magnetic resonance images and Pearson and partial correlation analyses of resting-state functional magnetic resonance images, showed differential embedding of functional networks in the structural networks in patients. In the whole-brain network of patients, significantly reduced global network efficiency compared to healthy controls were found in the structural networks but not in the functional networks, resulting in reduced structural-functional coupling. On the contrary, the motor network of patients had a significantly lower functional network efficiency over the intact structural network and a lower structure-function coupling than the control group. This reduced coupling but reverse directionality in the whole-brain and motor networks of patients was prominent particularly between the probabilistic structural and partial correlation-based functional networks. Intact (or less deficient) functional network over impaired structural networks of the whole brain and highly impaired functional network topology over the intact structural motor network might subserve relatively preserved cognitions and impaired motor functions in cerebral palsy. This study suggests that the structure-function relationship, evaluated specifically using sparse functional connectivity, may reveal important clues to functional reorganization in cerebral palsy. Hum Brain Mapp 38:5292-5306, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Structural Image Analysis of the Brain in Neuropsychology Using Magnetic Resonance Imaging (MRI) Techniques.

PubMed

Bigler, Erin D

2015-09-01

Magnetic resonance imaging (MRI) of the brain provides exceptional image quality for visualization and neuroanatomical classification of brain structure. A variety of image analysis techniques provide both qualitative as well as quantitative methods to relate brain structure with neuropsychological outcome and are reviewed herein. Of particular importance are more automated methods that permit analysis of a broad spectrum of anatomical measures including volume, thickness and shape. The challenge for neuropsychology is which metric to use, for which disorder and the timing of when image analysis methods are applied to assess brain structure and pathology. A basic overview is provided as to the anatomical and pathoanatomical relations of different MRI sequences in assessing normal and abnormal findings. Some interpretive guidelines are offered including factors related to similarity and symmetry of typical brain development along with size-normalcy features of brain anatomy related to function. The review concludes with a detailed example of various quantitative techniques applied to analyzing brain structure for neuropsychological outcome studies in traumatic brain injury.

Hemodynamic monitoring in different cortical layers with a single fiber optical system

NASA Astrophysics Data System (ADS)

Yu, Linhui; Noor, M. Sohail; Kiss, Zelma H. T.; Murari, Kartikeya

2018-02-01

Functional monitoring of highly-localized deep brain structures is of great interest. However, due to light scattering, optical methods have limited depth penetration or can only measure from a large volume. In this research, we demonstrate continuous measurement of hemodynamics in different cortical layers in response to thalamic deep brain stimulation (DBS) using a single fiber optical system. A 200-μm-core-diameter multimode fiber is used to deliver and collect light from tissue. The fiber probe can be stereotaxically implanted into the brain region of interest at any depth to measure the di use reflectance spectra from a tissue volume of 0.02-0.03 mm3 near the fiber tip. Oxygenation is then extracted from the reflectance spectra using an algorithm based on Monte Carlo simulations. Measurements were performed on the surface (cortical layer I) and at 1.5 mm depth (cortical layer VI) of the motor cortex in anesthetized rats with thalamic DBS. Preliminary results revealed the oxygenation changes in response to DBS. Moreover, the baseline as well as the stimulus-evoked change in oxygenation were different at the two depths of cortex.

A Programmable High-Voltage Compliance Neural Stimulator for Deep Brain Stimulation in Vivo

PubMed Central

Gong, Cihun-Siyong Alex; Lai, Hsin-Yi; Huang, Sy-Han; Lo, Yu-Chun; Lee, Nicole; Chen, Pin-Yuan; Tu, Po-Hsun; Yang, Chia-Yen; Lin, James Chang-Chieh; Chen, You-Yin

2015-01-01

Deep brain stimulation (DBS) is one of the most effective therapies for movement and other disorders. The DBS neurosurgical procedure involves the implantation of a DBS device and a battery-operated neurotransmitter, which delivers electrical impulses to treatment targets through implanted electrodes. The DBS modulates the neuronal activities in the brain nucleus for improving physiological responses as long as an electric discharge above the stimulation threshold can be achieved. In an effort to improve the performance of an implanted DBS device, the device size, implementation cost, and power efficiency are among the most important DBS device design aspects. This study aims to present preliminary research results of an efficient stimulator, with emphasis on conversion efficiency. The prototype stimulator features high-voltage compliance, implemented with only a standard semiconductor process, without the use of extra masks in the foundry through our proposed circuit structure. The results of animal experiments, including evaluation of evoked responses induced by thalamic electrical stimuli with our fabricated chip, were shown to demonstrate the proof of concept of our design. PMID:26029954

Neural basis of bilingual language control.

PubMed

Calabria, Marco; Costa, Albert; Green, David W; Abutalebi, Jubin

2018-06-19

Acquiring and speaking a second language increases demand on the processes of language control for bilingual as compared to monolingual speakers. Language control for bilingual speakers involves the ability to keep the two languages separated to avoid interference and to select one language or the other in a given conversational context. This ability is what we refer with the term "bilingual language control" (BLC). It is now well established that the architecture of this complex system of language control encompasses brain networks involving cortical and subcortical structures, each responsible for different cognitive processes such as goal maintenance, conflict monitoring, interference suppression, and selective response inhibition. Furthermore, advances have been made in determining the overlap between the BLC and the nonlinguistic executive control networks, under the hypothesis that the BLC processes are just an instantiation of a more domain-general control system. Here, we review the current knowledge about the neural basis of these control systems. Results from brain imaging studies of healthy adults and on the performance of bilingual individuals with brain damage are discussed. © 2018 New York Academy of Sciences.

Activity-Dependent NPAS4 Expression and the Regulation of Gene Programs Underlying Plasticity in the Central Nervous System

PubMed Central

2013-01-01

The capability of the brain to change functionally in response to sensory experience is most active during early stages of development but it decreases later in life when major alterations of neuronal network structures no longer take place in response to experience. This view has been recently challenged by experimental strategies based on the enhancement of environmental stimulation levels, genetic manipulations, and pharmacological treatments, which all have demonstrated that the adult brain retains a degree of plasticity that allows for a rewiring of neuronal circuitries over the entire life course. A hot spot in the field of neuronal plasticity centres on gene programs that underlie plastic phenomena in adulthood. Here, I discuss the role of the recently discovered neuronal-specific and activity-dependent transcription factor NPAS4 as a critical mediator of plasticity in the nervous system. A better understanding of how modifications in the connectivity of neuronal networks occur may shed light on the treatment of pathological conditions such as brain damage or disease in adult life, some of which were once considered untreatable. PMID:24024041

Brain-derived-neurotrophic-factor (BDNF) stress response in rats bred for learned helplessness.

PubMed

Vollmayr, B; Faust, H; Lewicka, S; Henn, F A

2001-07-01

Stress-induced elevation of glucocorticoids is accompanied by structural changes and neuronal damage in certain brain areas. This includes reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus which can be prevented by chronic electroconvulsive seizures and antidepressant drug treatment. In the last years we have bred two strains of rats, one which reacts with congenital helplessness to stress (cLH), and one which congenitally does not acquire helplessness when stressed (cNLH). After being selectively bred for more than 40 generations these strains have lost their behavioural plasticity including their sensitivity to antidepressant treatment. We show here that in cLH rats, acute immobilization stress does not induce a reduction of BDNF expression in the hippocampus which is observed in Sprague--Dawley and cNLH rats. All animals tested exhibited elevated corticosterone levels when stressed, an indication, that in cLH rats regulation of BDNF expression in the hippocampal formation is uncoupled from corticosterone increase induced through stress. This may explain the lack of adaptive responses in this strain.

Structural covariance of brain region volumes is associated with both structural connectivity and transcriptomic similarity.

PubMed

Yee, Yohan; Fernandes, Darren J; French, Leon; Ellegood, Jacob; Cahill, Lindsay S; Vousden, Dulcie A; Spencer Noakes, Leigh; Scholz, Jan; van Eede, Matthijs C; Nieman, Brian J; Sled, John G; Lerch, Jason P

2018-05-18

An organizational pattern seen in the brain, termed structural covariance, is the statistical association of pairs of brain regions in their anatomical properties. These associations, measured across a population as covariances or correlations usually in cortical thickness or volume, are thought to reflect genetic and environmental underpinnings. Here, we examine the biological basis of structural volume covariance in the mouse brain. We first examined large scale associations between brain region volumes using an atlas-based approach that parcellated the entire mouse brain into 318 regions over which correlations in volume were assessed, for volumes obtained from 153 mouse brain images via high-resolution MRI. We then used a seed-based approach and determined, for 108 different seed regions across the brain and using mouse gene expression and connectivity data from the Allen Institute for Brain Science, the variation in structural covariance data that could be explained by distance to seed, transcriptomic similarity to seed, and connectivity to seed. We found that overall, correlations in structure volumes hierarchically clustered into distinct anatomical systems, similar to findings from other studies and similar to other types of networks in the brain, including structural connectivity and transcriptomic similarity networks. Across seeds, this structural covariance was significantly explained by distance (17% of the variation, up to a maximum of 49% for structural covariance to the visceral area of the cortex), transcriptomic similarity (13% of the variation, up to maximum of 28% for structural covariance to the primary visual area) and connectivity (15% of the variation, up to a maximum of 36% for structural covariance to the intermediate reticular nucleus in the medulla) of covarying structures. Together, distance, connectivity, and transcriptomic similarity explained 37% of structural covariance, up to a maximum of 63% for structural covariance to the visceral area. Additionally, this pattern of explained variation differed spatially across the brain, with transcriptomic similarity playing a larger role in the cortex than subcortex, while connectivity explains structural covariance best in parts of the cortex, midbrain, and hindbrain. These results suggest that both gene expression and connectivity underlie structural volume covariance, albeit to different extents depending on brain region, and this relationship is modulated by distance. Copyright © 2018. Published by Elsevier Inc.

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.

Transduction of Nonhuman Primate Brain with Adeno-Associated Virus Serotype 1: Vector Trafficking and Immune Response

PubMed Central

Forsayeth, John; Mirek, Hanna; Munson, Keith; Bringas, John; Pivirotto, Phil; McBride, Jodi L; Davidson, Beverly L.; Bankiewicz, Krystof S.

2009-01-01

Abstract We used convection-enhanced delivery (CED) to characterize gene delivery mediated by adeno-associated virus type 1 (AAV1) by tracking expression of hrGFP (humanized green fluorescent protein from Renilla reniformis) into the striatum, basal forebrain, and corona radiata of monkey brain. Four cynomolgus monkeys received single infusions into corona radiata, putamen, and caudate. The other group (n = 4) received infusions into basal forebrain. Thirty days after infusion animals were killed and their brains were processed for immunohisto-chemical evaluation. Volumetric analysis of GFP-positive brain areas was performed. AAV1-hrGFP infusions resulted in approximately 550, 700, and 73 mm3 coverage after infusion into corona radiata, striatum, and basal forebrain, respectively. Aside from targeted regions, other brain structures also showed GFP signal (internal and external globus pallidus, subthalamic nucleus), supporting the idea that AAV1 is actively trafficked to regions distal from the infusion site. In addition to neuronal transduction, a significant nonneuronal cell population was transduced by AAV1 vector; for example, oligodendrocytes in corona radiata and astrocytes in the striatum. We observed a strong humoral and cell-mediated response against AAV1-hrGFP in transduced monkeys irrespective of the anatomic location of the infusion, as evidenced by induction of circulating anti-AAV1 and anti-hrGFP antibodies, as well as infiltration of CD4+ lymphocytes and upregulation of MHC-II in regions infused with vector. We conclude that transduction of antigen-presenting cells within the CNS is a likely cause of this response and that caution is warranted when foreign transgenes are used as reporters in gene therapy studies with vectors with broader tropism than AAV2. PMID:19292604

Brain Emotion Systems, Personality, Hopelessness, Self/Other Perception, and Gambling Cognition: A Structural Equation Model.

PubMed

Iliceto, Paolo; D'Antuono, Laura; Bowden-Jones, Henrietta; Giovani, Eleni; Giacolini, Teodosio; Candilera, Gabriella; Sabatello, Ugo; Panksepp, Jaak

2016-03-01

The aim of this study was to explore the relations between gambling, brain emotion systems, personality, self/other perception, and hopelessness in an Italian community. Dimensions of gambling, positive and negative emotions, self/other perception, personality and hopelessness were assessed in a community sample of 235 adults aged 19-59 years. Two structural models were tested. We found a significant correlation between problem gambling and impulsivity, which in association with aggressivity and negative personality dimensions may help explain the psychopathology factor, i.e. a latent variable involving neurotic personality, hopelessness, high sensation seeking, low metacognitive responsiveness, and disorganized patterns of interpersonal relationships. These results contribute to develop a theoretical framework of gambling in relation with personality factors and provide a new approach for clinical intervention of problem gambling that relies on a solid multidimensional perspective.

Cerebellum and personality traits.

PubMed

Petrosini, Laura; Cutuli, Debora; Picerni, Eleonora; Laricchiuta, Daniela

2015-02-01

Personality traits are multidimensional traits comprising cognitive, emotional, and behavioral characteristics, and a wide array of cerebral structures mediate individual variability. Differences in personality traits covary with brain morphometry in specific brain regions. A cerebellar role in emotional and affective processing and on personality characteristics has been suggested. In a large sample of healthy subjects of both sexes and differently aged, the macro- and micro-structural variations of the cerebellum were correlated with the scores obtained in the Temperament and Character Inventory (TCI) by Cloninger. Cerebellar volumes were associated positively with Novelty Seeking scores and negatively with Harm Avoidance scores. Given the cerebellar contribution in personality traits and emotional processing, we investigated the cerebellar involvement even in alexithymia, construct of personality characterized by impairment in cognitive, emotional, and affective processing. Interestingly, the subjects with high alexithymic traits had larger volumes in the bilateral Crus 1. The cerebellar substrate for some personality dimensions extends the relationship between personality and brain areas to a structure up to now thought to be involved mainly in motor and cognitive functions, much less in emotional processes and even less in personality individual differences. The enlarged volumes of Crus 1 in novelty seekers and alexithymics support the tendency to action featuring both personality constructs. In fact, Novelty Seeking and alexithymia are rooted in behavior and inescapably have a strong action component, resulting in stronger responses in the structures more focused on action and embodiment, as the cerebellum is.

Variability comparison of simultaneous brain near-infrared spectroscopy (NIRS) and functional MRI (fMRI) during visual stimulation

PubMed Central

Minati, Ludovico; Visani, Elisa; Dowell, Nick G; Medford, Nick; Critchley, Hugo D

2011-01-01

Brain near-infrared spectroscopy (NIRS) is emerging as a potential alternative to functional MRI (fMRI). To date, no study has explicitly compared the two techniques in terms of measurement variability, a key parameter dictating attainable statistical power. Here, NIRS and fMRI were simultaneously recorded during event-related visual stimulation. Inter-subject coefficients of variation (CVs) for peak response amplitude were considerably larger for NIRS than fMRI, but inter-subject CVs for response latency and intra-subject CVs for response amplitude were overall comparable. Our results may represent an optimistic estimate of the CVs of NIRS measurements, as optode positioning was guided by structural MRI, which is normally unavailable. We conclude that fMRI may be preferable to NIRS for group comparisons, but NIRS is equally powerful when comparing conditions within participants. The discrepancy between inter- and intra-subject CVs is likely related to variability in head anatomy and tissue properties which may be better accounted for by emerging NIRS technology. PMID:21780948

Neurophysiologic intraoperative monitoring of the vestibulocochlear nerve.

PubMed

Simon, Mirela V

2011-12-01

Neurosurgical procedures involving the skull base and structures within can pose a significant risk of damage to the brain stem and cranial nerves. This can have life-threatening consequences and/or result in devastating neurologic deficits. Over the past decade, intraoperative neurophysiology has significantly evolved and currently offers a great tool for live monitoring of the integrity of nervous structures. Thus, dysfunction can be identified early and prompt modification of the surgical management or operating conditions, leads to avoidance of permanent structural damage.Along these lines, the vestibulocochlear nerve (CN VIII) and, to a greater extent, the auditory pathways as they pass through the brain stem are especially at risk during cerebelopontine angle (CPA), posterior/middle fossa, or brain stem surgery. CN VIII can be damaged by several mechanisms, from vascular compromise to mechanical injury by stretch, compression, dissection, and heat injury. Additionally, cochlea itself can be significantly damaged during temporal bone drilling, by noise, mechanical destruction, or infarction, and because of rupture, occlusion, or vasospasm of the internal auditory artery.CN VIII monitoring can be successfully achieved by live recording of the function of one of its parts, the cochlear or auditory nerve (AN), using the brain stem auditory evoked potentials (BAEPs), electrocochleography (ECochG), and compound nerve action potentials (CNAPs) of the cochlear nerve.This is a review of these techniques, their principle, applications, methodology, interpretation of the evoked responses, and their change from baseline, within the context of surgical and anesthesia environments, and finally the appropriate management of these changes.

Effects of One Year of Spaceflight on Neurocognitive Function

NASA Technical Reports Server (NTRS)

Seidler, R. D.; Mulavara, A. P.; Koppelmans, V.; Kofman, I. S.; Cassady, K.; Yuan , P.; De Dios, Y. E.; Gadd, N.; Riascos, R. F.; Wood, S. J.;

Brain activity elicited by viewing pictures of the own virtually amputated body predicts xenomelia.

PubMed

Oddo-Sommerfeld, Silvia; Hänggi, Jürgen; Coletta, Ludovico; Skoruppa, Silke; Thiel, Aylin; Stirn, Aglaja V

2018-01-08

Xenomelia is a rare condition characterized by the persistent desire for the amputation of physically healthy limbs. Prior studies highlighted the importance of superior and inferior parietal lobuli (SPL/IPL) and other sensorimotor regions as key brain structures associated with xenomelia. We expected activity differences in these areas in response to pictures showing the desired body state, i.e. that of an amputee in xenomelia. Functional magnetic resonance images were acquired in 12 xenomelia individuals and 11 controls while they viewed pictures of their own real and virtually amputated body. Pictures were rated on several dimensions. Multivariate statistics using machine learning was performed on imaging data. Brain activity when viewing pictures of one's own virtually amputated body predicted group membership accurately with a balanced accuracy of 82.58% (p = 0.002), sensitivity of 83.33% (p = 0.018), specificity of 81.82% (p = 0.015) and an area under the ROC curve of 0.77. Among the highest predictive brain regions were bilateral SPL, IPL, and caudate nucleus, other limb representing areas, but also occipital regions. Pleasantness and attractiveness ratings were higher for amputated bodies in xenomelia. Findings show that neuronal processing in response to pictures of one's own desired body state is different in xenomelia compared with controls and might represent a neuronal substrate of the xenomelia complaints that become behaviourally relevant, at least when rating the pleasantness and attractiveness of one's own body. Our findings converge with structural peculiarities reported in xenomelia and partially overlap in task and results with that of anorexia and transgender research. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of the antagonism of nicotine by mecamylamine and pempidine in the brain

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

Martin, T.J.

1989-01-01

Antagonists have been crucial in the characterization of nicotine's pharmacology. Initial evidence for the existence of central nicotinic receptors was based on the fact that nicotine produced a number of behavioral effects that were antagonized by ganglionic blockers that crossed the blood-brain barrier, such as mecamylamine and pempidine. These compounds are thought to be noncompetitive antagonists due to the fact that they do not compete for agonist binding to brain homogenate in vitro. However, pharmacological evidence in support of noncompetitive antagonism is lacking. Dose-response curves for nicotine were determined in the presence of various doses of pempidine for depression ofmore » spontaneous activity and antinociception in mice. Pempidine was found to shift the dose response curves for these effects of nicotine in a manner consistent with noncompetitive antagonism. A number of mecamylamine analogs were investigated for antagonism of these central effects of nicotine as well. These studies revealed that the N-, 2-, and 3-methyls were crucial for optimal efficacy and potency and suggests that these compounds possess a specific mechanism of action, possibly involving a receptor. Furthermore, the structure-activity relationships for the mecamylamine analogs were found to be different than that previously reported for the agonists, suggesting that they do not act at the same site. The binding of ({sup 3} H)-L-nicotine and ({sup 3}H)-pempidine was studied in vitro to mouse brain homogentate and in situ to rat brain slices. The in situ binding of ({sup 3}H)-L-nicotine to rat brain slices was quantitated autoradiographically to discrete brain areas in the presence and absence of 1, 10 and 100 {mu}M nicotine and pempidine. Pempidine did not effectively displace ({sup 3}H)-L-nicotine binding.« less

Glycemic extremes in youth with T1DM: the structural and functional integrity of the developing brain.

PubMed

Arbelaez, Ana Maria; Semenkovich, Katherine; Hershey, Tamara

2013-12-01

The adult brain accounts for a disproportionally large percentage of the body’s total energy consumption (1). However, during brain development,energy demand is even higher, reaching the adult rate by age 2 and increasing to nearly twice the adult rate by age 10, followed by gradual reduction toward adult levels in the next decade (1,2). The dramatic changes in brain metabolism occurring over the first two decades of life coincide with the initial proliferation and then pruning of synapses to adult levels.The brain derives its energy almost exclusively from glucose and is largely driven by neuronal signaling, biosynthesis, and neuroprotection (3–6).Glucose homeostasis in the body is tightly regulated by a series of hormones and physiologic responses. As a result, hypoglycemia and hyperglycemia are rare occurrences in normal individuals, but they occur commonly inpatients with type 1 diabetes mellitus (T1DM) due to a dysfunction of peripheral glucose-insulin-glucagon responses and non-physiologic doses of exogenous insulin, which imperfectly mimic normal physiology. These extremes can occur more frequently in children and adolescents with T1DM due to the inadequacies of insulin replacement therapy, events leading to the diagnosis [prolonged untreated hyperglycemia and diabetic ketoacidosis (DKA)], and to behavioral factors interfering with optimal treatment. When faced with fluctuations in glucose supply the metabolism of the body and brain change dramatically, largely to conserve resources and, at a cost to other organs, to preserve brain function (7). However,if the normal physiological mechanisms that prevent these severe glucose fluctuations and maintain homeostasis are impaired, neuronal function and potentially viability can be affected (8–11).

Brain structural plasticity in survivors of a major earthquake

PubMed Central

Lui, Su; Chen, Long; Yao, Li; Xiao, Yuan; Wu, Qi-Zhu; Zhang, Jun-Ran; Huang, Xiao-Qi; Zhang, Wei; Wang, Yu-Qin; Chen, Hua-Fu; Chan, Raymond C.K.; Sweeney, John A.; Gong, Qi-Yong

2013-01-01

Background Stress responses have been studied extensively in animal models, but effects of major life stress on the human brain remain poorly understood. The aim of this study was to determine whether survivors of a major earthquake, who were presumed to have experienced extreme emotional stress during the disaster, demonstrate differences in brain anatomy relative to individuals who have not experienced such stressors. Methods Healthy survivors living in an area devastated by a major earthquake and matched healthy controls underwent 3-dimentional high-resolution magnetic resonance imaging (MRI). Survivors were scanned 13–25 days after the earthquake; controls had undergone MRI for other studies not long before the earthquake. We used optimized voxel-based morphometry analysis to identify regional differences of grey matter volume between the survivors and controls. Results We included 44 survivors (17 female, mean age 37 [standard deviation (SD) 10.6] yr) and 38 controls (14 female, mean age 35.3 [SD 11.2] yr) in our analysis. Compared with controls, the survivors showed significantly lower grey matter volume in the bilateral insula, hippocampus, left caudate and putamen, and greater grey matter volume in the bilateral orbitofrontal cortex and the parietal lobe (all p < 0.05, corrected for multiple comparison). Limitations Differences in the variance of survivor and control data could impact study findings. Conclusion Acute anatomic alterations could be observed in earthquake survivors in brain regions where functional alterations after stress have been described. Anatomic changes in the present study were observed earlier than previously reported and were seen in prefrontal–limbic, parietal and striatal brain systems. Together with the results of previous functional imaging studies, our observations suggest a complex pattern of human brain response to major life stress affecting brain systems that modulate and respond to heightened affective arousal. PMID:23710694

Evolutionary aspects of human exercise--born to run purposefully.

PubMed

Mattson, Mark P

2012-07-01

This article is intended to raise awareness of the adaptive value of endurance exercise (particularly running) in the evolutionary history of humans, and the implications of the genetic disposition to exercise for the aging populations of modern technology-driven societies. The genome of Homo sapiens has evolved to support the svelte phenotype of an endurance runner, setting him/her apart from all other primates. The cellular and molecular mechanisms underlying the competitive advantages conferred by exercise capacity in youth can also provide a survival benefit beyond the reproductive period. These mechanisms include up-regulation of genes encoding proteins involved in protecting cells against oxidative stress, disposing of damaged proteins and organelles, and enhancing bioenergetics. Particularly fascinating are the signaling mechanisms by which endurance running changes the structure and functional capabilities of the brain and, conversely, the mechanisms by which the brain integrates metabolic, cardiovascular and behavioral responses to exercise. As an emerging example, I highlight the roles of brain-derived neurotrophic factor (BDNF) as a mediator of the effects of exercise on the brain, and BDNF's critical role in regulating metabolic and cardiovascular responses to endurance running. A better understanding of such 'healthspan-extending' actions of endurance exercise may lead to new approaches for improving quality of life as we advance in the coming decades and centuries. Published by Elsevier B.V.

Inhibition of angiogenesis by β-galactosylceramidase deficiency in globoid cell leukodystrophy

PubMed Central

Belleri, Mirella; Ronca, Roberto; Coltrini, Daniela; Nico, Beatrice; Ribatti, Domenico; Poliani, Pietro L.; Giacomini, Arianna; Alessi, Patrizia; Marchesini, Sergio; Santos, Marta B.; Bongarzone, Ernesto R.

2013-01-01

Globoid cell leukodystrophy (Krabbe disease) is a neurological disorder of infants caused by genetic deficiency of the lysosomal enzyme β-galactosylceramidase leading to accumulation of the neurotoxic metabolite 1-β-d-galactosylsphingosine (psychosine) in the central nervous system. Angiogenesis plays a pivotal role in the physiology and pathology of the brain. Here, we demonstrate that psychosine has anti-angiogenic properties by causing the disassembling of endothelial cell actin structures at micromolar concentrations as found in the brain of patients with globoid cell leukodystrophy. Accordingly, significant alterations of microvascular endothelium were observed in the post-natal brain of twitcher mice, an authentic model of globoid cell leukodystrophy. Also, twitcher endothelium showed a progressively reduced capacity to respond to pro-angiogenic factors, defect that was corrected after transduction with a lentiviral vector harbouring the murine β-galactosylceramidase complementary DNA. Finally, RNA interference-mediated β-galactosylceramidase gene silencing causes psychosine accumulation in human endothelial cells and hampers their mitogenic and motogenic response to vascular endothelial growth factor. Accordingly, significant alterations were observed in human microvasculature from brain biopsy of a globoid cell leukodystrophy case. Together these data demonstrate that β-galactosylceramidase deficiency induces significant alterations in endothelial neovascular responses that may contribute to central nervous system and systemic damages that occur in globoid cell leukodystrophy. PMID:23983033

Evolutionary Aspects of Human Exercise – Born to Run Purposefully

PubMed Central

Mattson, Mark P.

2012-01-01

This article is intended to raise awareness of the adaptive value of endurance exercise (particularly running) in the evolutionary history of humans, and the implications of the genetic disposition to exercise for the aging populations of modern technology-driven societies. The genome of Homo sapiens has evolved to support the svelte phenotype of an endurance runner, setting him/her apart from all other primates. The cellular and molecular mechanisms underlying the competitive advantages conferred by exercise capacity in youth can also provide a survival benefit beyond the reproductive period. These mechanisms include up-regulation of genes encoding proteins involved in protecting cells against oxidative stress, disposing of damaged proteins and organelles, and enhancing bioenergetics. Particularly fascinating are the signaling mechanisms by which endurance running changes the structure and functional capabilities of the brain and, conversely, the mechanisms by which the brain integrates metabolic, cardiovascular and behavioral responses to exercise. As an emerging example, I highlight the roles of brain-derived neurotrophic factor (BDNF) as a mediator of the effects of exercise on the brain, and BDNF s critical role in regulating metabolic and cardiovascular responses to endurance running. A better understanding of such healthspan-extending actions of endurance exercise may lead to new approaches for improving quality of life as we advance in the coming decades and centuries. PMID:22394472

A Skew-t space-varying regression model for the spectral analysis of resting state brain activity.

PubMed

Ismail, Salimah; Sun, Wenqi; Nathoo, Farouk S; Babul, Arif; Moiseev, Alexader; Beg, Mirza Faisal; Virji-Babul, Naznin

2013-08-01

It is known that in many neurological disorders such as Down syndrome, main brain rhythms shift their frequencies slightly, and characterizing the spatial distribution of these shifts is of interest. This article reports on the development of a Skew-t mixed model for the spatial analysis of resting state brain activity in healthy controls and individuals with Down syndrome. Time series of oscillatory brain activity are recorded using magnetoencephalography, and spectral summaries are examined at multiple sensor locations across the scalp. We focus on the mean frequency of the power spectral density, and use space-varying regression to examine associations with age, gender and Down syndrome across several scalp regions. Spatial smoothing priors are incorporated based on a multivariate Markov random field, and the markedly non-Gaussian nature of the spectral response variable is accommodated by the use of a Skew-t distribution. A range of models representing different assumptions on the association structure and response distribution are examined, and we conduct model selection using the deviance information criterion. (1) Our analysis suggests region-specific differences between healthy controls and individuals with Down syndrome, particularly in the left and right temporal regions, and produces smoothed maps indicating the scalp topography of the estimated differences.

Early Alzheimer's and Parkinson's Disease Pathology in Urban Children: Friend versus Foe Responses—It Is Time to Face the Evidence

PubMed Central

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

2013-01-01

Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HPπ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health. PMID:23509683

The Self-Liking Brain: A VBM Study on the Structural Substrate of Self-Esteem

PubMed Central

Agroskin, Dmitrij; Klackl, Johannes; Jonas, Eva

2014-01-01

Abundant evidence suggests that self-esteem is an important personality resource for emotion regulation in response to stressful experiences. It was thus hypothesized that the relative grey matter volume of brain regions involved in responding to and coping with stress is related to individual differences in trait self-esteem. Using structural magnetic resonance imaging of 48 healthy adults in conjunction with voxel-based morphometry and diffeomorphic anatomical registration using exponentiated lie algebra (VBM-DARTEL), positive associations between self-esteem and regional grey matter volume were indeed found in the anterior cingulate cortex (ACC), right lateral prefrontal cortex (LPFC), right hippocampus, and left hypothalamus. In addition, self-esteem positively covaried with grey matter volume in the right temporo-parietal junction (TPJ), which has been implicated in pride and theory of mind. The results suggest that persons with low self-esteem have reduced grey matter volume in brain regions that contribute to emotion/stress regulation, pride, and theory of mind. The findings provide novel neuroanatomical evidence for the view that self-esteem constitutes a vital coping resource. PMID:24489727

Differences in Monoamine Oxidase Activity in the Brain of Wistar and August Rats with High and Low Locomotor Activity: A Cytochemical Study.

PubMed

Sergutina, A V; Rakhmanova, V I

2016-06-01

Monoamine oxidase activity was quantitatively assessed by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampal CA3 field) of rats of August line and Wistar population with high and low locomotor activity in the open fi eld test. Monoamine oxidase activity (substrate tryptamine) predominated in the nucleus accumbens of Wistar rats with high motor activity in comparison with rats with low locomotor activity. In August rats, enzyme activity (substrates tryptamine and serotonin) predominated in the hippocampus of animals with high motor activity. Comparison of August rats with low locomotor activity and Wistar rats with high motor activity (i.e. animals demonstrating maximum differences in motor function) revealed significantly higher activity of the enzyme (substrates tryptamine and serotonin) in the hippocampus of Wistar rats. The study demonstrates clear-cut morphochemical specificity of monoaminergic metabolism based on the differences in the cytochemical parameter "monoamine oxidase activity", in the studied brain structures, responsible for the formation and realization of goal-directed behavior in Wistar and August rats.

Ventromedial Hypothalamus and the Generation of Aggression

PubMed Central

Hashikawa, Yoshiko; Hashikawa, Koichi; Falkner, Annegret L.; Lin, Dayu

2017-01-01

Aggression is a costly behavior, sometimes with severe consequences including death. Yet aggression is prevalent across animal species ranging from insects to humans, demonstrating its essential role in the survival of individuals and groups. The question of how the brain decides when to generate this costly behavior has intrigued neuroscientists for over a century and has led to the identification of relevant neural substrates. Various lesion and electric stimulation experiments have revealed that the hypothalamus, an ancient structure situated deep in the brain, is essential for expressing aggressive behaviors. More recently, studies using precise circuit manipulation tools have identified a small subnucleus in the medial hypothalamus, the ventrolateral part of the ventromedial hypothalamus (VMHvl), as a key structure for driving both aggression and aggression-seeking behaviors. Here, we provide an updated summary of the evidence that supports a role of the VMHvl in aggressive behaviors. We will consider our recent findings detailing the physiological response properties of populations of VMHvl cells during aggressive behaviors and provide new understanding regarding the role of the VMHvl embedded within the larger whole-brain circuit for social sensation and action. PMID:29375329

Structural differences in the brain between wild and laboratory rats (Rattus norvegicus): potential contribution to wariness.

PubMed

Koizumi, Ryoko; Kiyokawa, Yasushi; Mikami, Kaori; Ishii, Akiko; Tanaka, Kazuyuki D; Tanikawa, Tsutomu; Takeuchi, Yukari

2018-05-11

Wild animals typically exhibit defensive behaviors in response to a wider range and/or a weaker intensity of stimuli compared with domestic animals. However, little is known about the neural mechanisms underlying "wariness" in wild animals. Wild rats are one of the most accessible wild animals for experimental research. Laboratory rats are a domesticated form of wild rat, belonging to the same species, and are therefore considered suitable control animals for wild rats. Based on these factors, we analyzed structural differences in the brain between wild and laboratory rats to elucidate the neural mechanisms underlying wariness. We examined wild rats trapped in Tokyo, and weight-matched laboratory rats. We then prepared brain sections and compared the basolateral complex of the amygdala (BLA), the bed nucleus of the stria terminalis (BNST), the main olfactory bulb, and the accessory olfactory bulb. The results revealed that wild rats exhibited larger BLA, BNST and caudal part of the accessory olfactory bulb compared with laboratory rats. These results suggest that the BLA, BNST, and vomeronasal system potentially contribute to wariness in wild rats.

The self-liking brain: a VBM study on the structural substrate of self-esteem.

PubMed

Agroskin, Dmitrij; Klackl, Johannes; Jonas, Eva

2014-01-01

Abundant evidence suggests that self-esteem is an important personality resource for emotion regulation in response to stressful experiences. It was thus hypothesized that the relative grey matter volume of brain regions involved in responding to and coping with stress is related to individual differences in trait self-esteem. Using structural magnetic resonance imaging of 48 healthy adults in conjunction with voxel-based morphometry and diffeomorphic anatomical registration using exponentiated lie algebra (VBM-DARTEL), positive associations between self-esteem and regional grey matter volume were indeed found in the anterior cingulate cortex (ACC), right lateral prefrontal cortex (LPFC), right hippocampus, and left hypothalamus. In addition, self-esteem positively covaried with grey matter volume in the right temporo-parietal junction (TPJ), which has been implicated in pride and theory of mind. The results suggest that persons with low self-esteem have reduced grey matter volume in brain regions that contribute to emotion/stress regulation, pride, and theory of mind. The findings provide novel neuroanatomical evidence for the view that self-esteem constitutes a vital coping resource.

[Changes in Spatial Organization of Cortical Rhythm Vibrations in Children uner the Influence of Music].

PubMed

Shepovalnikov, A N; Egorov, M V

2015-01-01

Changes is systemic brain activity under influence of classical music (minor and major music) were studied at two groups of healthy children aged 5-6 years (n = 53). In 25 of studied children the Luscher test showed increased level of anxiety which significantly decreased after music therapy sessions. Bioelectrical cortical activity registered from 20 unipolar leads was subjected to correlation, coherence and factor analysis. Also the dynamics of the power spectrum for each of the EEG was studied. According to EEG all children after listening to both minor and major tones showed reorganization of brain rhythm structure accompanied by a decrease in the level of coherence and correlation of EEG; also was found significant and almost universal decrease in the EEG power spectrum. Registered EEG changes under the influence of classical music seems to reflect a decrease in excess of "internal tension" and weakening degree of "stiffness" to ensure the activity of cerebral structures responsible for mechanisms of "basic integration" which maintain constant readiness of brain to rapid and complete inclusion in action.

Neural dynamics for landmark orientation and angular path integration

PubMed Central

Seelig, Johannes D.; Jayaraman, Vivek

2015-01-01

Summary Many animals navigate using a combination of visual landmarks and path integration. In mammalian brains, head direction cells integrate these two streams of information by representing an animal's heading relative to landmarks, yet maintaining their directional tuning in darkness based on self-motion cues. Here we use two-photon calcium imaging in head-fixed flies walking on a ball in a virtual reality arena to demonstrate that landmark-based orientation and angular path integration are combined in the population responses of neurons whose dendrites tile the ellipsoid body — a toroidal structure in the center of the fly brain. The population encodes the fly's azimuth relative to its environment, tracking visual landmarks when available and relying on self-motion cues in darkness. When both visual and self-motion cues are absent, a representation of the animal's orientation is maintained in this network through persistent activity — a potential substrate for short-term memory. Several features of the population dynamics of these neurons and their circular anatomical arrangement are suggestive of ring attractors — network structures proposed to support the function of navigational brain circuits. PMID:25971509

Different brain structures associated with artistic and scientific creativity: a voxel-based morphometry study.

PubMed

Shi, Baoguo; Cao, Xiaoqing; Chen, Qunlin; Zhuang, Kaixiang; Qiu, Jiang

2017-02-21

Creativity is the ability to produce original and valuable ideas or behaviors. In real life, artistic and scientific creativity promoted the development of human civilization; however, to date, no studies have systematically investigated differences in the brain structures responsible for artistic and scientific creativity in a large sample. Using voxel-based morphometry (VBM), this study identified differences in regional gray matter volume (GMV) across the brain between artistic and scientific creativity (assessed by the Creative Achievement Questionnaire) in 356 young, healthy subjects. The results showed that artistic creativity was significantly negatively associated with the regional GMV of the supplementary motor area (SMA) and anterior cingulate cortex (ACC). In contrast, scientific creativity was significantly positively correlated with the regional GMV of the left middle frontal gyrus (MFG) and left inferior occipital gyrus (IOG). Overall, artistic creativity was associated with the salience network (SN), whereas scientific creativity was associated with the executive attention network and semantic processing. These results may provide an effective marker that can be used to predict and evaluate individuals' creative performance in the fields of science and art.

Different brain structures associated with artistic and scientific creativity: a voxel-based morphometry study

PubMed Central

Shi, Baoguo; Cao, Xiaoqing; Chen, Qunlin; Zhuang, Kaixiang; Qiu, Jiang

2017-01-01

Creativity is the ability to produce original and valuable ideas or behaviors. In real life, artistic and scientific creativity promoted the development of human civilization; however, to date, no studies have systematically investigated differences in the brain structures responsible for artistic and scientific creativity in a large sample. Using voxel-based morphometry (VBM), this study identified differences in regional gray matter volume (GMV) across the brain between artistic and scientific creativity (assessed by the Creative Achievement Questionnaire) in 356 young, healthy subjects. The results showed that artistic creativity was significantly negatively associated with the regional GMV of the supplementary motor area (SMA) and anterior cingulate cortex (ACC). In contrast, scientific creativity was significantly positively correlated with the regional GMV of the left middle frontal gyrus (MFG) and left inferior occipital gyrus (IOG). Overall, artistic creativity was associated with the salience network (SN), whereas scientific creativity was associated with the executive attention network and semantic processing. These results may provide an effective marker that can be used to predict and evaluate individuals’ creative performance in the fields of science and art. PMID:28220826

The Role of Medical Imaging in the Recharacterization of Mild Traumatic Brain Injury Using Youth Sports as a Laboratory

PubMed Central

Talavage, Thomas M.; Nauman, Eric A.; Leverenz, Larry J.

2016-01-01

The short- and long-term impact of mild traumatic brain injury (TBI) is an increasingly vital concern for both military and civilian personnel. Such injuries produce significant social and financial burdens and necessitate improved diagnostic and treatment methods. Recent integration of neuroimaging and biomechanical studies in youth collision-sport athletes has revealed that significant alterations in brain structure and function occur even in the absence of traditional clinical markers of “concussion.” While task performance is maintained, athletes exposed to repetitive head accelerations exhibit structural changes to the underlying white matter, altered glial cell metabolism, aberrant vascular response, and marked changes in functional network behavior. Moreover, these changes accumulate with accrued years of exposure, suggesting a cumulative trauma mechanism that may culminate in categorization as “concussion” and long-term neurological deficits. The goal of this review is to elucidate the role of medical imaging in recharacterizing TBI, as a whole, to better identify at-risk individuals and improve the development of preventative and interventional approaches. PMID:26834695

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

Michaelides, M.; Wang, G.; Michaelides, M.

Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated imagemore » registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.« less

SU-E-QI-12: Morphometry Based Measurements of the Structural Response to Whole Brain Radiation

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

Fuentes, D; Castillo, R; Castillo, E

2014-06-15

Purpose: Although state of the art radiation therapy techniques for treating intracranial malignancies have eliminated acute brain injury, cognitive impairment occurs in 50–90% of patients who survive >6mo post irradiation. Quantitative characterization of therapy response is needed to facilitate therapeutic strategies to minimize radiation induced cognitive impairment [1]. Deformation based morphometry techniques [2, 3] are presented as a quantitative imaging biomarker of therapy response in patients receiving whole brain radiation for treating medulloblastoma. Methods: Post-irradiation magnetic resonance imaging (MRI) data sets were retrospectively analyzed in N=15 patients, >60 MR image datasets. As seen in Fig 1(a), volume changes at multiplemore » time points post-irradiation were quantitatively measured in the cerebrum and ventricles with respect to pre-irradiation MRI. A high resolution image Template, was registered to the pre-irradiation MRI of each patient to create a brain atlas for the cerebrum, cerebellum, and ventricles. Skull stripped images for each patient were registered to the initial pre-treatment scan. Average volume changes in the labeled regions were measured using the determinant of the displacement field Jacobian. Results: Longitudinal measurements, Fig 1(b-c), show a negative correlation p=.06, of the cerebral volume change with the time interval from irradiation. A corresponding positive correlation, p=.01, between ventricular volume change and time interval from irradiation is seen. One sample t-test for correlations were computed using a Spearman method. An average decrease in cerebral volume, p=.08, and increase in ventricular volume, p<.001, was observed. The radiation dose was seen directly proportional to the induced volume changes in the cerebrum, r=−.44, p<.001, Fig 1(d). Conclusion: Results indicate that morphometric monitoring of brain tissue volume changes may potentially be used to quantitatively assess toxicity and response to radiation and may provide insight in developing new therapeutic approaches and monitoring efficacy.« less

A comparison of functional magnetic resonance imaging findings in children with and without a history of early exposure to general anesthesia.

PubMed

Taghon, Thomas A; Masunga, Abigail N; Small, Robert H; Kashou, Nasser H

2015-03-01

Functional magnetic resonance imaging (fMRI) has been used to evaluate the long-term consequences of early exposure to neurotoxic agents. fMRI shows that different patterns of brain activation occur in ethanol-exposed subjects performing a go/no-go response inhibition task. Pharmacologically, ethanol and general anesthetics have similar receptor-level activity in the brain. This study utilizes fMRI to examine brain activation patterns in children exposed to general anesthesia and surgery during early brain development. After obtaining Nationwide Children's Hospital IRB approval, a surgical database was utilized to identify children aged 10-17 years with a history of at least 1 h of exposure to general anesthetics and surgery when they were between 0 and 24 months of age. Age- and gender-matched children without anesthesia exposure were recruited as a control group. All subjects were scanned while being presented with a go/no-go response inhibition task. Reaction time and accuracy data were acquired, and the blood-oxygen-level-dependent (BOLD) fMRI signal was measured as a biomarker for regional neuronal activity. There were no differences in terms of performance accuracy and response time. The analysis did not reveal any significant activation differences in the primary region of interest (prefrontal cortex and caudate nucleus); however, activation differences were seen in other structures, including the cerebellum, cingulate gyrus, and paracentral lobule. Early anesthetic exposure and surgery did not affect accuracy, response time, or activation patterns in the primary region of interest during performance of the task. Intergroup differences in activation patterns in other areas of the brain were observed, and the significance of these findings is unknown. fMRI appears to be a useful tool in evaluating the long-term effects of early exposure to general anesthesia. © 2015 John Wiley & Sons Ltd.

Use of Monoclonal Antibodies to Study the Structure and Function of Nicotinic Acetylcholine Receptors on Electric Organ and Muscle and to Determine the Structure of Nicotinic Acetylcholine Receptors on Neurons

DTIC Science & Technology

1988-03-16

receptors in muscle is responsible for the muscular weakness characteristic of myasthenia gravis . Some insecticides can act like chemical warfare...expresses muscle-like acetyi-.holine receptor by observing that autoantibodies from myasthenia gravis patients reacted as well with these receptors as...Antibodies in sera from patients with myasthenia gravis do not bind to acetylcholine receptors from human brain. J Neuroimmunol 16:205-213. 21. Whiting

The Stress Model of Chronic Pain: Evidence from Basal Cortisol and Hippocampal Structure and Function in Humans

ERIC Educational Resources Information Center

Vachon-Presseau, Etienne; Roy, Mathieu; Martel, Marc-Olivier; Caron, Etienne; Marin, Marie-France; Chen, Jeni; Albouy, Genevieve; Plante, Isabelle; Sullivan, Michael J.; Lupien, Sonia J.; Rainville, Pierre

2013-01-01

Recent theories have suggested that chronic pain could be partly maintained by maladaptive physiological responses of the organism facing a recurrent stressor. The present study examined the associations between basal levels of cortisol collected over seven consecutive days, the hippocampal volumes and brain activation to thermal stimulations…

fMRI BOLD response to the eyes task in offspring from multiplex alcohol dependence families.

PubMed

Hill, Shirley Y; Kostelnik, Bryan; Holmes, Brian; Goradia, Dhruman; McDermott, Michael; Diwadkar, Vaibhav; Keshavan, Matcheri

2007-12-01

Increased susceptibility for developing alcohol dependence (AD) may be related to structural and functional differences in brain circuits that influence social cognition and more specifically, theory of mind (ToM). Alcohol dependent individuals have a greater likelihood of having deficits in social skills and greater social alienation. These characteristics may be related to inherited differences in the neuroanatomical network that comprises the social brain. Adolescent/young adult participants from multiplex AD families and controls (n = 16) were matched for gender, age, IQ, education, and handedness and administered the Eyes Task of Baron-Cohen during functional magnetic resonance imaging (fMRI). High-risk (HR) subjects showed significantly diminished blood oxygen level dependent (BOLD) response in comparison with low-risk control young adults in the right middle temporal gyrus (RMTG) and the left inferior frontal gyrus (LIFG), areas that have previously been implicated in ToM tasks. Offspring from multiplex families for AD may manifest one aspect of their genetic susceptibility by having a diminished BOLD response in brain regions associated with performance of ToM tasks. These results suggest that those at risk for developing AD may have reduced ability to empathize with others' state of mind, possibly resulting in diminished social skill.

Sex differences in impulsivity and brain morphometry in methamphetamine users

PubMed Central

Kogachi, Shannon; Chang, Linda; Alicata, Daniel; Cunningham, Eric; Ernst, Thomas

2016-01-01

Methamphetamine (METH) is an addictive stimulant, and METH users have abnormal brain structures and function. The aims of this study were to investigate the relationships between impulsivity, brain structures, and possible sex-specific differences between METH users and non-drug using Controls. Structural MRI and the Barratt Impulsiveness Scale (BIS) questionnaire were completed in 124 subjects: 62 METH (ages 41.2 ± 1.4 years, 34 males) and 62 Controls (ages 43.3 ± 2.3 years, 36 males). Independent and interactive effects of METH use status and sex were evaluated. Relationships between METH usage characteristics, brain morphometry, and impulsivity scores were examined. METH users had higher impulsivity scores, on both the Cognitive and Behavioral Factors from the BIS (p < 0.0001–0.0001). Compared with same-sex Controls, male METH users had larger, while female METH users had smaller, right superior frontal cortex (interaction-p = 0.0005). The male METH users with larger frontal volumes and female METH users with smaller or thinner frontal cortices had greater Cognitive impulsivity (interaction-p ≤ 0.05). Only female METH users showed relatively larger nucleus accumbens (interaction-p = 0.03). Greater impulsivity and thinner frontal cortices in METH users are validated. Larger superior frontal cortex in male METH users with greater cognitive impulsivity suggest decreased dendritic pruning during adolescence might have contributed to their impulsive and drug use behaviors. In the female METH users, smaller frontal cortices and the associated greater impulsivity suggest greater neurotoxicity to these brain regions, while their relatively larger nucleus accumbens suggest an estrogen-mediated neuroprotective glial response. Men and women may be affected differently by METH use. PMID:27095357

Sex differences in impulsivity and brain morphometry in methamphetamine users.

PubMed

Kogachi, Shannon; Chang, Linda; Alicata, Daniel; Cunningham, Eric; Ernst, Thomas

2017-01-01

Methamphetamine (METH) is an addictive stimulant, and METH users have abnormal brain structures and function. The aims of this study were to investigate the relationships between impulsivity, brain structures, and possible sex-specific differences between METH users and non-drug using Controls. Structural MRI and the Barratt Impulsiveness Scale (BIS) questionnaire were completed in 124 subjects: 62 METH (ages 41.2 ± 1.4 years, 34 males) and 62 Controls (ages 43.3 ± 2.3 years, 36 males). Independent and interactive effects of METH use status and sex were evaluated. Relationships between METH usage characteristics, brain morphometry, and impulsivity scores were examined. METH users had higher impulsivity scores, on both the Cognitive and Behavioral Factors from the BIS (p < 0.0001-0.0001). Compared with same-sex Controls, male METH users had larger, while female METH users had smaller, right superior frontal cortex (interaction-p = 0.0005). The male METH users with larger frontal volumes and female METH users with smaller or thinner frontal cortices had greater Cognitive impulsivity (interaction-p ≤ 0.05). Only female METH users showed relatively larger nucleus accumbens (interaction-p = 0.03). Greater impulsivity and thinner frontal cortices in METH users are validated. Larger superior frontal cortex in male METH users with greater cognitive impulsivity suggest decreased dendritic pruning during adolescence might have contributed to their impulsive and drug use behaviors. In the female METH users, smaller frontal cortices and the associated greater impulsivity suggest greater neurotoxicity to these brain regions, while their relatively larger nucleus accumbens suggest an estrogen-mediated neuroprotective glial response. Men and women may be affected differently by METH use.

Structural connectivity of right frontal hyperactive areas scales with stuttering severity.

PubMed

Neef, Nicole E; Anwander, Alfred; Bütfering, Christoph; Schmidt-Samoa, Carsten; Friederici, Angela D; Paulus, Walter; Sommer, Martin

2018-01-01

A neuronal sign of persistent developmental stuttering is the magnified coactivation of right frontal brain regions during speech production. Whether and how stuttering severity relates to the connection strength of these hyperactive right frontal areas to other brain areas is an open question. Scrutinizing such brain-behaviour and structure-function relationships aims at disentangling suspected underlying neuronal mechanisms of stuttering. Here, we acquired diffusion-weighted and functional images from 31 adults who stutter and 34 matched control participants. Using a newly developed structural connectivity measure, we calculated voxel-wise correlations between connection strength and stuttering severity within tract volumes that originated from functionally hyperactive right frontal regions. Correlation analyses revealed that with increasing speech motor deficits the connection strength increased in the right frontal aslant tract, the right anterior thalamic radiation, and in U-shaped projections underneath the right precentral sulcus. In contrast, with decreasing speech motor deficits connection strength increased in the right uncinate fasciculus. Additional group comparisons of whole-brain white matter skeletons replicated the previously reported reduction of fractional anisotropy in the left and right superior longitudinal fasciculus as well as at the junction of right frontal aslant tract and right superior longitudinal fasciculus in adults who stutter compared to control participants. Overall, our investigation suggests that right fronto-temporal networks play a compensatory role as a fluency enhancing mechanism. In contrast, the increased connection strength within subcortical-cortical pathways may be implied in an overly active global response suppression mechanism in stuttering. Altogether, this combined functional MRI-diffusion tensor imaging study disentangles different networks involved in the neuronal underpinnings of the speech motor deficit in persistent developmental stuttering. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk.

PubMed

Corlier, Fabian; Hafzalla, George; Faskowitz, Joshua; Kuller, Lewis H; Becker, James T; Lopez, Oscar L; Thompson, Paul M; Braskie, Meredith N

2018-05-15

Inflammatory processes may contribute to risk for Alzheimer's disease (AD) and age-related brain degeneration. Metabolic and genetic risk factors, and physical activity may, in turn, influence these inflammatory processes. Some of these risk factors are modifiable, and interact with each other. Understanding how these processes together relate to brain aging will help to inform future interventions to treat or prevent cognitive decline. We used brain magnetic resonance imaging (MRI) to scan 335 older adult humans (mean age 77.3 ± 3.4 years) who remained non-demented for the duration of the 9-year longitudinal study. We used structural equation modeling (SEM) in a subset of 226 adults to evaluate whether measures of baseline peripheral inflammation (serum C-reactive protein levels; CRP), mediated the baseline contributions of genetic and metabolic risk, and physical activity, to regional cortical thickness in AD-relevant brain regions at study year 9. We found that both baseline metabolic risk and AD risk variant apolipoprotein E ε4 (APOE4), modulated baseline serum CRP. Higher baseline CRP levels, in turn, predicted thinner regional cortex at year 9, and mediated an effect between higher metabolic risk and thinner cortex in those regions. A higher polygenic risk score composed of variants in immune-associated AD risk genes (other than APOE) was associated with thinner regional cortex. However, CRP levels did not mediate this effect, suggesting that other mechanisms may be responsible for the elevated AD risk. We found interactions between genetic and environmental factors and structural brain health. Our findings support the role of metabolic risk and peripheral inflammation in age-related brain decline. Copyright © 2018 Elsevier Inc. All rights reserved.

Negative childhood experiences alter a prefrontal-insular-motor cortical network in healthy adults: A preliminary multimodal rsfMRI-fMRI-MRS-dMRI study

PubMed Central

Duncan, Niall W.; Hayes, Dave J.; Wiebking, Christine; Tiret, Brice; Pietruska, Karin; Chen, David Q.; Rainville, Pierre; Marjańska, Malgorzata; Mohammid, Omar; Doyon, Julien; Hodaie, Mojgan; Northoff, Georg

2016-01-01

Research in humans and animals has shown that negative childhood experiences (NCE) can have long-term effects on the structure and function of the brain. Alterations have been noted in grey and white matter, in the brain’s resting state, on the glutamatergic system, and on neural and behavioural responses to aversive stimuli. These effects can be linked to psychiatric disorder such as depression and anxiety disorders that are influenced by excessive exposure to early life stressors. The aim of the current study was to investigate the effect of NCEs on these systems. Resting state functional MRI (rsfMRI), aversion task fMRI, glutamate magnetic resonance spectroscopy (MRS), and diffusion magnetic resonance imaging (dMRI) were combined with the Childhood Trauma Questionnaire (CTQ) in healthy subjects to examine the impact of NCEs on the brain. Low CTQ scores, a measure of NCEs, were related to higher resting state glutamate levels and higher resting state entropy in the medial prefrontal cortex (mPFC). CTQ scores, mPFC glutamate and entropy, correlated with neural BOLD responses to the anticipation of aversive stimuli in regions throughout the aversion-related network, with strong correlations between all measures in the motor cortex and left insula. Structural connectivity strength, measured using mean fractional anisotropy, between the mPFC and left insula correlated to aversion-related signal changes in the motor cortex. These findings highlight the impact of NCEs on multiple inter-related brain systems. In particular, they highlight the role of a prefrontal-insular-motor cortical network in the processing and responsivity to aversive stimuli and its potential adaptability by NCEs. PMID:26287448

Sex matters: females in proestrus show greater diazepam anxiolysis and brain-derived neurotrophin factor- and parvalbumin-positive neurons than males.

PubMed

Ravenelle, Rebecca; Berman, Ariel K; La, Jeffrey; Mason, Briana; Asumadu, Evans; Yelleswarapu, Chandra; Donaldson, S Tiffany

2018-04-01

In humans and animal models, sex differences are reported for anxiety-like behavior and response to anxiogenic stimuli. In the current work, we studied anxiety-like behavior and response to the prototypical anti-anxiety drug, diazepam. We used 6th generation outbred lines of adult Long Evans rats with high and low anxiety-like behavior phenotypes to investigate the impact of proestrus on the baseline and diazepam-induced behavior. At three doses of diazepam (0, 0.1, and 1.0 mg/kg, i.p.), we measured anxiogenic responses on the elevated plus maze of adult male and female rats. We assessed parvalbumin and brain-derived neurotrophin protein levels in forebrain and limbic structures implicated in anxiety/stress using immunohistochemistry. At baseline, we saw significant differences between anxiety lines, with high anxiety lines displaying less time on the open arms of the elevated plus maze, and less open arm entries, regardless of sex. During proestrus, high anxiety females showed less anxiety-like behavior at 0.1 mg/kg, while low anxiety females displayed less anxiety-like behavior at 0.1 and 1.0 doses, relative to males. Brain-derived neurotrophin protein was elevated in females in the medial prefrontal cortex and central amygdala, while parvalbumin-immunoreactive cells were greater in males in the medial prefrontal cortex. Parvalbumin-positive cells in high anxiety females were higher in CA2 and dentate gyrus relative to males from the same line. In sum, when tested in proestrus, females showed greater anxiolytic effects of diazepam relative to males, and this correlated with increases in neurotrophin and parvalbumin neuron density in corticolimbic structures. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Bidirectional synaptic structural plasticity after chronic cocaine administration occurs through Rap1 small GTPase signaling

PubMed Central

Cahill, Michael E.; Bagot, Rosemary C.; Gancarz, Amy M.; Walker, Deena M.; Sun, HaoSheng; Wang, Zi-Jun; Heller, Elizabeth A.; Feng, Jian; Kennedy, Pamela J.; Koo, Ja Wook; Cates, Hannah M.; Neve, Rachael L.; Shen, Li; Dietz, David M.

2016-01-01

Summary Dendritic spines are the sites of most excitatory synapses in the CNS, and opposing alterations in the synaptic structure of medium spiny neurons (MSNs) of the nucleus accumbens, a primary brain reward region, are seen at early vs. late time points after cocaine administration. Here we investigate the time-dependent molecular and biochemical processes that regulate this bidirectional synaptic structural plasticity of NAc MSNs and associated changes in cocaine reward in response to chronic cocaine exposure. Our findings reveal key roles for the bidirectional synaptic expression of the Rap1b small GTPase and an associated local-synaptic protein translation network in this process. The transcriptional mechanisms and pathway-specific inputs to NAc that regulate Rap1b expression are also characterized. Collectively, these findings provide a precise mechanism by which nuclear to synaptic interactions induce “metaplasticity” in NAc MSNs, and we reveal the specific effects of this plasticity on reward behavior in a brain circuit-specific manner. PMID:26844834

[Ultrastructural changes in the MP3 neuron of the mollusk Lymnaea stagnalis after cryopreservation of the isolated brain].

PubMed

Dmitrieva, E V; Moshkov, D A; Gakhova, E N

2006-01-01

Investigation of a possibility of long-term storage of frozen (-196 degrees C) viable neurons and nervous tissue is one of the central present day problems. In this study ultrastructural changes in neurons of frozen-thawed snail brain were examined as a function of time. We studied the influence of cryopreservation, cryoprotectant (Me2SO), cooling to 4-6 degrees C, and a prolonged incubation in physiological solution at 4-6 degrees C on dictyosomes of Golgi apparatus, endoplasmic reticulum (ER) cisternae and mitochondria. It has been found that responses of these intracellular structures of cryopreserved neurons to the above influences are similar: dissociation of Golgi dictyosomes, swelling of endoplasmic reticulum cisternae and mitochondrial cristae. Both freezing-thawing and cryoprotectant were seen to cause an increase in the number of lysosomes, liposomes, myelin-like structures, and to form large vacuoles. The structural changes in molluscan neurons caused by cryopreservation with Me2SO (2 M) were reversible.

Reduced amygdalar and hippocampal size in adults with generalized social phobia.

PubMed

Irle, Eva; Ruhleder, Mirjana; Lange, Claudia; Seidler-Brandler, Ulrich; Salzer, Simone; Dechent, Peter; Weniger, Godehard; Leibing, Eric; Leichsenring, Falk

2010-03-01

Structural and functional brain imaging studies suggest abnormalities of the amygdala and hippocampus in posttraumatic stress disorder and major depressive disorder. However, structural brain imaging studies in social phobia are lacking. In total, 24 patients with generalized social phobia (GSP) and 24 healthy controls underwent 3-dimensional structural magnetic resonance imaging of the amygdala and hippocampus and a clinical investigation. Compared with controls, GSP patients had significantly reduced amygdalar (13%) and hippocampal (8%) size. The reduction in the size of the amygdala was statistically significant for men but not women. Smaller right-sided hippocampal volumes of GSP patients were significantly related to stronger disorder severity. Our sample included only patients with the generalized subtype of social phobia. Because we excluded patients with comorbid depression, our sample may not be representative. We report for the first time volumetric results in patients with GSP. Future assessment of these patients will clarify whether these changes are reversed after successful treatment and whether they predict treatment response.

Restrained eaters show altered brain response to food odor.

PubMed

Kemmotsu, Nobuko; Murphy, Claire

2006-02-28

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

Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction.

PubMed

Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami

2018-05-01

Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.

Brain-mapping projects using the common marmoset.

PubMed

Okano, Hideyuki; Mitra, Partha

2015-04-01

Globally, there is an increasing interest in brain-mapping projects, including the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative project in the USA, the Human Brain Project (HBP) in Europe, and the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) project in Japan. These projects aim to map the structure and function of neuronal circuits to ultimately understand the vast complexity of the human brain. Brain/MINDS is focused on structural and functional mapping of the common marmoset (Callithrix jacchus) brain. This non-human primate has numerous advantages for brain mapping, including a well-developed frontal cortex and a compact brain size, as well as the availability of transgenic technologies. In the present review article, we discuss strategies for structural and functional mapping of the marmoset brain and the relation of the common marmoset to other animals models. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Annotation and Structural Analysis of Sialylated Human Milk Oligosaccharides

PubMed Central

Wu, Shuai; Grimm, Rudolf; German, J. Bruce; Lebrilla, Carlito B.

2011-01-01

Sialylated human milk oligosaccharides (SHMOs) are important components of human milk oligosaccharides. Sialic acids are typically found on the nonreducing end and are known binding sites for pathogens and aid in neonates’ brain development. Due to their negative charge and hydrophilic nature, they also help modulate cell-cell interactions. It has also been shown that sialic acids are involved in regulating the immune response and aid in brain development. In this study, the enriched SHMOs from pooled milk sample were analyzed by HPLC-Chip/QTOF MS. The instrument employs a microchip-based nano-LC column packed with porous graphitized carbon (PGC) to provide excellent isomer separation for SHMOs with highly reproducible retention time. The precursor ions were further examined with collision-induced dissociation (CID). By applying the proper collision energy, isomers can be readily differentiated by diagnostic peaks and characteristic fragmentation patterns. A set of 30 SHMO structures with retention times, accurate masses and MS/MS spectra was deduced and incorporated into an HMO library. When combined with previously determined neutral components, a library with over 70 structures is obtained allowing high-throughput oligosaccharide structure identification. PMID:21133381

Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction.

PubMed

Konova, Anna B; Moeller, Scott J; Tomasi, Dardo; Parvaz, Muhammad A; Alia-Klein, Nelly; Volkow, Nora D; Goldstein, Rita Z

2012-10-01

Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie the maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) that was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both the function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. © 2012 Published 2012. This article is a US Government work and is in the public domain in the USA.

East-West differences in perception of brain death. Review of history, current understandings, and directions for future research.

PubMed

Yang, Qing; Miller, Geoffrey

2015-06-01

The concept of brain death as equivalent to cardiopulmonary death was initially conceived following developments in neuroscience, critical care, and transplant technology. It is now a routine part of medicine in Western countries, including the United States. In contrast, Eastern countries have been reluctant to incorporate brain death into legislation and medical practice. Several countries, most notably China, still lack laws recognizing brain death and national medical standards for making the diagnosis. The perception is that Asians are less likely to approve of brain death or organ transplant from brain dead donors. Cultural and religious traditions have been referenced to explain this apparent difference. In the West, the status of the brain as home to the soul in Enlightenment philosophy, combined with pragmatism and utilitarianism, supports the concept of brain death. In the East, the integration of body with spirit and nature in Buddhist and folk beliefs, along with the Confucian social structure that builds upon interpersonal relationships, argues against brain death. However, it is unclear whether these reasoning strategies are explicitly used when families and medical providers are faced with acknowledging brain death. Their decisions are more likely to involve a prioritization of values and a rationalization of intuitive responses. Why and whether there might be differences between East and West in the acceptance of the brain death concept requires further empirical testing, which would help inform policy-making and facilitate communication between providers and patients from different cultural and ethnic backgrounds.

Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology.

PubMed

Fu, Tian-Ming; Hong, Guosong; Viveros, Robert D; Zhou, Tao; Lieber, Charles M

2017-11-21

Implantable electrical probes have led to advances in neuroscience, brain-machine interfaces, and treatment of neurological diseases, yet they remain limited in several key aspects. Ideally, an electrical probe should be capable of recording from large numbers of neurons across multiple local circuits and, importantly, allow stable tracking of the evolution of these neurons over the entire course of study. Silicon probes based on microfabrication can yield large-scale, high-density recording but face challenges of chronic gliosis and instability due to mechanical and structural mismatch with the brain. Ultraflexible mesh electronics, on the other hand, have demonstrated negligible chronic immune response and stable long-term brain monitoring at single-neuron level, although, to date, it has been limited to 16 channels. Here, we present a scalable scheme for highly multiplexed mesh electronics probes to bridge the gap between scalability and flexibility, where 32 to 128 channels per probe were implemented while the crucial brain-like structure and mechanics were maintained. Combining this mesh design with multisite injection, we demonstrate stable 128-channel local field potential and single-unit recordings from multiple brain regions in awake restrained mice over 4 mo. In addition, the newly integrated mesh is used to validate stable chronic recordings in freely behaving mice. This scalable scheme for mesh electronics together with demonstrated long-term stability represent important progress toward the realization of ideal implantable electrical probes allowing for mapping and tracking single-neuron level circuit changes associated with learning, aging, and neurodegenerative diseases. Copyright © 2017 the Author(s). Published by PNAS.

Computational neural networks in chemistry: Model free mapping devices for predicting chemical reactivity from molecular structure

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

Elrod, D.W.

1992-01-01

Computational neural networks (CNNs) are a computational paradigm inspired by the brain's massively parallel network of highly interconnected neurons. The power of computational neural networks derives not so much from their ability to model the brain as from their ability to learn by example and to map highly complex, nonlinear functions, without the need to explicitly specify the functional relationship. Two central questions about CNNs were investigated in the context of predicting chemical reactions: (1) the mapping properties of neural networks and (2) the representation of chemical information for use in CNNs. Chemical reactivity is here considered an example ofmore » a complex, nonlinear function of molecular structure. CNN's were trained using modifications of the back propagation learning rule to map a three dimensional response surface similar to those typically observed in quantitative structure-activity and structure-property relationships. The computational neural network's mapping of the response surface was found to be robust to the effects of training sample size, noisy data and intercorrelated input variables. The investigation of chemical structure representation led to the development of a molecular structure-based connection-table representation suitable for neural network training. An extension of this work led to a BE-matrix structure representation that was found to be general for several classes of reactions. The CNN prediction of chemical reactivity and regiochemistry was investigated for electrophilic aromatic substitution reactions, Markovnikov addition to alkenes, Saytzeff elimination from haloalkanes, Diels-Alder cycloaddition, and retro Diels-Alder ring opening reactions using these connectivity-matrix derived representations. The reaction predictions made by the CNNs were more accurate than those of an expert system and were comparable to predictions made by chemists.« less

Inter-subject phase synchronization for exploratory analysis of task-fMRI.

PubMed

Bolt, Taylor; Nomi, Jason S; Vij, Shruti G; Chang, Catie; Uddin, Lucina Q

2018-08-01

Analysis of task-based fMRI data is conventionally carried out using a hypothesis-driven approach, where blood-oxygen-level dependent (BOLD) time courses are correlated with a hypothesized temporal structure. In some experimental designs, this temporal structure can be difficult to define. In other cases, experimenters may wish to take a more exploratory, data-driven approach to detecting task-driven BOLD activity. In this study, we demonstrate the efficiency and power of an inter-subject synchronization approach for exploratory analysis of task-based fMRI data. Combining the tools of instantaneous phase synchronization and independent component analysis, we characterize whole-brain task-driven responses in terms of group-wise similarity in temporal signal dynamics of brain networks. We applied this framework to fMRI data collected during performance of a simple motor task and a social cognitive task. Analyses using an inter-subject phase synchronization approach revealed a large number of brain networks that dynamically synchronized to various features of the task, often not predicted by the hypothesized temporal structure of the task. We suggest that this methodological framework, along with readily available tools in the fMRI community, provides a powerful exploratory, data-driven approach for analysis of task-driven BOLD activity. Copyright © 2018 Elsevier Inc. All rights reserved.

The importance of structural anisotropy in computational models of traumatic brain injury.

PubMed

Carlsen, Rika W; Daphalapurkar, Nitin P

2015-01-01

Understanding the mechanisms of injury might prove useful in assisting the development of methods for the management and mitigation of traumatic brain injury (TBI). Computational head models can provide valuable insight into the multi-length-scale complexity associated with the primary nature of diffuse axonal injury. It involves understanding how the trauma to the head (at the centimeter length scale) translates to the white-matter tissue (at the millimeter length scale), and even further down to the axonal-length scale, where physical injury to axons (e.g., axon separation) may occur. However, to accurately represent the development of TBI, the biofidelity of these computational models is of utmost importance. There has been a focused effort to improve the biofidelity of computational models by including more sophisticated material definitions and implementing physiologically relevant measures of injury. This paper summarizes recent computational studies that have incorporated structural anisotropy in both the material definition of the white matter and the injury criterion as a means to improve the predictive capabilities of computational models for TBI. We discuss the role of structural anisotropy on both the mechanical response of the brain tissue and on the development of injury. We also outline future directions in the computational modeling of TBI.

Altered hypothalamic response to food in smokers123

PubMed Central

Geha, Paul Y; Aschenbrenner, Katja; Felsted, Jennifer; O'Malley, Stephanie S; Small, Dana M

2013-01-01

Background: Smoking cessation is often followed by weight gain. Eating behaviors and weight change have been linked to the brain response to food, but it is unknown whether smoking influences this response. Objective: We determined the influence of smoking status (smokers compared with nonsmokers) on the brain response to food in regions associated with weight changes in nonsmokers. Design: In study 1, we used functional MRI (fMRI) to identify regions of the brain associated with weight change in nonsmokers. BMI and the brain response to a milk shake, which is a palatable and energy-dense food, were measured in a group of 27 nonsmokers (5 men). Sixteen subjects (3 men) returned 1 y later for BMI reassessment. The change in BMI was regressed against the brain response to isolate regions associated with weight change. In study 2, to determine whether smokers showed altered responses in regions associated with weight change, we assessed the brain response to a milk shake in 11 smokers. The brain response to a milk shake compared with a tasteless control solution was assessed in 11 smokers (5 men) in comparison with a group of age-, sex- and body weight–matched nonsmokers selected from the pool of nonsmokers who participated in study 1. Results: The response in the midbrain, hypothalamus, thalamus, and ventral striatum was positively associated with weight change at the 1-y follow-up in 16 nonsmokers. Compared with nonsmokers, smokers had a greater response to milk shakes in the hypothalamus. Conclusion: Smokers display an altered brain response to food in the hypothalamus, which is an area associated with long-term weight change in nonsmokers. PMID:23235196

Influence of acute sleep loss on the neural correlates of alerting, orientating and executive attention components.

PubMed

Muto, Vincenzo; Shaffii-le Bourdiec, Anahita; Matarazzo, Luca; Foret, Ariane; Mascetti, Laura; Jaspar, Mathieu; Vandewalle, Gilles; Phillips, Christophe; Degueldre, Christian; Balteau, Evelyne; Luxen, André; Collette, Fabienne; Maquet, Pierre

2012-12-01

The Attention Network Test (ANT) is deemed to assess the alerting, orientating and executive components of human attention. Capitalizing on the opportunity to investigate three facets of attention in a single task, we used functional magnetic resonance imaging (fMRI) to assess the effect of sleep deprivation (SD) on brain responses associated with the three attentional components elicited by the ANT. Twelve healthy volunteers were scanned in two conditions 1 week apart, after a normal night of sleep (rested wakefulness, RW) or after one night of total sleep deprivation. Sleep deprivation was associated with a global increase in reaction times, which did not affect specifically any of the three attention effects. Brain responses associated with the alerting effect did not differ between RW and SD. Higher-order attention components (orientating and conflict effects) were associated with significantly larger thalamic responses during SD than during RW. These results suggest that SD influences different components of human attention non-selectively, through mechanisms that might either affect centrencephalic structures maintaining vigilance or ubiquitously perturb neuronal function. Compensatory responses can counter these effects transiently by recruiting thalamic responses, thereby supporting thalamocortical function. © 2012 European Sleep Research Society.

Cognitive Reserve and Brain Maintenance: Orthogonal Concepts in Theory and Practice.

PubMed

Habeck, C; Razlighi, Q; Gazes, Y; Barulli, D; Steffener, J; Stern, Y

2017-08-01

Cognitive Reserve and Brain Maintenance have traditionally been understood as complementary concepts: Brain Maintenance captures the processes underlying the structural preservation of the brain with age, and might be assessed relative to age-matched peers. Cognitive Reserve, on the other hand, refers to how cognitive processing can be performed regardless of how well brain structure has been maintained. Thus, Brain Maintenance concerns the "hardware," whereas Cognitive Reserve concerns "software," that is, brain functioning explained by factors beyond mere brain structure. We used structural brain data from 368 community-dwelling adults, age 20-80, to derive measures of Brain Maintenance and Cognitive Reserve. We found that Brain Maintenance and Cognitive were uncorrelated such that values on one measure did not imply anything about the other measure. Further, both measures were positively correlated with verbal intelligence and education, hinting at formative influences of the latter to both measures. We performed extensive split-half simulations to check our derived measures' statistical robustness. Our approach enables the out-of-sample quantification of Brain Maintenance and Cognitive Reserve for single subjects on the basis of chronological age, neuropsychological performance and structural brain measures. Future work will investigate the prognostic power of these measures with regard to future cognitive status. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Structure Shapes Dynamics and Directionality in Diverse Brain Networks: Mathematical Principles and Empirical Confirmation in Three Species

NASA Astrophysics Data System (ADS)

Moon, Joon-Young; Kim, Junhyeok; Ko, Tae-Wook; Kim, Minkyung; Iturria-Medina, Yasser; Choi, Jee-Hyun; Lee, Joseph; Mashour, George A.; Lee, Uncheol

2017-04-01

Identifying how spatially distributed information becomes integrated in the brain is essential to understanding higher cognitive functions. Previous computational and empirical studies suggest a significant influence of brain network structure on brain network function. However, there have been few analytical approaches to explain the role of network structure in shaping regional activities and directionality patterns. In this study, analytical methods are applied to a coupled oscillator model implemented in inhomogeneous networks. We first derive a mathematical principle that explains the emergence of directionality from the underlying brain network structure. We then apply the analytical methods to the anatomical brain networks of human, macaque, and mouse, successfully predicting simulation and empirical electroencephalographic data. The results demonstrate that the global directionality patterns in resting state brain networks can be predicted solely by their unique network structures. This study forms a foundation for a more comprehensive understanding of how neural information is directed and integrated in complex brain networks.

A phenome-wide examination of neural and cognitive function.

PubMed

Poldrack, R A; Congdon, E; Triplett, W; Gorgolewski, K J; Karlsgodt, K H; Mumford, J A; Sabb, F W; Freimer, N B; London, E D; Cannon, T D; Bilder, R M

2016-12-06

This data descriptor outlines a shared neuroimaging dataset from the UCLA Consortium for Neuropsychiatric Phenomics, which focused on understanding the dimensional structure of memory and cognitive control (response inhibition) functions in both healthy individuals (130 subjects) and individuals with neuropsychiatric disorders including schizophrenia (50 subjects), bipolar disorder (49 subjects), and attention deficit/hyperactivity disorder (43 subjects). The dataset includes an extensive set of task-based fMRI assessments, resting fMRI, structural MRI, and high angular resolution diffusion MRI. The dataset is shared through the OpenfMRI project, and is formatted according to the Brain Imaging Data Structure (BIDS) standard.

Neuroimmune Basis of Alcoholic Brain Damage

PubMed Central

Crews, Fulton T.; Vetreno, Ryan P.

2017-01-01

Alcohol-induced brain damage likely contributes to the dysfunctional poor decisions associated with alcohol dependence. Human alcoholics have a global loss of brain volume that is most severe in the frontal cortex. Neuroimmune gene induction by binge drinking increases neurodegeneration through increased oxidative stress, particularly NADPH oxidase-induced oxidative stress. In addition, HMGB1-TLR4 and innate immune NF-κB target genes are increased leading to persistent and sensitized neuroimmune responses to ethanol and other agents that release HMGB1 or directly stimulate TLR receptors and/or NMDA receptors. Neuroimmune signaling and glutamate excitotoxicity are linked to alcoholic neurodegeneration. Models of adolescent alcohol abuse lead to significant frontal cortical degeneration and show the most severe loss of hippocampal neurogenesis. Adolescence is a period of high risk for ethanol-induced neurodegeneration and alterations in brain structure, gene expression, and maturation of adult phenotypes. Together, these findings support the hypothesis that adolescence is a period of risk for persistent and long-lasting increases in brain neuroimmune gene expression that promote persistent and long-term increases in alcohol consumption, neuroimmune gene induction, and neurodegeneration that we find associated with alcohol use disorders. PMID:25175868

Apollo’s gift: new aspects of neurologic music therapy

PubMed Central

Altenmüller, Eckart; Schlaug, Gottfried

2015-01-01

Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music’s ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. PMID:25725918

Brain network of semantic integration in sentence reading: insights from independent component analysis and graph theoretical analysis.

PubMed

Ye, Zheng; Doñamayor, Nuria; Münte, Thomas F

2014-02-01

A set of cortical and sub-cortical brain structures has been linked with sentence-level semantic processes. However, it remains unclear how these brain regions are organized to support the semantic integration of a word into sentential context. To look into this issue, we conducted a functional magnetic resonance imaging (fMRI) study that required participants to silently read sentences with semantically congruent or incongruent endings and analyzed the network properties of the brain with two approaches, independent component analysis (ICA) and graph theoretical analysis (GTA). The GTA suggested that the whole-brain network is topologically stable across conditions. The ICA revealed a network comprising the supplementary motor area (SMA), left inferior frontal gyrus, left middle temporal gyrus, left caudate nucleus, and left angular gyrus, which was modulated by the incongruity of sentence ending. Furthermore, the GTA specified that the connections between the left SMA and left caudate nucleus as well as that between the left caudate nucleus and right thalamus were stronger in response to incongruent vs. congruent endings. Copyright © 2012 Wiley Periodicals, Inc.

Apollo's gift: new aspects of neurologic music therapy.

PubMed

Altenmüller, Eckart; Schlaug, Gottfried

2015-01-01

Music listening and music making activities are powerful tools to engage multisensory and motor networks, induce changes within these networks, and foster links between distant, but functionally related brain regions with continued and life-long musical practice. These multimodal effects of music together with music's ability to tap into the emotion and reward system in the brain can be used to facilitate and enhance therapeutic approaches geared toward rehabilitating and restoring neurological dysfunctions and impairments of an acquired or congenital brain disorder. In this article, we review plastic changes in functional networks and structural components of the brain in response to short- and long-term music listening and music making activities. The specific influence of music on the developing brain is emphasized and possible transfer effects on emotional and cognitive processes are discussed. Furthermore, we present data on the potential of using musical tools and activities to support and facilitate neurorehabilitation. We will focus on interventions such as melodic intonation therapy and music-supported motor rehabilitation to showcase the effects of neurologic music therapies and discuss their underlying neural mechanisms. © 2015 Elsevier B.V. All rights reserved.

Decreased serotonin level during pregnancy alters morphological and functional characteristics of tonic nociceptive system in juvenile offspring of the rat.

PubMed

Butkevich, Irina P; Khozhai, Ludmila I; Mikhailenko, Victor A; Otellin, Vladimir A

2003-11-13

Serotonin (5-HT) contributes to the prenatal development of the central nervous system, acting as a morphogen in the young embryo and later as a neurotransmitter. This biologically active agent influences both morphological and biochemical differentiation of raphe neurons, which give rise to the descending serotonergic paths that regulate the processing of acutely evoked nociceptive inputs. The involvement of 5-HT in the prenatal development of tonic nociceptive system has not been studied. In the present study we evaluated the effects of a single injection (400 mg/kg, 2 ml, i.p.) of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA), given to pregnant rats during the critical period fetal serotonin development. The functional integrity of the tonic nociceptive response was investigated in 25 day old rats using the classic formalin test. Morphological analysis of brain structures involved in formalin-induced pain and 5-HT levels in the heads of 12-day embryos were also evaluated. Embryonic levels of 5-HT were significantly lowered by the treatment. The juvenile rats from pCPA-treated females showed altered brain morphology and cell differentiation in the developing cortex, hippocampus, raphe nuclei, and substantia nigra. In the formalin test, there were significant decreases in the intensity and duration of the second phase of the formalin-induced response, characterizing persistent, tonic pain. The extent of impairments in the brain structures correlated positively with the level of decrease in the behavioral responses. The data demonstrate the involvement of 5-HT in the prenatal development of the tonic nociceptive system. The decreased tonic component of the behavioral response can be explained by lower activity of the descending excitatory serotonergic system originating in the raphe nuclei, resulting in decreased tonic pain processing organized at the level of the dorsal horn of the spinal cord.

TSPO Expression and Brain Structure in the Psychosis Spectrum.

PubMed

Hafizi, Sina; Guma, Elisa; Koppel, Alex; Da Silva, Tania; Kiang, Michael; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo M; Chakravarty, M Mallar; Mizrahi, Romina

2018-06-12

Psychosis is associated with abnormal structural changes in the brain including decreased regional brain volumes and abnormal brain morphology. However, the underlying causes of these structural abnormalities are less understood. The immune system, including microglial activation, has been implicated in the pathophysiology of psychosis. Although previous studies have suggested a connection between peripheral proinflammatory cytokines and structural brain abnormalities in schizophrenia, no in-vivo studies have investigated whether microglial activation is also linked to brain structure alterations previously observed in schizophrenia and its putative prodrome. In this study, we investigated the link between mitochondrial 18kDa translocator protein (TSPO) and structural brain characteristics (i.e. regional brain volume, cortical thickness, and hippocampal shape) in key brain regions such as dorsolateral prefrontal cortex and hippocampus of a large group of participants (N = 90) including individuals at clinical high risk (CHR) for psychosis, first-episode psychosis (mostly antipsychotic naïve) patients, and healthy volunteers. The participants underwent structural brain MRI scan and [ 18 F]FEPPA positron emission tomography (PET) targeting TSPO. A significant [ 18 F]FEPPA binding-by-group interaction was observed in morphological measures across the left hippocampus. In first-episode psychosis, we observed associations between [ 18 F]FEPPA V T (total volume of distribution) and outward and inward morphological alterations, respectively, in the dorsal and ventro-medial portions of the left hippocampus. These associations were not significant in CHR or healthy volunteers. There was no association between [ 18 F]FEPPA V T and other structural brain characteristics. Our findings suggest a link between TSPO expression and alterations in hippocampal morphology in first-episode psychosis. Copyright © 2018. Published by Elsevier Inc.

Abnormal salience signaling in schizophrenia: The role of integrative beta oscillations.

PubMed

Liddle, Elizabeth B; Price, Darren; Palaniyappan, Lena; Brookes, Matthew J; Robson, Siân E; Hall, Emma L; Morris, Peter G; Liddle, Peter F

2016-04-01

Aberrant salience attribution and cerebral dysconnectivity both have strong evidential support as core dysfunctions in schizophrenia. Aberrant salience arising from an excess of dopamine activity has been implicated in delusions and hallucinations, exaggerating the significance of everyday occurrences and thus leading to perceptual distortions and delusional causal inferences. Meanwhile, abnormalities in key nodes of a salience brain network have been implicated in other characteristic symptoms, including the disorganization and impoverishment of mental activity. A substantial body of literature reports disruption to brain network connectivity in schizophrenia. Electrical oscillations likely play a key role in the coordination of brain activity at spatially remote sites, and evidence implicates beta band oscillations in long-range integrative processes. We used magnetoencephalography and a task designed to disambiguate responses to relevant from irrelevant stimuli to investigate beta oscillations in nodes of a network implicated in salience detection and previously shown to be structurally and functionally abnormal in schizophrenia. Healthy participants, as expected, produced an enhanced beta synchronization to behaviorally relevant, as compared to irrelevant, stimuli, while patients with schizophrenia showed the reverse pattern: a greater beta synchronization in response to irrelevant than to relevant stimuli. These findings not only support both the aberrant salience and disconnectivity hypotheses, but indicate a common mechanism that allows us to integrate them into a single framework for understanding schizophrenia in terms of disrupted recruitment of contextually appropriate brain networks. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Abnormal salience signaling in schizophrenia: The role of integrative beta oscillations

PubMed Central

Liddle, Elizabeth B.; Price, Darren; Palaniyappan, Lena; Brookes, Matthew J.; Robson, Siân E.; Hall, Emma L.; Morris, Peter G.

2016-01-01

Abstract Aberrant salience attribution and cerebral dysconnectivity both have strong evidential support as core dysfunctions in schizophrenia. Aberrant salience arising from an excess of dopamine activity has been implicated in delusions and hallucinations, exaggerating the significance of everyday occurrences and thus leading to perceptual distortions and delusional causal inferences. Meanwhile, abnormalities in key nodes of a salience brain network have been implicated in other characteristic symptoms, including the disorganization and impoverishment of mental activity. A substantial body of literature reports disruption to brain network connectivity in schizophrenia. Electrical oscillations likely play a key role in the coordination of brain activity at spatially remote sites, and evidence implicates beta band oscillations in long‐range integrative processes. We used magnetoencephalography and a task designed to disambiguate responses to relevant from irrelevant stimuli to investigate beta oscillations in nodes of a network implicated in salience detection and previously shown to be structurally and functionally abnormal in schizophrenia. Healthy participants, as expected, produced an enhanced beta synchronization to behaviorally relevant, as compared to irrelevant, stimuli, while patients with schizophrenia showed the reverse pattern: a greater beta synchronization in response to irrelevant than to relevant stimuli. These findings not only support both the aberrant salience and disconnectivity hypotheses, but indicate a common mechanism that allows us to integrate them into a single framework for understanding schizophrenia in terms of disrupted recruitment of contextually appropriate brain networks. Hum Brain Mapp 37:1361‐1374, 2016. © 2016 Wiley Periodicals, Inc. PMID:26853904

Transcripts with in silico predicted RNA structure are enriched everywhere in the mouse brain

PubMed Central

2012-01-01

Background Post-transcriptional control of gene expression is mostly conducted by specific elements in untranslated regions (UTRs) of mRNAs, in collaboration with specific binding proteins and RNAs. In several well characterized cases, these RNA elements are known to form stable secondary structures. RNA secondary structures also may have major functional implications for long noncoding RNAs (lncRNAs). Recent transcriptional data has indicated the importance of lncRNAs in brain development and function. However, no methodical efforts to investigate this have been undertaken. Here, we aim to systematically analyze the potential for RNA structure in brain-expressed transcripts. Results By comprehensive spatial expression analysis of the adult mouse in situ hybridization data of the Allen Mouse Brain Atlas, we show that transcripts (coding as well as non-coding) associated with in silico predicted structured probes are highly and significantly enriched in almost all analyzed brain regions. Functional implications of these RNA structures and their role in the brain are discussed in detail along with specific examples. We observe that mRNAs with a structure prediction in their UTRs are enriched for binding, transport and localization gene ontology categories. In addition, after manual examination we observe agreement between RNA binding protein interaction sites near the 3’ UTR structures and correlated expression patterns. Conclusions Our results show a potential use for RNA structures in expressed coding as well as noncoding transcripts in the adult mouse brain, and describe the role of structured RNAs in the context of intracellular signaling pathways and regulatory networks. Based on this data we hypothesize that RNA structure is widely involved in transcriptional and translational regulatory mechanisms in the brain and ultimately plays a role in brain function. PMID:22651826

Imaging Predictors of Improvement From a Motor Learning-Based Intervention for Children With Unilateral Cerebral Palsy.

PubMed

Schertz, Mitchell; Shiran, Shelly I; Myers, Vicki; Weinstein, Maya; Fattal-Valevski, Aviva; Artzi, Moran; Ben Bashat, Dafna; Gordon, Andrew M; Green, Dido

2016-08-01

Background Motor-learning interventions may improve hand function in children with unilateral cerebral palsy (UCP) but with inconsistent outcomes across participants. Objective To examine if pre-intervention brain imaging predicts benefit from bimanual intervention. Method Twenty children with UCP with Manual Ability Classification System levels I to III, aged 7-16 years, participated in an intensive bimanual intervention. Assessments included the Assisting Hand Assessment (AHA), Jebsen Taylor Test of Hand Function (JTTHF) and Children's Hand Experience Questionnaire (CHEQ) at baseline (T1), completion (T2) and 8-10 weeks post-intervention (T3). Imaging at baseline included conventional structural (radiological score), functional (fMRI) and diffusion tensor imaging (DTI). Results Improvements were seen across assessments; AHA (P = 0.04), JTTHF (P < .001) and CHEQ (P < 0.001). Radiological score significantly correlated with improvement at T2; AHA (r = .475) and CHEQ (r = .632), but negatively with improvement on unimanual measures at T3 (JTTFH r = -.514). fMRI showed negative correlations between contralesional brain activation when moving the affected hand and AHA improvements (T2: r = -.562, T3: r = -0.479). Fractional Anisotropy in the affected posterior limb of the internal capsule correlated negatively with increased bimanual use on CHEQ at T2 (r = -547) and AHA at T3 (r = -.656). Conclusions Children with greater structural, functional and connective brain damage showed enhanced responses to bimanual intervention. Baseline imaging may identify parameters predicting response to intervention in children with UCP. © The Author(s) 2015.

Brain machine interfaces combining microelectrode arrays with nanostructured optical biochemical sensors

NASA Astrophysics Data System (ADS)

Hajj-Hassan, Mohamad; Gonzalez, Timothy; Ghafer-Zadeh, Ebrahim; Chodavarapu, Vamsy; Musallam, Sam; Andrews, Mark

2009-02-01

Neural microelectrodes are an important component of neural prosthetic systems which assist paralyzed patients by allowing them to operate computers or robots using their neural activity. These microelectrodes are also used in clinical settings to localize the locus of seizure initiation in epilepsy or to stimulate sub-cortical structures in patients with Parkinson's disease. In neural prosthetic systems, implanted microelectrodes record the electrical potential generated by specific thoughts and relay the signals to algorithms trained to interpret these thoughts. In this paper, we describe novel elongated multi-site neural electrodes that can record electrical signals and specific neural biomarkers and that can reach depths greater than 8mm in the sulcus of non-human primates (monkeys). We hypothesize that additional signals recorded by the multimodal probes will increase the information yield when compared to standard probes that record just electropotentials. We describe integration of optical biochemical sensors with neural microelectrodes. The sensors are made using sol-gel derived xerogel thin films that encapsulate specific biomarker responsive luminophores in their nanostructured pores. The desired neural biomarkers are O2, pH, K+, and Na+ ions. As a prototype, we demonstrate direct-write patterning to create oxygen-responsive xerogel waveguide structures on the neural microelectrodes. The recording of neural biomarkers along with electrical activity could help the development of intelligent and more userfriendly neural prosthesis/brain machine interfaces as well as aid in providing answers to complex brain diseases and disorders.

Direct Recordings of Pitch Responses from Human Auditory Cortex

PubMed Central

Griffiths, Timothy D.; Kumar, Sukhbinder; Sedley, William; Nourski, Kirill V.; Kawasaki, Hiroto; Oya, Hiroyuki; Patterson, Roy D.; Brugge, John F.; Howard, Matthew A.

2010-01-01

Summary Pitch is a fundamental percept with a complex relationship to the associated sound structure [1]. Pitch perception requires brain representation of both the structure of the stimulus and the pitch that is perceived. We describe direct recordings of local field potentials from human auditory cortex made while subjects perceived the transition between noise and a noise with a regular repetitive structure in the time domain at the millisecond level called regular-interval noise (RIN) [2]. RIN is perceived to have a pitch when the rate is above the lower limit of pitch [3], at approximately 30 Hz. Sustained time-locked responses are observed to be related to the temporal regularity of the stimulus, commonly emphasized as a relevant stimulus feature in models of pitch perception (e.g., [1]). Sustained oscillatory responses are also demonstrated in the high gamma range (80–120 Hz). The regularity responses occur irrespective of whether the response is associated with pitch perception. In contrast, the oscillatory responses only occur for pitch. Both responses occur in primary auditory cortex and adjacent nonprimary areas. The research suggests that two types of pitch-related activity occur in humans in early auditory cortex: time-locked neural correlates of stimulus regularity and an oscillatory response related to the pitch percept. PMID:20605456

Brain Structure and Executive Functions in Children with Cerebral Palsy: A Systematic Review

ERIC Educational Resources Information Center

Weierink, Lonneke; Vermeulen, R. Jeroen; Boyd, Roslyn N.

2013-01-01

This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using…

Hemispheric specialization in affective responses, cerebral dominance for language, and handedness: Lateralization of emotion, language, and dexterity.

PubMed

Costanzo, Elsa Yolanda; Villarreal, Mirta; Drucaroff, Lucas Javier; Ortiz-Villafañe, Manuel; Castro, Mariana Nair; Goldschmidt, Micaela; Wainsztein, Agustina Edith; Ladrón-de-Guevara, María Soledad; Romero, Carlos; Brusco, Luis Ignacio; Camprodon, Joan A; Nemeroff, Charles; Guinjoan, Salvador Martín

2015-07-15

Hemispheric specialization in affective responses has received little attention in the literature. This is a fundamental variable to understand circuit dynamics of networks subserving emotion. In this study we put to test a modified "valence" hypothesis of emotion processing, considering that sadness and happiness are processed by each hemisphere in relation to dominance for language and handedness. Mood induction and language activation during functional magnetic resonance imaging (fMRI) were used in 20 right-handed and 20 nonright-handed subjects, focusing on interconnected regions known to play critical roles in affective responses: subgenual cingulate cortex, amygdala, and anterior insular cortex. We observed a consistent relationship between lateralization of affective processing, motor dexterity, and language in individuals with clear right-handedness. Sadness induces a greater activation of right-hemisphere cortical structures in right-handed, left-dominant individuals, which is not evident in nonright-handed subjects who show no consistent hemispheric dominance for language. In anterior insula, right-handed individuals displayed reciprocal activation of either hemisphere depending upon mood valence, whereas amygdala activation was predominantly left-sided regardless of mood valence. Nonright-handed individuals exhibited less consistent brain lateralization of affective processing regardless of language and motor dexterity lateralization. In contrast with traditional views on emotion processing lateralization, hemispheric specialization in affective responses is not a unitary process but is specific to the brain structure being activated. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of skull flexural properties on brain response during dynamic head loading - biomed 2013.

PubMed

Harrigan, T P; Roberts, J C; Ward, E E; Carneal, C M; Merkle, A C

2013-01-01

The skull-brain complex is typically modeled as an integrated structure, similar to a fluid-filled shell. Under dynamic loads, the interaction of the skull and the underlying brain, cerebrospinal fluid, and other tissue produces the pressure and strain histories that are the basis for many theories meant to describe the genesis of traumatic brain injury. In addition, local bone strains are of interest for predicting skull fracture in blunt trauma. However, the role of skull flexure in the intracranial pressure response to blunt trauma is complex. Since the relative time scales for pressure and flexural wave transmission across the skull are not easily separated, it is difficult to separate out the relative roles of the mechanical components in this system. This study uses a finite element model of the head, which is validated for pressure transmission to the brain, to assess the influence of skull table flexural stiffness on pressure in the brain and on strain within the skull. In a Human Head Finite Element Model, the skull component was modified by attaching shell elements to the inner and outer surfaces of the existing solid elements that modeled the skull. The shell elements were given the properties of bone, and the existing solid elements were decreased so that the overall stiffness along the surface of the skull was unchanged, but the skull table bending stiffness increased by a factor of 2.4. Blunt impact loads were applied to the frontal bone centrally, using LS-Dyna. The intracranial pressure predictions and the strain predictions in the skull were compared for models with and without surface shell elements, showing that the pressures in the mid-anterior and mid-posterior of the brain were very similar, but the strains in the skull under the loads and adjacent to the loads were decreased 15% with stiffer flexural properties. Pressure equilibration to nearly hydrostatic distributions occurred, indicating that the important frequency components for typical impact loading are lower than frequencies based on pressure wave propagation across the skull. This indicates that skull flexure has a local effect on intracranial pressures but that the integrated effect of a dome-like structure under load is a significant part of load transfer in the skull in blunt trauma.

Highly scalable multichannel mesh electronics for stable chronic brain electrophysiology

PubMed Central

Fu, Tian-Ming; Hong, Guosong; Viveros, Robert D.; Zhou, Tao

2017-01-01

Implantable electrical probes have led to advances in neuroscience, brain−machine interfaces, and treatment of neurological diseases, yet they remain limited in several key aspects. Ideally, an electrical probe should be capable of recording from large numbers of neurons across multiple local circuits and, importantly, allow stable tracking of the evolution of these neurons over the entire course of study. Silicon probes based on microfabrication can yield large-scale, high-density recording but face challenges of chronic gliosis and instability due to mechanical and structural mismatch with the brain. Ultraflexible mesh electronics, on the other hand, have demonstrated negligible chronic immune response and stable long-term brain monitoring at single-neuron level, although, to date, it has been limited to 16 channels. Here, we present a scalable scheme for highly multiplexed mesh electronics probes to bridge the gap between scalability and flexibility, where 32 to 128 channels per probe were implemented while the crucial brain-like structure and mechanics were maintained. Combining this mesh design with multisite injection, we demonstrate stable 128-channel local field potential and single-unit recordings from multiple brain regions in awake restrained mice over 4 mo. In addition, the newly integrated mesh is used to validate stable chronic recordings in freely behaving mice. This scalable scheme for mesh electronics together with demonstrated long-term stability represent important progress toward the realization of ideal implantable electrical probes allowing for mapping and tracking single-neuron level circuit changes associated with learning, aging, and neurodegenerative diseases. PMID:29109247

Neuronal glycogen synthesis contributes to physiological aging

PubMed Central

Sinadinos, Christopher; Valles-Ortega, Jordi; Boulan, Laura; Solsona, Estel; Tevy, Maria F; Marquez, Mercedes; Duran, Jordi; Lopez-Iglesias, Carmen; Calbó, Joaquim; Blasco, Ester; Pumarola, Marti; Milán, Marco; Guinovart, Joan J

2014-01-01

Glycogen is a branched polymer of glucose and the carbohydrate energy store for animal cells. In the brain, it is essentially found in glial cells, although it is also present in minute amounts in neurons. In humans, loss-of-function mutations in laforin and malin, proteins involved in suppressing glycogen synthesis, induce the presence of high numbers of insoluble polyglucosan bodies in neuronal cells. Known as Lafora bodies (LBs), these deposits result in the aggressive neurodegeneration seen in Lafora’s disease. Polysaccharide-based aggregates, called corpora amylacea (CA), are also present in the neurons of aged human brains. Despite the similarity of CA to LBs, the mechanisms and functional consequences of CA formation are yet unknown. Here, we show that wild-type laboratory mice also accumulate glycogen-based aggregates in the brain as they age. These structures are immunopositive for an array of metabolic and stress-response proteins, some of which were previously shown to aggregate in correlation with age in the human brain and are also present in LBs. Remarkably, these structures and their associated protein aggregates are not present in the aged mouse brain upon genetic ablation of glycogen synthase. Similar genetic intervention in Drosophila prevents the accumulation of glycogen clusters in the neuronal processes of aged flies. Most interestingly, targeted reduction of Drosophila glycogen synthase in neurons improves neurological function with age and extends lifespan. These results demonstrate that neuronal glycogen accumulation contributes to physiological aging and may therefore constitute a key factor regulating age-related neurological decline in humans. PMID:25059425

Breaking ignorance: the case of the brain.

PubMed

Wekerle, H

2006-01-01

Immunological self-tolerance is maintained through diverse mechanisms, including deletion of autoreactive immune cells following confrontation with autoantigen in the thymus or in the periphery and active suppression by regulatory cells. A third way to prevent autoimmunity is by hiding self tissues behind a tissue barrier impermeable for circulating immune cells. The latter mechanism has been held responsible for self-tolerance within the nervous tissue. Indeed, the nervous tissues enjoy a conditionally privileged immune status: they are normally unreachable for self-reactive T and B cells, they lack lymphatic drainage, and they are deficient in local antigen-presenting cells. Yet the immune system is by no means fully ignorant of the nervous structures. An ever-growing number of brain specific autoantigens is expressed within the thymus, which ensures an early confrontation with the unfolding T cell repertoire, and there is evidence that B cells also contact CNS-like structures outside of the brain. Then pathological processes such as neurodegeneration commonly lift the brain's immune privilege, shifting the local milieus from immune-hostile to immune-friendly. Finally, brain-reactive T cells, which abound in the healthy immune repertoire, but remain innocuous throughout life, can be activated and gain access to their target tissues. On their way, they take an ordered migration through peripheral lymphoid tissues and blood circulation, and undergo a profound reprogramming of their gene expression profile, which renders them fit to enter the nervous system and to interact with local cellule elements.

Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment.

PubMed

Ahmed, Mohamed; Cannon, Dara M; Scanlon, Cathy; Holleran, Laurena; Schmidt, Heike; McFarland, John; Langan, Camilla; McCarthy, Peter; Barker, Gareth J; Hallahan, Brian; McDonald, Colm

2015-09-01

Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity.

Episodic memory in aspects of large-scale brain networks

PubMed Central

Jeong, Woorim; Chung, Chun Kee; Kim, June Sic

2015-01-01

Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL) structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network (DMN). Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network (RSN). Altered patterns of functional connectivity (FC) among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment. PMID:26321939

Neuroprotective effect of ginger in the brain of streptozotocin-induced diabetic rats.

PubMed

El-Akabawy, Gehan; El-Kholy, Wael

2014-05-01

Diabetes mellitus results in neuronal damage caused by increased intracellular glucose leading to oxidative stress. Recent evidence revealed the potential of ginger for reducing diabetes-induced oxidative stress markers. The aim of this study is to investigate, for the first time, whether the antioxidant properties of ginger has beneficial effects on the structural brain damage associated with diabetes. We investigated the observable neurodegenerative changes in the frontal cortex, dentate gyrus, and cerebellum after 4, 6, and 8 weeks of streptozotocin (STZ)-induced diabetes in rats and the effect(s) of ginger (500 mg/kg/day). Sections of frontal cortex, dentate gyrus, and cerebellum were stained with hematoxylin and eosin and examined using light microscopy. In addition, quantitative immunohistochemical assessments of the expression of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, caspase-3, glial fibrillary acidic protein (GFAP), acetylcholinesterase (AChE), and Ki67 were performed. Our results revealed a protective role of ginger on the diabetic brain via reducing oxidative stress, apoptosis, and inflammation. In addition, this study revealed that the beneficial effect of ginger was also mediated by modulating the astroglial response to the injury, reducing AChE expression, and improving neurogenesis. These results represent a new insight into the beneficial effects of ginger on the structural alterations of diabetic brain and suggest that ginger might be a potential therapeutic strategy for the treatment of diabetic-induced damage in brain. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

PubMed Central

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

2016-01-01

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

Calcium imaging of neural circuits with extended depth-of-field light-sheet microscopy

PubMed Central

Quirin, Sean; Vladimirov, Nikita; Yang, Chao-Tsung; Peterka, Darcy S.; Yuste, Rafael; Ahrens, Misha B.

2016-01-01

Increasing the volumetric imaging speed of light-sheet microscopy will improve its ability to detect fast changes in neural activity. Here, a system is introduced for brain-wide imaging of neural activity in the larval zebrafish by coupling structured illumination with cubic phase extended depth-of-field (EDoF) pupil encoding. This microscope enables faster light-sheet imaging and facilitates arbitrary plane scanning—removing constraints on acquisition speed, alignment tolerances, and physical motion near the sample. The usefulness of this method is demonstrated by performing multi-plane calcium imaging in the fish brain with a 416 × 832 × 160 µm field of view at 33 Hz. The optomotor response behavior of the zebrafish is monitored at high speeds, and time-locked correlations of neuronal activity are resolved across its brain. PMID:26974063

Reversible Disruption of Neuronal Mitochondria by Ischemic and Traumatic Injury Revealed by Quantitative Two-Photon Imaging in the Neocortex of Anesthetized Mice

PubMed Central

Kislin, Mikhail; Sword, Jeremy; Fomitcheva, Ioulia V.; Croom, Deborah; Pryazhnikov, Evgeny; Lihavainen, Eero; Toptunov, Dmytro; Rauvala, Heikki; Ribeiro, Andre S.

2017-01-01

Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under pathological conditions, such as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries, ranging from severe to mild. Severe global ischemic injury was induced by bilateral common carotid artery occlusion, whereas severe focal stroke injury was induced by Rose Bengal photosensitization. The moderate and mild traumatic injury was inflicted by focal laser lesion and by mild photo-damage, respectively. Dendritic and mitochondrial structural changes were tracked longitudinally using transgenic mice expressing fluorescent proteins localized either in cytosol or in mitochondrial matrix. In response to severe injury, mitochondrial fragmentation developed in parallel with dendritic damage signified by dendritic beading. Reconstruction from serial section electron microscopy confirmed mitochondrial fragmentation. Unlike dendritic beading, fragmentation spread beyond the injury core in focal stroke and focal laser lesion models. In moderate and mild injury, mitochondrial fragmentation was reversible with full recovery of structural integrity after 1–2 weeks. The transient fragmentation observed in the mild photo-damage model was associated with changes in dendritic spine density without any signs of dendritic damage. Our findings indicate that alterations in neuronal mitochondria structure are very sensitive to the tissue damage and can be reversible in ischemic and traumatic injuries. SIGNIFICANCE STATEMENT During ischemic stroke or brain trauma, mitochondria can either protect neurons by supplying ATP and adsorbing excessive Ca2+, or kill neurons by releasing proapoptotic factors. Mitochondrial function is tightly linked to their morphology: healthy mitochondria are thin and long; dysfunctional mitochondria are thick (swollen) and short (fragmented). To date, fragmentation of mitochondria was studied either in dissociated cultured neurons or in brain slices, but not in the intact living brain. Using real-time in vivo two-photon microscopy, we quantified mitochondrial fragmentation during acute pathological conditions that mimic severe, moderate, and mild brain injury. We demonstrated that alterations in neuronal mitochondria structural integrity can be reversible in traumatic and ischemic injuries, highlighting mitochondria as a potential target for therapeutic interventions. PMID:28077713

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

PubMed

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

2014-01-01

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

Amino Acids That Centrally Influence Blood Pressure and Regional Blood Flow in Conscious Rats

PubMed Central

Takemoto, Yumi

2012-01-01

Functional roles of amino acids have increasingly become the focus of research. This paper summarizes amino acids that influence cardiovascular system via the brain of conscious rats. This paper firstly describes why amino acids are selected and outlines how the brain regulates blood pressure and regional blood flow. This section includes a concise history of amino acid neurotransmitters in cardiovascular research and summarizes brain areas where chemical stimulations produce blood pressure changes mainly in anesthetized animals. This is followed by comments about findings regarding several newly examined amino acids with intracisternal stimulation in conscious rats that produce changes in blood pressure. The same pressor or depressor response to central amino acid stimulations can be produced by distinct mechanisms at central and peripheral levels, which will be briefly explained. Thereafter, cardiovascular actions of some of amino acids at the mechanism level will be discussed based upon findings of pharmacological and regional blood flow measurements. Several examined amino acids in addition to the established neurotransmitter amino acids appear to differentially activate brain structures to produce changes in blood pressure and regional blood flows. They may have physiological roles in the healthy brain, but pathological roles in the brain with cerebral vascular diseases such as stroke where the blood-brain barrier is broken. PMID:22690328

Functional brain networks for learning predictive statistics.

PubMed

Giorgio, Joseph; Karlaftis, Vasilis M; Wang, Rui; Shen, Yuan; Tino, Peter; Welchman, Andrew; Kourtzi, Zoe

2017-08-18

Making predictions about future events relies on interpreting streams of information that may initially appear incomprehensible. This skill relies on extracting regular patterns in space and time by mere exposure to the environment (i.e., without explicit feedback). Yet, we know little about the functional brain networks that mediate this type of statistical learning. Here, we test whether changes in the processing and connectivity of functional brain networks due to training relate to our ability to learn temporal regularities. By combining behavioral training and functional brain connectivity analysis, we demonstrate that individuals adapt to the environment's statistics as they change over time from simple repetition to probabilistic combinations. Further, we show that individual learning of temporal structures relates to decision strategy. Our fMRI results demonstrate that learning-dependent changes in fMRI activation within and functional connectivity between brain networks relate to individual variability in strategy. In particular, extracting the exact sequence statistics (i.e., matching) relates to changes in brain networks known to be involved in memory and stimulus-response associations, while selecting the most probable outcomes in a given context (i.e., maximizing) relates to changes in frontal and striatal networks. Thus, our findings provide evidence that dissociable brain networks mediate individual ability in learning behaviorally-relevant statistics. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Interleukin-6 -174 and -572 genotypes and the volume of deep gray matter in preterm infants.

PubMed

Reiman, Milla; Parkkola, Riitta; Lapinleimu, Helena; Lehtonen, Liisa; Haataja, Leena

2009-01-01

Preterm infants have smaller cerebral and cerebellar volumes at term compared with term born infants. Perinatal factors leading to the reduction in volumes are not well known. IL-6 -174 and -572 genotypes partly regulate individual immunologic responses and have also been connected with deviant neurologic development in preterm infants. Our hypothesis was that IL-6 -174 and -572 genetic polymorphisms are associated with brain lesions and regional brain volumes in very low birth weight or in very preterm infants. DNA was genotyped for IL-6 -174 and -572 polymorphisms (GG/GC/CC). Study infants (n = 175) were categorized into three groups according to the most pathologic brain finding in ultrasound examinations until term. The brain MRI performed at term was analyzed for regional brain volumes. Analyzed IL-6 genotypes did not show statistically significant association with structural brain lesions. However, IL-6 -174 CC and -572 GG genotypes associated with reduced volume of one brain region, the combined volume of basal ganglia and thalami, both in univariate and in multivariate analyses (p = 0.009, 0.009, respectively). The association of IL-6 -174 and -572 genetic polymorphisms with smaller volumes in deep gray matter provides us new ways to understand the processes leading to neurologic impairments in preterm infants.

A comparative study of theoretical graph models for characterizing structural networks of human brain.

PubMed

Li, Xiaojin; Hu, Xintao; Jin, Changfeng; Han, Junwei; Liu, Tianming; Guo, Lei; Hao, Wei; Li, Lingjiang

2013-01-01

Previous studies have investigated both structural and functional brain networks via graph-theoretical methods. However, there is an important issue that has not been adequately discussed before: what is the optimal theoretical graph model for describing the structural networks of human brain? In this paper, we perform a comparative study to address this problem. Firstly, large-scale cortical regions of interest (ROIs) are localized by recently developed and validated brain reference system named Dense Individualized Common Connectivity-based Cortical Landmarks (DICCCOL) to address the limitations in the identification of the brain network ROIs in previous studies. Then, we construct structural brain networks based on diffusion tensor imaging (DTI) data. Afterwards, the global and local graph properties of the constructed structural brain networks are measured using the state-of-the-art graph analysis algorithms and tools and are further compared with seven popular theoretical graph models. In addition, we compare the topological properties between two graph models, namely, stickiness-index-based model (STICKY) and scale-free gene duplication model (SF-GD), that have higher similarity with the real structural brain networks in terms of global and local graph properties. Our experimental results suggest that among the seven theoretical graph models compared in this study, STICKY and SF-GD models have better performances in characterizing the structural human brain network.

Segmentation of brain structures in presence of a space-occupying lesion.

PubMed

Pollo, Claudio; Cuadra, Meritxell Bach; Cuisenaire, Olivier; Villemure, Jean-Guy; Thiran, Jean-Philippe

2005-02-15

Brain deformations induced by space-occupying lesions may result in unpredictable position and shape of functionally important brain structures. The aim of this study is to propose a method for segmentation of brain structures by deformation of a segmented brain atlas in presence of a space-occupying lesion. Our approach is based on an a priori model of lesion growth (MLG) that assumes radial expansion from a seeding point and involves three steps: first, an affine registration bringing the atlas and the patient into global correspondence; then, the seeding of a synthetic tumor into the brain atlas providing a template for the lesion; finally, the deformation of the seeded atlas, combining a method derived from optical flow principles and a model of lesion growth. The method was applied on two meningiomas inducing a pure displacement of the underlying brain structures, and segmentation accuracy of ventricles and basal ganglia was assessed. Results show that the segmented structures were consistent with the patient's anatomy and that the deformation accuracy of surrounding brain structures was highly dependent on the accurate placement of the tumor seeding point. Further improvements of the method will optimize the segmentation accuracy. Visualization of brain structures provides useful information for therapeutic consideration of space-occupying lesions, including surgical, radiosurgical, and radiotherapeutic planning, in order to increase treatment efficiency and prevent neurological damage.

Critical perspectives on causality and inference in brain networks: Allusions, illusions, solutions?. Comment on: "Foundational perspectives on causality in large-scale brain networks" by M. Mannino and S.L. Bressler

NASA Astrophysics Data System (ADS)

Diwadkar, Vaibhav A.

2015-12-01

The human brain is an impossibly difficult cartographic landscape to map out. Within it's convoluted and labyrinthine structure is folded a million years of phylogeny, somehow expressed in the ontogeny of the specific organism; an ontogeny that conceals idiosyncratic effects of countless genes, and then the (perhaps) countably infinite effects of processes of the organism's lifespan subsequently resulting in remarkable heterogeneity [1,2]. The physical brain itself is therefore a nearly un-decodable ;time machine; motivating more questions than frameworks for answering those questions: Why has evolution endowed it with the general structure that is possesses [3]; Is there regularity in macroscopic metrics of structure across species [4]; What are the most meaningful structural units in the brain: molecules, neurons, cortical columns or cortical maps [5]? Remarkably, understanding the intricacies of structure is perhaps not even the most difficult aspect of understanding the human brain. In fact, and as recently argued, a central issue lies in resolving the dialectic between structure and function: how does dynamic function arises from static (at least at the time scales at which human brain function is experimentally studied) brain structures [6]? In other words, if the mind is the brain ;in action;, how does it arise?

Brain plasticity and motor practice in cognitive aging.

PubMed

Cai, Liuyang; Chan, John S Y; Yan, Jin H; Peng, Kaiping

2014-01-01

For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population.

Long-term treatment with haloperidol affects neuropeptide S and NPSR mRNA levels in the rat brain.

PubMed

Palasz, Artur; Rojczyk, Ewa; Golyszny, Milosz; Filipczyk, Lukasz; Worthington, John J; Wiaderkiewicz, Ryszard

2016-04-01

The brainstem-derived neuropeptide S (NPS) has a multidirectional regulatory activity, especially as a potent anxiolytic factor. Accumulating data suggests that neuroleptics affect peptidergic signalling in various brain structures. However, there is no information regarding the influence of haloperidol on NPS and NPS receptor (NPSR) expression. We assessed NPS and NPSR mRNA levels in brains of rats treated with haloperidol using quantitative real-time polymerase chain reaction. Chronic haloperidol treatment (4 weeks) led to a striking upregulation of NPS and NPSR expression in the rat brainstem. Conversely, the NPSR mRNA expression was decreased in the hippocampus and striatum. This stark increase of NPS in response to haloperidol treatment supports the hypothesis that this neuropeptide is involved in the dopamine-dependent anxiolytic actions of neuroleptics and possibly also in the pathophysiology of mental disorders. Furthermore, our findings underline the complex nature of potential interactions between dopamine receptors and brain peptidergic pathways, which has potential clinical applications.

The serotonin receptor 7 and the structural plasticity of brain circuits

PubMed Central

Volpicelli, Floriana; Speranza, Luisa; di Porzio, Umberto; Crispino, Marianna; Perrone-Capano, Carla

2014-01-01

Serotonin (5-hydroxytryptamine, 5-HT) modulates numerous physiological processes in the nervous system. Together with its function as neurotransmitter, 5-HT regulates neurite outgrowth, dendritic spine shape and density, growth cone motility and synapse formation during development. In the mammalian brain 5-HT innervation is virtually ubiquitous and the diversity and specificity of its signaling and function arise from at least 20 different receptors, grouped in 7 classes. Here we will focus on the role 5-HT7 receptor (5-HT7R) in the correct establishment of neuronal cytoarchitecture during development, as also suggested by its involvement in several neurodevelopmental disorders. The emerging picture shows that this receptor is a key player contributing not only to shape brain networks during development but also to remodel neuronal wiring in the mature brain, thus controlling cognitive and emotional responses. The activation of 5-HT7R might be one of the mechanisms underlying the ability of the CNS to respond to different stimuli by modulation of its circuit configuration. PMID:25309369

Beyond functional architecture in cognitive neuropsychology: a reply to Coltheart (2010).

PubMed

Plaut, David C; Patterson, Karalyn

2010-01-01

We (Patterson & Plaut, 2009) argued that cognitive neuropsychology has had a limited impact on cognitive science due to a nearly exclusive reliance on (a) single-case studies, (b) dissociations in cognitive performance, and (c) shallow, box-and-arrow theorizing, and we advocated adopting a case-series methodology, considering associations as well as dissociations, and employing explicit computational modeling in studying "how the brain does its cognitive business." In reply, Coltheart (2010) claims that our concern is misplaced because cognitive neuropsychology is concerned only with studying the mind, in terms of its "functional architecture," without regard to how this is implemented in the brain. In this response, we do not dispute his characterization of cognitive neuropsychology as it has typically been practiced over the last 40 years, but we suggest that our understanding of brain structure and function has advanced to the point where studying the mind without regard to the brain is unwise and perpetuates the field's isolation. Copyright © 2009 Cognitive Science Society, Inc.

Structure-activity relationship study of vitamin k derivatives yields highly potent neuroprotective agents.

PubMed

Josey, Benjamin J; Inks, Elizabeth S; Wen, Xuejun; Chou, C James

2013-02-14

Historically known for its role in blood coagulation and bone formation, vitamin K (VK) has begun to emerge as an important nutrient for brain function. While VK involvement in the brain has not been fully explored, it is well-known that oxidative stress plays a critical role in neurodegenerative diseases. It was recently reported that VK protects neurons and oligodendrocytes from oxidative injury and rescues Drosophila from mitochondrial defects associated with Parkinson's disease. In this study, we take a chemical approach to define the optimal and minimum pharmacophore responsible for the neuroprotective effects of VK. In doing so, we have developed a series of potent VK analogues with favorable drug characteristics that provide full protection at nanomolar concentrations in a well-defined model of neuronal oxidative stress. Additionally, we have characterized key cellular responses and biomarkers consistent with the compounds' ability to rescue cells from oxidative stress induced cell death.

Atomoxetine restores the response inhibition network in Parkinson’s disease

PubMed Central

Rae, Charlotte L.; Nombela, Cristina; Rodríguez, Patricia Vázquez; Ye, Zheng; Hughes, Laura E.; Jones, P. Simon; Ham, Timothy; Rittman, Timothy; Coyle-Gilchrist, Ian; Regenthal, Ralf; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

2016-01-01

Abstract Parkinson’s disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson’s disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity. Here we tested the hypotheses that atomoxetine can restore functional brain networks for response inhibition in Parkinson’s disease, and that both structural and functional connectivity determine the behavioural effect. In a randomized, double-blind placebo-controlled crossover study, 19 patients with mild-to-moderate idiopathic Parkinson’s disease underwent functional magnetic resonance imaging during a stop-signal task, while on their usual dopaminergic therapy. Patients received 40 mg atomoxetine or placebo, orally. This regimen anticipates that noradrenergic therapies for behavioural symptoms would be adjunctive to, not a replacement for, dopaminergic therapy. Twenty matched control participants provided normative data. Arterial spin labelling identified no significant changes in regional perfusion. We assessed functional interactions between key frontal and subcortical brain areas for response inhibition, by comparing 20 dynamic causal models of the response inhibition network, inverted to the functional magnetic resonance imaging data and compared using random effects model selection. We found that the normal interaction between pre-supplementary motor cortex and the inferior frontal gyrus was absent in Parkinson’s disease patients on placebo (despite dopaminergic therapy), but this connection was restored by atomoxetine. The behavioural change in response inhibition (improvement indicated by reduced stop-signal reaction time) following atomoxetine correlated with structural connectivity as measured by the fractional anisotropy in the white matter underlying the inferior frontal gyrus. Using multiple regression models, we examined the factors that influenced the individual differences in the response to atomoxetine: the reduction in stop-signal reaction time correlated with structural connectivity and baseline performance, while disease severity and drug plasma level predicted the change in fronto-striatal effective connectivity following atomoxetine. These results suggest that (i) atomoxetine increases sensitivity of the inferior frontal gyrus to afferent inputs from the pre-supplementary motor cortex; (ii) atomoxetine can enhance downstream modulation of frontal-subcortical connections for response inhibition; and (iii) the behavioural consequences of treatment are dependent on fronto-striatal structural connections. The individual differences in behavioural responses to atomoxetine highlight the need for patient stratification in future clinical trials of noradrenergic therapies for Parkinson’s disease. PMID:27343257

Multiple sites of extinction for a single learned response

PubMed Central

Mauk, Michael D.

2012-01-01

Most learned responses can be diminished by extinction, a process that can be engaged when a conditioned stimulus (CS) is presented but not reinforced. We present evidence that plasticity in at least two brain regions can mediate extinction of responses produced by trace eyelid conditioning, where the CS and the reinforcing stimulus are separated by a stimulus-free interval. We observed individual differences in the effects of blocking extinction mechanisms in the cerebellum, the structure that, along with several forebrain structures, mediates acquisition of trace eyelid responses; in some rabbits extinction was prevented, whereas in others it was largely unaffected. We also show that cerebellar mechanisms can mediate extinction when noncerebellar mechanisms are bypassed. Together, these observations indicate that trace eyelid responses can be extinguished via processes operating at more than one site, one in the cerebellum and one upstream in forebrain. The relative contributions of these sites may vary from animal to animal and situation to situation. PMID:21940608

Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrP(C)), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution.

PubMed

Calderón-Garcidueñas, Lilian; Cross, Janet V; Franco-Lira, Maricela; Aragón-Flores, Mariana; Kavanaugh, Michael; Torres-Jardón, Ricardo; Chao, Chih-Kai; Thompson, Charles; Chang, Jing; Zhu, Hongtu; D'Angiulli, Amedeo

2013-01-01

Mexico City Metropolitan Area children chronically exposed to high concentrations of air pollutants exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses along with accumulation of misfolded proteins observed in the early stages of Alzheimer and Parkinson's diseases. A complex modulation of serum cytokines and chemokines influences children's brain structural and gray/white matter volumetric responses to air pollution. The search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term is our principal aim. We explored and compared a profile of cytokines, chemokines (Multiplexing LASER Bead Technology) and Cellular prion protein (PrP(C)) in normal cerebro-spinal-fluid (CSF) of urban children with high vs. low air pollution exposures. PrP(C) and macrophage inhibitory factor (MIF) were also measured in serum. Samples from 139 children ages 11.91 ± 4.2 years were measured. Highly exposed children exhibited significant increases in CSF MIF (p = 0.002), IL6 (p = 0.006), IL1ra (p = 0.014), IL-2 (p = 0.04), and PrP(C) (p = 0.039) vs. controls. MIF serum concentrations were higher in exposed children (p = 0.009). Our results suggest CSF as a MIF, IL6, IL1Ra, IL-2, and PrP(C) compartment that can possibly differentiate air pollution exposures in children. MIF, a key neuro-immune mediator, is a potential biomarker bridge to identify children with CNS inflammation. Fine tuning of immune-to-brain communication is crucial to neural networks appropriate functioning, thus the short and long term effects of systemic inflammation and dysregulated neural immune responses are of deep concern for millions of exposed children. Defining the linkage and the health consequences of the brain / immune system interactions in the developing brain chronically exposed to air pollutants ought to be of pressing importance for public health.

Changes of brain response induced by simulated weightlessness

NASA Astrophysics Data System (ADS)

Wei, Jinhe; Yan, Gongdong; Guan, Zhiqiang

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

Dissociations between behavioural and functional magnetic resonance imaging-based evaluations of cognitive function after brain injury

PubMed Central

Bardin, Jonathan C.; Fins, Joseph J.; Katz, Douglas I.; Hersh, Jennifer; Heier, Linda A.; Tabelow, Karsten; Dyke, Jonathan P.; Ballon, Douglas J.; Schiff, Nicholas D.

2011-01-01

Functional neuroimaging methods hold promise for the identification of cognitive function and communication capacity in some severely brain-injured patients who may not retain sufficient motor function to demonstrate their abilities. We studied seven severely brain-injured patients and a control group of 14 subjects using a novel hierarchical functional magnetic resonance imaging assessment utilizing mental imagery responses. Whereas the control group showed consistent and accurate (for communication) blood-oxygen-level-dependent responses without exception, the brain-injured subjects showed a wide variation in the correlation of blood-oxygen-level-dependent responses and overt behavioural responses. Specifically, the brain-injured subjects dissociated bedside and functional magnetic resonance imaging-based command following and communication capabilities. These observations reveal significant challenges in developing validated functional magnetic resonance imaging-based methods for clinical use and raise interesting questions about underlying brain function assayed using these methods in brain-injured subjects. PMID:21354974

Patterns of Individual Variation in Visual Pathway Structure and Function in the Sighted and Blind

PubMed Central

Datta, Ritobrato; Benson, Noah C.; Prasad, Sashank; Jacobson, Samuel G.; Cideciyan, Artur V.; Bridge, Holly; Watkins, Kate E.; Butt, Omar H.; Dain, Aleksandra S.; Brandes, Lauren; Gennatas, Efstathios D.

2016-01-01

Many structural and functional brain alterations accompany blindness, with substantial individual variation in these effects. In normally sighted people, there is correlated individual variation in some visual pathway structures. Here we examined if the changes in brain anatomy produced by blindness alter the patterns of anatomical variation found in the sighted. We derived eight measures of central visual pathway anatomy from a structural image of the brain from 59 sighted and 53 blind people. These measures showed highly significant differences in mean size between the sighted and blind cohorts. When we examined the measurements across individuals within each group we found three clusters of correlated variation, with V1 surface area and pericalcarine volume linked, and independent of the thickness of V1 cortex. These two clusters were in turn relatively independent of the volumes of the optic chiasm and lateral geniculate nucleus. This same pattern of variation in visual pathway anatomy was found in the sighted and the blind. Anatomical changes within these clusters were graded by the timing of onset of blindness, with those subjects with a post-natal onset of blindness having alterations in brain anatomy that were intermediate to those seen in the sighted and congenitally blind. Many of the blind and sighted subjects also contributed functional MRI measures of cross-modal responses within visual cortex, and a diffusion tensor imaging measure of fractional anisotropy within the optic radiations and the splenium of the corpus callosum. We again found group differences between the blind and sighted in these measures. The previously identified clusters of anatomical variation were also found to be differentially related to these additional measures: across subjects, V1 cortical thickness was related to cross-modal activation, and the volume of the optic chiasm and lateral geniculate was related to fractional anisotropy in the visual pathway. Our findings show that several of the structural and functional effects of blindness may be reduced to a smaller set of dimensions. It also seems that the changes in the brain that accompany blindness are on a continuum with normal variation found in the sighted. PMID:27812129

Functional brain networks reconstruction using group sparsity-regularized learning.

PubMed

Zhao, Qinghua; Li, Will X Y; Jiang, Xi; Lv, Jinglei; Lu, Jianfeng; Liu, Tianming

2018-06-01

Investigating functional brain networks and patterns using sparse representation of fMRI data has received significant interests in the neuroimaging community. It has been reported that sparse representation is effective in reconstructing concurrent and interactive functional brain networks. To date, most of data-driven network reconstruction approaches rarely take consideration of anatomical structures, which are the substrate of brain function. Furthermore, it has been rarely explored whether structured sparse representation with anatomical guidance could facilitate functional networks reconstruction. To address this problem, in this paper, we propose to reconstruct brain networks utilizing the structure guided group sparse regression (S2GSR) in which 116 anatomical regions from the AAL template, as prior knowledge, are employed to guide the network reconstruction when performing sparse representation of whole-brain fMRI data. Specifically, we extract fMRI signals from standard space aligned with the AAL template. Then by learning a global over-complete dictionary, with the learned dictionary as a set of features (regressors), the group structured regression employs anatomical structures as group information to regress whole brain signals. Finally, the decomposition coefficients matrix is mapped back to the brain volume to represent functional brain networks and patterns. We use the publicly available Human Connectome Project (HCP) Q1 dataset as the test bed, and the experimental results indicate that the proposed anatomically guided structure sparse representation is effective in reconstructing concurrent functional brain networks.

Beyond sex differences: new approaches for thinking about variation in brain structure and function

PubMed Central

Joel, Daphna; Fausto-Sterling, Anne

2016-01-01

In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being. PMID:26833844

Modulation of GABA receptors expressed in Xenopus oocytes by 13-L-hydroxylinoleic acid and food additives.

PubMed

Aoshima, H; Tenpaku, Y

1997-12-01

To study the effects of 13-L-hydroxylinoleic acid (LOH) and food additives on gamma-aminobutyric acid (GABA) receptors, ionotropic GABA receptors were expressed in Xenopus oocytes by injecting mRNAs prepared from rat whole brain. LOH, which was prepared by reduction of 13-L-hydroperoxylinoleic acid (LOOH), inhibited the response of GABA receptors in the presence of high concentrations of GABA. LOH also inhibited nicotinic acetylcholine, glycine, and kainate receptors, while it had little effect on NMDA receptors expressed in Xenopus oocytes. However, LOH potentiated the response of GABA receptors as well as LOOH in the presence of low concentrations of GABA, possibly increasing the affinity of GABA for the receptors, while linoleic acid did not. Since some modification of the compounds seemed to change their effects on GABA receptors, the responses of GABA receptors elicited by 10 microM GABA were measured in the presence of compounds with various kinds of functional groups or the structural isomers of pentanol. Potentiation of GABA receptors depended strongly on the species of functional groups and also depended on the structure of the isomers. Then effects of various kinds of food additives on GABA receptors were also examined; perfumes such as alcohols or esters potentiated the responses strongly, while hexylamine, nicotinamide, or caffeine inhibited the responses, mainly in a competitive manner, and vanillin inhibited the responses noncompetitively. These results suggest the possibility that production of LOOH and LOH, or intake of much of some food additives, modulates the neural transmission in the brain, especially through ionotropic GABA receptors and changes the frame of the human mind, as alcohol or tobacco does.

MR Anatomy of Deep Brain Nuclei with Special Reference to Specific Diseases and Deep Brain Stimulation Localization

PubMed Central

Telford, Ryan; Vattoth, Surjith

2014-01-01

Summary Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures. PMID:24571832

Effects of leptin deficiency and replacement on cerebellar response to food-related cues

PubMed Central

Berman, Steven M.; Paz-Filho, Gilberto; Wong, Ma-Li; Kohno, Milky; Licinio, Julio; London, Edythe D.

2013-01-01

Leptin affects eating behavior partly by altering the response of the brain to food-related stimuli. Effects of leptin on brain structure have been observed in the cerebellum, where leptin receptors are most densely expressed, but the function of leptin in the cerebellum remains unclear. We performed a nonrandomized, prospective interventional study of three adults with genetically-mediated leptin deficiency. FMRI was recorded three times each year during years 5 and 6 of leptin replacement treatment. Session one of each year occurred after 10 months of continuous daily replacement, session two after 33–37 days without leptin, and session three 14–23 days after daily replacement was restored. Statistical parametric mapping software (SPM5) was employed to contrast the fMRI blood-oxygenation level-dependent response to images of high-calorie foods versus images of brick walls. Covariate analyses quantified the effects of the duration of leptin replacement and concomitant changes in body mass on the cerebral responses. Longer duration of replacement was associated with more activation by food images in a ventral portion of the posterior lobe of the cerebellum, while simultaneous decreases in body mass were associated with decreased activation in a more dorsal portion of the same lobe. These findings indicate that leptin replacement reversibly alters neural function within the posterior cerebellum, and modulates plasticity-dependent brain physiology in response to food cues. The results suggest an underexplored role for the posterior cerebellum in the regulation of leptin-mediated processes related to food intake. PMID:22576622

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

PubMed Central

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

2008-01-01

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

Plasticity in the Human Visual Cortex: An Ophthalmology-Based Perspective

PubMed Central

Rosa, Andreia Martins; Silva, Maria Fátima; Murta, Joaquim

2013-01-01

Neuroplasticity refers to the ability of the brain to reorganize the function and structure of its connections in response to changes in the environment. Adult human visual cortex shows several manifestations of plasticity, such as perceptual learning and adaptation, working under the top-down influence of attention. Plasticity results from the interplay of several mechanisms, including the GABAergic system, epigenetic factors, mitochondrial activity, and structural remodeling of synaptic connectivity. There is also a downside of plasticity, that is, maladaptive plasticity, in which there are behavioral losses resulting from plasticity changes in the human brain. Understanding plasticity mechanisms could have major implications in the diagnosis and treatment of ocular diseases, such as retinal disorders, cataract and refractive surgery, amblyopia, and in the evaluation of surgical materials and techniques. Furthermore, eliciting plasticity could open new perspectives in the development of strategies that trigger plasticity for better medical and surgical outcomes. PMID:24205505

Biological Risk for the Development of Problem Behavior in Adolescence: Integrating Insights from Behavioral Genetics and Neuroscience.

PubMed

Harden, K Paige; Mann, Frank D

2015-12-01

Adolescence is a time of increasing engagement in a variety of problem behaviors, including substance use and delinquency. Genetic risk for problem behavior increases over adolescence, is mediated partially by individual differences in sensation seeking, and is exacerbated by involvement with deviant peers. In this article, we describe how findings from behavioral genetic research on problem behavior intersect with research from developmental neuroscience. In particular, the incentive-processing system, including the ventral striatum, responds increasingly to rewards in adolescence, particularly in peer contexts. This developmental shift may be influenced by hormonal changes at puberty. Individual differences in the structure and function of reward-responsive brain regions may be intermediary phenotypes that mediate adolescents' genetic risk for problem behavior. The study of problem behavior can be enriched by interdisciplinary research that integrates measures of brain structure and function into genetically informed studies.

Cliques of Neurons Bound into Cavities Provide a Missing Link between Structure and Function.

PubMed

Reimann, Michael W; Nolte, Max; Scolamiero, Martina; Turner, Katharine; Perin, Rodrigo; Chindemi, Giuseppe; Dłotko, Paweł; Levi, Ran; Hess, Kathryn; Markram, Henry

2017-01-01

The lack of a formal link between neural network structure and its emergent function has hampered our understanding of how the brain processes information. We have now come closer to describing such a link by taking the direction of synaptic transmission into account, constructing graphs of a network that reflect the direction of information flow, and analyzing these directed graphs using algebraic topology. Applying this approach to a local network of neurons in the neocortex revealed a remarkably intricate and previously unseen topology of synaptic connectivity. The synaptic network contains an abundance of cliques of neurons bound into cavities that guide the emergence of correlated activity. In response to stimuli, correlated activity binds synaptically connected neurons into functional cliques and cavities that evolve in a stereotypical sequence toward peak complexity. We propose that the brain processes stimuli by forming increasingly complex functional cliques and cavities.

Brain Responses to Contrastive and Noncontrastive Morphosyntactic Structures in African American English and Mainstream American English: ERP Evidence for the Neural Indices of Dialect

ERIC Educational Resources Information Center

Garcia, Felicidad M.

2017-01-01

Recent research has shown that distinct event-related potential (ERP) signatures are associated with switching between languages compared to switching between dialects or registers (e.g., Khamis-Dakwar & Froud, 2007; Moreno, Federmeier & Kutas, 2002). The current investigation builds on these findings to examine whether contrastive and…

Advancing multiscale structural mapping of the brain through fluorescence imaging and analysis across length scales

PubMed Central

Hogstrom, L. J.; Guo, S. M.; Murugadoss, K.; Bathe, M.

2016-01-01

Brain function emerges from hierarchical neuronal structure that spans orders of magnitude in length scale, from the nanometre-scale organization of synaptic proteins to the macroscopic wiring of neuronal circuits. Because the synaptic electrochemical signal transmission that drives brain function ultimately relies on the organization of neuronal circuits, understanding brain function requires an understanding of the principles that determine hierarchical neuronal structure in living or intact organisms. Recent advances in fluorescence imaging now enable quantitative characterization of neuronal structure across length scales, ranging from single-molecule localization using super-resolution imaging to whole-brain imaging using light-sheet microscopy on cleared samples. These tools, together with correlative electron microscopy and magnetic resonance imaging at the nanoscopic and macroscopic scales, respectively, now facilitate our ability to probe brain structure across its full range of length scales with cellular and molecular specificity. As these imaging datasets become increasingly accessible to researchers, novel statistical and computational frameworks will play an increasing role in efforts to relate hierarchical brain structure to its function. In this perspective, we discuss several prominent experimental advances that are ushering in a new era of quantitative fluorescence-based imaging in neuroscience along with novel computational and statistical strategies that are helping to distil our understanding of complex brain structure. PMID:26855758

A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses.

PubMed

Jensen, Karin B; Kaptchuk, Ted J; Chen, Xiaoyan; Kirsch, Irving; Ingvar, Martin; Gollub, Randy L; Kong, Jian

2015-10-01

Fundamental aspects of human behavior operate outside of conscious awareness. Yet, theories of conditioned responses in humans, such as placebo and nocebo effects on pain, have a strong emphasis on conscious recognition of contextual cues that trigger the response. Here, we investigated the neural pathways involved in nonconscious activation of conditioned pain responses, using functional magnetic resonance imaging in healthy participants. Nonconscious compared with conscious activation of conditioned placebo analgesia was associated with increased activation of the orbitofrontal cortex, a structure with direct connections to affective brain regions and basic reward processing. During nonconscious nocebo, there was increased activation of the thalamus, amygdala, and hippocampus. In contrast to previous assumptions about conditioning in humans, our results show that conditioned pain responses can be elicited independently of conscious awareness and our results suggest a hierarchical activation of neural pathways for nonconscious and conscious conditioned responses. Demonstrating that the human brain has a nonconscious mechanism for responding to conditioned cues has major implications for the role of associative learning in behavioral medicine and psychiatry. Our results may also open up for novel approaches to translational animal-to-human research since human consciousness and animal cognition is an inherent paradox in all behavioral science. © The Author 2014. Published by Oxford University Press.

Random Forest Segregation of Drug Responses May Define Regions of Biological Significance

PubMed Central

Bukhari, Qasim; Borsook, David; Rudin, Markus; Becerra, Lino

2016-01-01

The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF) method to detect differences in the pharmacological MRI (phMRI) response in rats to treatment with an analgesic drug (buprenorphine) as compared to control (saline). Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD), and high dose (HD), and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups. RF analysis was able to identify drug effects based on differential phMRI responses in the hippocampus, amygdala, nucleus accumbens, superior colliculus, and the lateral and posterior thalamus for drug vs. saline. These structures have high levels of mu opioid receptors. In addition these regions are involved in aversive signaling, which is inhibited by mu opioids. The results demonstrate that buprenorphine mediated phMRI responses comprise characteristic features that allow a supervised differentiation from placebo treated rats as well as the proper allocation to the respective drug dose group using the RF method, a method that has been successfully applied in clinical studies. PMID:27014046

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

PubMed

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

2006-03-31

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

SU-D-207A-04: Use of Gradient Echo Plural Contrast Imaging (GEPCI) in MR-Guided Radiation Therapy: A Feasibility Study Targeting Brain Treatment

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

Cai, B; Rao, Y; Tsien, C

Purpose: To implement the Gradient Echo Plural Contrast Imaging(GEPCI) technique in MRI-simulation for radiation therapy and assess the feasibility of using GEPCI images with advanced inhomogeneity correction in MRI-guided radiotherapy for brain treatment. Methods: An optimized multigradient-echo GRE sequence (TR=50ms;TE1=4ms;delta-TE=4ms;flip angle=300,11 Echoes) was developed to generate both structural (T1w and T2*w) and functional MRIs (field and susceptibility maps) from a single acquisition. One healthy subject (Subject1) and one post-surgical brain cancer patient (Subject2) were scanned on a Philips Ingenia 1.5T MRI used for radiation therapy simulation. Another healthy subject (Subject3) was scanned on a 0.35T MRI-guided radiotherapy (MR-IGRT) system (ViewRay).more » A voxel spread function (VSF) was used to correct the B0 inhomogeneities caused by surgical cavities and edema for Subject2. GEPCI images and standard radiotherapy planning MRIs for this patient were compared focusing the delineation of radiotherapy target region. Results: GEPCI brain images were successfully derived from all three subjects with scan times of <7 minutes. The images derived for Subjects1&2 demonstrated that GEPCI can be applied and combined into radiotherapy MRI simulation. Despite low field, T1-weighted and R2* images were successfully reconstructed for Subject3 and were satisfactory for contour and target delineation. The R2* distribution of grey matter (center=12,FWHM=4.5) and white matter (center=14.6, FWHM=2) demonstrated the feasibility for tissue segmentation and quantification. The voxel spread function(VSF) corrected surgical site related inhomogeneities for Subject2. R2* and quantitative susceptibility map(QSM) images for Subject2 can be used to quantitatively assess the brain structure response to radiation over the treatment course. Conclusion: We implemented the GEPCI technique in MRI-simulation and in MR-IGRT system for radiation therapy. The images demonstrated that it is feasible to adopt this technique in radiotherapy for structural delineation. The preliminary data also enable the opportunity for quantitative assessment of radiation response of the target region and normal tissue.« less

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

PubMed

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

2017-01-03

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

Representation of the verb's argument-structure in the human brain

PubMed Central

Assadollahi, Ramin; Rockstroh, Brigitte S

2008-01-01

Background A verb's argument structure defines the number and relationships of participants needed for a complete event. One-argument (intransitive) verbs require only a subject to make a complete sentence, while two- and three-argument verbs (transitives and ditransitives) normally take direct and indirect objects. Cortical responses to verbs embedded into sentences (correct or with syntactic violations) indicate the processing of the verb's argument structure in the human brain. The two experiments of the present study examined whether and how this processing is reflected in distinct spatio-temporal cortical response patterns to isolated verbs and/or verbs presented in minimal context. Results The magnetoencephalogram was recorded while 22 native German-speaking adults saw 130 German verbs, presented one at a time for 150 ms each in experiment 1. Verb-evoked electromagnetic responses at 250 – 300 ms after stimulus onset, analyzed in source space, were higher in the left middle temporal gyrus for verbs that take only one argument, relative to two- and three-argument verbs. In experiment 2, the same verbs (presented in different order) were preceded by a proper name specifying the subject of the verb. This produced additional activation between 350 and 450 ms in or near the left inferior frontal gyrus, activity being larger and peaking earlier for one-argument verbs that required no further arguments to form a complete sentence. Conclusion Localization of sources of activity suggests that the activation in temporal and frontal regions varies with the degree by which representations of an event as a part of the verbs' semantics are completed during parsing. PMID:18644141

Stress (hypothalamic-pituitary-adrenal axis) and pain response in male rats exposed lifelong to high vs. low phytoestrogen diets.

PubMed

Lephart, Edwin D; Galindo, Edwardo; Bu, Li Hong

2003-05-15

Estrogens exhibit complex but beneficial effects on brain structure, function and behavior. Soy-derived dietary phytoestrogens protect against hormone-dependent and age-related diseases, due to their estrogen-like hormonal actions. However, the effects of phytoestrogens on brain and behavior are relatively unknown. This study examined the influence of exposing male Long-Evans rats (lifelong) to either a phytoestrogen-rich (Phyto-600) or a phytoestrogen-free (Phyto-free) diet on body weights, behavioral pain thresholds, the hypothalamic-pituitary-adrenal (HPA) hormonal stress response, hippocampal glucocorticoid receptor and brain neural cell adhesion molecules (NCAM) and synaptophysin levels using standard behavioral and biochemical techniques. Body weights were significantly decreased in Phyto-600 fed animals compared to Phyto-free values. There were no significant changes in behavioral pain thresholds, circulating corticosterone concentrations (after acute immobilization stress) or NCAM and synaptophysin levels in various brain regions by the diet treatments. However, Phyto-600 fed males displayed significantly higher plasma adrenocorticotrophin (ACTH) (post-stress) and hippocampal glucocorticoid receptor levels vs. Phyto-free values. These data suggest that (1) body weights are significantly reduced by soy-derived phytoestrogens, (2) behavioral pain thresholds (via heat stimuli) are not influenced by dietary phytoestrogens, but (3) these estrogenic molecules in the hippocampus enhance glucocorticoid receptor abundance and alter the negative feedback of stress hormones towards a female-like pattern of higher ACTH release after activation of the HPA stress axis. This study is the first to show that lifelong consumption of dietary phytoestrogens alters the HPA stress response in male rats.

Nonconscious attention bias to threat is correlated with anterior cingulate cortex gray matter volume: a voxel-based morphometry result and replication.

PubMed

Carlson, Joshua M; Beacher, Felix; Reinke, Karen S; Habib, Reza; Harmon-Jones, Eddie; Mujica-Parodi, Lilianne R; Hajcak, Greg

2012-01-16

An important aspect of the fear response is the allocation of spatial attention toward threatening stimuli. This response is so powerful that modulations in spatial attention can occur automatically without conscious awareness. Functional neuroimaging research suggests that the amygdala and anterior cingulate cortex (ACC) form a network involved in the rapid orienting of attention to threat. A hyper-responsive attention bias to threat is a common component of anxiety disorders. Yet, little is known of how individual differences in underlying brain morphometry relate to variability in attention bias to threat. Here, we performed two experiments using dot-probe tasks that measured individuals' attention bias to backward masked fearful faces. We collected whole-brain structural magnetic resonance images and used voxel-based morphometry to measure brain morphometry. We tested the hypothesis that reduced gray matter within the amygdala and ACC would be associated with reduced attention bias to threat. In Experiment 1, we found that backward masked fearful faces captured spatial attention and that elevated attention bias to masked threat was associated with greater ACC gray matter volumes. In Experiment 2, this association was replicated in a separate sample. Thus, we provide initial and replicating evidence that ACC gray matter volume is correlated with biased attention to threat. Importantly, we demonstrate that variability in affective attention bias within the healthy population is associated with ACC morphometry. This result opens the door for future research into the underlying brain morphometry associated with attention bias in clinically anxious populations. Copyright © 2011 Elsevier Inc. All rights reserved.

Risk and protective factors for structural brain ageing in the eighth decade of life.

PubMed

Ritchie, Stuart J; Tucker-Drob, Elliot M; Cox, Simon R; Dickie, David Alexander; Del C Valdés Hernández, Maria; Corley, Janie; Royle, Natalie A; Redmond, Paul; Muñoz Maniega, Susana; Pattie, Alison; Aribisala, Benjamin S; Taylor, Adele M; Clarke, Toni-Kim; Gow, Alan J; Starr, John M; Bastin, Mark E; Wardlaw, Joanna M; Deary, Ian J

2017-11-01

Individuals differ markedly in brain structure, and in how this structure degenerates during ageing. In a large sample of human participants (baseline n = 731 at age 73 years; follow-up n = 488 at age 76 years), we estimated the magnitude of mean change and variability in changes in MRI measures of brain macrostructure (grey matter, white matter, and white matter hyperintensity volumes) and microstructure (fractional anisotropy and mean diffusivity from diffusion tensor MRI). All indices showed significant average change with age, with considerable heterogeneity in those changes. We then tested eleven socioeconomic, physical, health, cognitive, allostatic (inflammatory and metabolic), and genetic variables for their value in predicting these differences in changes. Many of these variables were significantly correlated with baseline brain structure, but few could account for significant portions of the heterogeneity in subsequent brain change. Physical fitness was an exception, being correlated both with brain level and changes. The results suggest that only a subset of correlates of brain structure are also predictive of differences in brain ageing.

Human Fetal Brain Connectome: Structural Network Development from Middle Fetal Stage to Birth

PubMed Central

Song, Limei; Mishra, Virendra; Ouyang, Minhui; Peng, Qinmu; Slinger, Michelle; Liu, Shuwei; Huang, Hao

2017-01-01

Complicated molecular and cellular processes take place in a spatiotemporally heterogeneous and precisely regulated pattern in the human fetal brain, yielding not only dramatic morphological and microstructural changes, but also macroscale connectomic transitions. As the underlying substrate of the fetal brain structural network, both dynamic neuronal migration pathways and rapid developing fetal white matter (WM) fibers could fundamentally reshape early fetal brain connectome. Quantifying structural connectome development can not only shed light on the brain reconfiguration in this critical yet rarely studied developmental period, but also reveal alterations of the connectome under neuropathological conditions. However, transition of the structural connectome from the mid-fetal stage to birth is not yet known. The contribution of different types of neural fibers to the structural network in the mid-fetal brain is not known, either. In this study, diffusion tensor magnetic resonance imaging (DT-MRI or DTI) of 10 fetal brain specimens at the age of 20 postmenstrual weeks (PMW), 12 in vivo brains at 35 PMW, and 12 in vivo brains at term (40 PMW) were acquired. The structural connectome of each brain was established with evenly parcellated cortical regions as network nodes and traced fiber pathways based on DTI tractography as network edges. Two groups of fibers were categorized based on the fiber terminal locations in the cerebral wall in the 20 PMW fetal brains. We found that fetal brain networks become stronger and more efficient during 20–40 PMW. Furthermore, network strength and global efficiency increase more rapidly during 20–35 PMW than during 35–40 PMW. Visualization of the whole brain fiber distribution by the lengths suggested that the network reconfiguration in this developmental period could be associated with a significant increase of major long association WM fibers. In addition, non-WM neural fibers could be a major contributor to the structural network configuration at 20 PMW and small-world network organization could exist as early as 20 PMW. These findings offer a preliminary record of the fetal brain structural connectome maturation from the middle fetal stage to birth and reveal the critical role of non-WM neural fibers in structural network configuration in the middle fetal stage. PMID:29081731

Social inclusion enhances biological motion processing: A functional near-infrared spectroscopy study

PubMed Central

Bolling, Danielle Z.; Pelphrey, Kevin A.; Kaiser, Martha D.

2012-01-01

Humans are especially tuned to the movements of other people. Neural correlates of this social attunement have been proposed to lie in and around the right posterior superior temporal sulcus (STS) region, which robustly responds to biological motion in contrast to a variety of non-biological motions. This response persists even when no form information is provided, as in point-light displays (PLDs). The aim of the current study was to assess the ability of functional near-infrared spectroscopy (fNIRS) to reliably measure brain responses to PLDs of biological motion, and determine the sensitivity of these responses to interpersonal contextual factors. To establish reliability, we measured brain activation to biological motion with fNIRS and functional magnetic resonance imaging (fMRI) during two separate sessions in an identical group of 12 participants. To establish sensitivity, brain responses to biological motion measured with fNIRS were subjected to an additional social manipulation where participants were either socially included or excluded before viewing PLDs of biological motion. Results revealed comparable brain responses to biological motion using fMRI and fNIRS in the right supramarginal gyrus. Further, social inclusion increased brain responses to biological motion in right supramarginal gyrus and posterior STS. Thus, fNIRS can reliably measure brain responses to biological motion and can detect social experience-dependent modulations of these brain responses. PMID:22941501

Population variation in neuroendocrine activity is associated with behavioral inhibition and hemispheric brain structure in young rhesus monkeys

PubMed Central

Short, Sarah J.; Lubach, Gabriele R.; Shirtcliff, Elizabeth A.; Styner, Martin A.; Gilmore, John H.; Coe, Christopher L.

2014-01-01

Summary Population variation in hypothalamic-pituitary-adrenal (HPA) activity and reactivity was assessed in a healthy sample of 48 juvenile rhesus monkeys. Cluster analysis of the HPA profiles revealed four distinct neuroendocrine phenotypes based on six indices of HPA functioning. Behavioral reactivity was also evaluated in response to novel stimuli, and revealed marked differences between animals in the highest- and lowest-cortisol clusters. Specifically, animals in the high-cortisol cluster showed larger stress-induced cortisol responses and blunted feedback sensitivity to dexamethasone. They were also emotionally reactive, displayed more aggressive behaviors, and were less likely to approach novel objects. In contrast, monkeys in the low-cortisol cluster were more likely to approach and explore novel objects. Representative animals with high or low cortisol profiles were scanned with Magnetic Resonance Imaging to evaluate structural differences in global and regional gray matter (GM) and white matter (WM) volumes. Monkeys with higher cortisol reactivity evinced less hemispheric brain asymmetry, due to decreased GM in the right hemisphere. Stress reactivity was inversely related to global GM and positively related to total cerebrospinal fluid volume. This inverse relationship was also observed in several stress-sensitive regions, including prefrontal and frontal cortices. Our study demonstrates that population variation in pituitary-adrenal activity is related to behavioral disposition and cerebral structure in this nonhuman primate species. PMID:24954302

Rapid brain MRI acquisition techniques at ultra-high fields

PubMed Central

Setsompop, Kawin; Feinberg, David A.; Polimeni, Jonathan R.

2017-01-01

Ultra-high-field MRI provides large increases in signal-to-noise ratio as well as enhancement of several contrast mechanisms in both structural and functional imaging. Combined, these gains result in a substantial boost in contrast-to-noise ratio that can be exploited for higher spatial resolution imaging to extract finer-scale information about the brain. With increased spatial resolution, however, is a concurrent increased image encoding burden that can cause unacceptably long scan times for structural imaging and slow temporal sampling of the hemodynamic response in functional MRI—particularly when whole-brain imaging is desired. To address this issue, new directions of imaging technology development—such as the move from conventional 2D slice-by-slice imaging to more efficient Simultaneous MultiSlice (SMS) or MultiBand imaging (which can be viewed as “pseudo-3D” encoding) as well as full 3D imaging—have provided dramatic improvements in acquisition speed. Such imaging paradigms provide higher SNR efficiency as well as improved encoding efficiency. Moreover, SMS and 3D imaging can make better use of coil sensitivity information in multi-channel receiver arrays used for parallel imaging acquisitions through controlled aliasing in multiple spatial directions. This has enabled unprecedented acceleration factors of an order of magnitude or higher in these imaging acquisition schemes, with low image artifact levels and high SNR. Here we review the latest developments of SMS and 3D imaging methods and related technologies at ultra-high field for rapid high-resolution functional and structural imaging of the brain. PMID:26835884

Far-field brainstem responses evoked by vestibular and auditory stimuli exhibit increases in interpeak latency as brain temperature is decreased

NASA Technical Reports Server (NTRS)

Hoffman, L. F.; Horowitz, J. M.

1984-01-01

The effect of decreasing of brain temperature on the brainstem auditory evoked response (BAER) in rats was investigated. Voltage pulses, applied to a piezoelectric crystal attached to the skull, were used to evoke stimuli in the auditory system by means of bone-conducted vibrations. The responses were recorded at 37 C and 34 C brain temperatures. The peaks of the BAER recorded at 34 C were delayed in comparison with the peaks from the 37 C wave, and the later peaks were more delayed than the earlier peaks. These results indicate that an increase in the interpeak latency occurs as the brain temperature is decreased. Preliminary experiments, in which responses to brief angular acceleration were used to measure the brainstem vestibular evoked response (BVER), have also indicated increases in the interpeak latency in response to the lowering of brain temperature.

Integrating Structure to Protein-Protein Interaction Networks That Drive Metastasis to Brain and Lung in Breast Cancer

PubMed Central

Engin, H. Billur; Guney, Emre; Keskin, Ozlem; Oliva, Baldo; Gursoy, Attila

2013-01-01

Blocking specific protein interactions can lead to human diseases. Accordingly, protein interactions and the structural knowledge on interacting surfaces of proteins (interfaces) have an important role in predicting the genotype-phenotype relationship. We have built the phenotype specific sub-networks of protein-protein interactions (PPIs) involving the relevant genes responsible for lung and brain metastasis from primary tumor in breast cancer. First, we selected the PPIs most relevant to metastasis causing genes (seed genes), by using the “guilt-by-association” principle. Then, we modeled structures of the interactions whose complex forms are not available in Protein Databank (PDB). Finally, we mapped mutations to interface structures (real and modeled), in order to spot the interactions that might be manipulated by these mutations. Functional analyses performed on these sub-networks revealed the potential relationship between immune system-infectious diseases and lung metastasis progression, but this connection was not observed significantly in the brain metastasis. Besides, structural analyses showed that some PPI interfaces in both metastasis sub-networks are originating from microbial proteins, which in turn were mostly related with cell adhesion. Cell adhesion is a key mechanism in metastasis, therefore these PPIs may be involved in similar molecular pathways that are shared by infectious disease and metastasis. Finally, by mapping the mutations and amino acid variations on the interface regions of the proteins in the metastasis sub-networks we found evidence for some mutations to be involved in the mechanisms differentiating the type of the metastasis. PMID:24278371

Factor analysis of regional brain activation in bipolar and healthy individuals reveals a consistent modular structure.

PubMed

Fleck, David E; Welge, Jeffrey A; Eliassen, James C; Adler, Caleb M; DelBello, Melissa P; Strakowski, Stephen M

2018-07-01

The neurophysiological substrates of cognition and emotion, as seen with fMRI, are generally explained using modular structures. The present study was designed to probe the modular structure of cognitive-emotional processing in bipolar and healthy individuals using factor analysis and compare the results with current conceptions of the neurophysiology of bipolar disorder. Exploratory factor analysis was used to assess patterns of covariation among brain regions-of-interest activated during the Continuous Performance Task with Emotional and Neutral Distractors in healthy and bipolar individuals without a priori constraints on the number or composition of latent factors. Results indicated a common cognitive-emotional network consisting of prefrontal, medial temporal, limbic, parietal, anterior cingulate and posterior cingulate modules. However, reduced brain activation to emotional stimuli in the frontal, medial temporal and limbic modules was apparent in the bipolar relative to the healthy group, potentially accounting for emotional dysregulation in bipolar disorder. This study is limited by a relatively small sample size recruited at a single site. The results have yet to be validated on a larger independent sample. Although the modular structure of cognitive-emotional processing is similar in bipolar and healthy individuals, activation in response to emotional/neutral cues varies. These findings are not only consistent with recent conceptions of mood regulation in bipolar disorder, but also suggest that regional activation can be considered within tighter modular structures without compromising data interpretation. This demonstration may serve as a template for data reduction in future region-of-interest analyses to increase statistical power. Copyright © 2018 Elsevier B.V. All rights reserved.

Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

PubMed Central

An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

2014-01-01

Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

The Effects of Spaceflight on Neurocognitive Performance: Extent, Longevity, and Neural Bases

NASA Technical Reports Server (NTRS)

Seidler, Rachael D.; Bloomberg, Jacob; Wood, Scott; Mason, Sara; Mulavara, Ajit; Kofman, Igor; De Dios, Yiri; Gadd, Nicole; Stepanyan, Vahagn; Szecsy, Darcy

2017-01-01

Spaceflight effects on gait, balance, & manual motor control have been well studied; some evidence for cognitive deficits. Rodent cortical motor & sensory systems show neural structural alterations with spaceflight. We found extensive changes in behavior, brain structure & brain function following 70 days of HDBR. Specific Aim: Aim 1-Identify changes in brain structure, function, and network integrity as a function of spaceflight and characterize their time course. Aim 2-Specify relationships between structural and functional brain changes and performance and characterize their time course.

The MNESIS model: Memory systems and processes, identity and future thinking.

PubMed

Eustache, Francis; Viard, Armelle; Desgranges, Béatrice

2016-07-01

The Memory NEo-Structural Inter-Systemic model (MNESIS; Eustache and Desgranges, Neuropsychology Review, 2008) is a macromodel based on neuropsychological data which presents an interactive construction of memory systems and processes. Largely inspired by Tulving's SPI model, MNESIS puts the emphasis on the existence of different memory systems in humans and their reciprocal relations, adding new aspects, such as the episodic buffer proposed by Baddeley. The more integrative comprehension of brain dynamics offered by neuroimaging has contributed to rethinking the existence of memory systems. In the present article, we will argue that understanding the concept of memory by dividing it into systems at the functional level is still valid, but needs to be considered in the light of brain imaging. Here, we reinstate the importance of this division in different memory systems and illustrate, with neuroimaging findings, the links that operate between memory systems in response to task demands that constrain the brain dynamics. During a cognitive task, these memory systems interact transiently to rapidly assemble representations and mobilize functions to propose a flexible and adaptative response. We will concentrate on two memory systems, episodic and semantic memory, and their links with autobiographical memory. More precisely, we will focus on interactions between episodic and semantic memory systems in support of 1) self-identity in healthy aging and in brain pathologies and 2) the concept of the prospective brain during future projection. In conclusion, this MNESIS global framework may help to get a general representation of human memory and its brain implementation with its specific components which are in constant interaction during cognitive processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Vertebrate Brain, Evidence of Its Modular Organization and Operating System: Insights into the Brain's Basic Units of Structure, Function, and Operation and How They Influence Neuronal Signaling and Behavior.

PubMed

Baslow, Morris H

2011-01-01

The human brain is a complex organ made up of neurons and several other cell types, and whose role is processing information for use in eliciting behaviors. However, the composition of its repeating cellular units for both structure and function are unresolved. Based on recent descriptions of the brain's physiological "operating system", a function of the tri-cellular metabolism of N-acetylaspartate (NAA) and N-acetylaspartylglutamate (NAAG) for supply of energy, and on the nature of "neuronal words and languages" for intercellular communication, insights into the brain's modular structural and functional units have been gained. In this article, it is proposed that the basic structural unit in brain is defined by its physiological operating system, and that it consists of a single neuron, and one or more astrocytes, oligodendrocytes, and vascular system endothelial cells. It is also proposed that the basic functional unit in the brain is defined by how neurons communicate, and consists of two neurons and their interconnecting dendritic-synaptic-dendritic field. Since a functional unit is composed of two neurons, it requires two structural units to form a functional unit. Thus, the brain can be envisioned as being made up of the three-dimensional stacking and intertwining of myriad structural units which results not only in its gross structure, but also in producing a uniform distribution of binary functional units. Since the physiological NAA-NAAG operating system for supply of energy is repeated in every structural unit, it is positioned to control global brain function.

Adaptation of brain functional and structural networks in aging.

PubMed

Lee, Annie; Ratnarajah, Nagulan; Tuan, Ta Anh; Chen, Shen-Hsing Annabel; Qiu, Anqi

2015-01-01

The human brain, especially the prefrontal cortex (PFC), is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI), and high angular resolution diffusion imaging (HARDI), and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.