Comparison of laterality index of upper and lower limb movement using brain activated fMRI

NASA Astrophysics Data System (ADS)

Harirchian, Mohammad Hossein; Oghabian, Mohammad Ali; Rezvanizadeh, Alireza; Bolandzadeh, Niousha

2008-03-01

Asymmetry of bilateral cerebral function, i.e. laterality, is an important phenomenon in many brain actions such as motor functions. This asymmetry maybe altered in some clinical conditions such as Multiple Sclerosis (MS). The aim of this study was to delineate the laterality differences for upper and lower limbs in healthy subjects to compare this pattern with subjects suffering from MS in advance. Hence 9 Male healthy subjects underwent fMRI assessment, while they were asked to move their limbs in a predetermined pattern. The results showed that hands movement activates the brain with a significant lateralization in pre-motor cortex in comparison with lower limb. Also, dominant hands activate brain more lateralized than the non-dominant hand. In addition, Left basal ganglia were observed to be activated regardless of the hand used, While, These patterns of Brain activation was not detected in lower limbs. We hypothesize that this difference might be attributed to this point that hand is usually responsible for precise and fine voluntary movements, whereas lower limb joints are mainly responsible for locomotion, a function integrating voluntary and automatic bilateral movements.

Brain Activation in Response to Visually Evoked Sexual Arousal in Male-to-Female Transsexuals: 3.0 Tesla Functional Magnetic Resonance Imaging

PubMed Central

Oh, Seok-Kyun; Kim, Gwang-Won; Yang, Jong-Chul; Kim, Seok-Kwun; Kang, Heoung-Keun

2012-01-01

Objective This study used functional magnetic resonance imaging (fMRI) to contrast the differential brain activation patterns in response to visual stimulation with both male and female erotic nude pictures in male-to-female (MTF) transsexuals who underwent a sex reassignment surgery. Materials and Methods A total of nine healthy MTF transsexuals after a sex reassignment surgery underwent fMRI on a 3.0 Tesla MR Scanner. The brain activation patterns were induced by visual stimulation with both male and female erotic nude pictures. Results The sex hormone levels of the postoperative MTF transsexuals were in the normal range of healthy heterosexual females. The brain areas, which were activated by viewing male nude pictures when compared with viewing female nude pictures, included predominantly the cerebellum, hippocampus, putamen, anterior cingulate gyrus, head of caudate nucleus, amygdala, midbrain, thalamus, insula, and body of caudate nucleus. On the other hand, brain activation induced by viewing female nude pictures was predominantly observed in the hypothalamus and the septal area. Conclusion Our findings suggest that distinct brain activation patterns associated with visual sexual arousal in postoperative MTF transsexuals reflect their sexual orientation to males. PMID:22563262

Short-Term Variations in Response Distribution to Cortical Stimulation

ERIC Educational Resources Information Center

Lesser, Ronald P.; Lee, Hyang Woon; Webber, W. R. S.; Prince, Barry; Crone, Nathan E.; Miglioretti, Diana L.

2008-01-01

Patterns of responses in the cerebral cortex can vary, and are influenced by pre-existing cortical function, but it is not known how rapidly these variations can occur in humans. We investigated how rapidly response patterns to electrical stimulation can vary in intact human brain. We also investigated whether the type of functional change…

Perinatal asphyxia exerts lifelong effects on neuronal responsiveness to stress in specific brain regions in the rat.

PubMed

Salchner, Peter; Engidawork, Ephrem; Hoeger, Harald; Lubec, Barbara; Singewald, Nicolas

2003-09-01

Perinatal asphyxia (PA) causes irreversible damage to the brain of newborns and can produce neurologic and behavioral changes later in life. To identify neuronal substrates underlying the effects of PA, we investigated whether and how neuronal responsiveness to an established stress challenge is affected. We used Fos expression as a marker of neuronal activation and examined the pattern of Fos expression in response to acute swim stress in 24-month-old rats exposed to a 20-minute PA insult. Swim stress produced a similar pattern of Fos expression in control and asphyxiated rats in 34 brain areas. Asphyxiated rats displayed a higher number of stress-induced Fos-positive cells in the nucleus of the solitary tract, parabrachial nucleus, periaqueductal gray, paraventricular hypothalamic nucleus, nucleus accumbens, caudate-putamen, and prelimbic cortex. No differences in the Fos response to stress were observed in other regions, including the locus ceruleus, amygdala, hippocampus, or septum. These data provide functional anatomic evidence that PA has lifelong effects on neuronal communication and leads to an abnormal, augmented neuronal responsiveness to stress in specific brain areas, particularly in the main telencephalic target regions of the mesencephalic dopamine projections, as well as in a functionally related set of brain regions associated with autonomic and neuroendocrine regulation.

Keeping their distance? Odor response patterns along the concentration range

PubMed Central

Strauch, Martin; Ditzen, Mathias; Galizia, C. Giovanni

2012-01-01

We investigate the interplay of odor identity and concentration coding in the antennal lobe (AL) of the honeybee Apis mellifera. In this primary olfactory center of the honeybee brain, odors are encoded by the spatio-temporal response patterns of olfactory glomeruli. With rising odor concentration, further glomerular responses are recruited into the patterns, which affects distances between the patterns. Based on calcium-imaging recordings, we found that such pattern broadening renders distances between glomerular response patterns closer to chemical distances between the corresponding odor molecules. Our results offer an explanation for the honeybee's improved odor discrimination performance at higher odor concentrations. PMID:23087621

Principal component analysis of the cytokine and chemokine response to human traumatic brain injury.

PubMed

Helmy, Adel; Antoniades, Chrystalina A; Guilfoyle, Mathew R; Carpenter, Keri L H; Hutchinson, Peter J

2012-01-01

There is a growing realisation that neuro-inflammation plays a fundamental role in the pathology of Traumatic Brain Injury (TBI). This has led to the search for biomarkers that reflect these underlying inflammatory processes using techniques such as cerebral microdialysis. The interpretation of such biomarker data has been limited by the statistical methods used. When analysing data of this sort the multiple putative interactions between mediators need to be considered as well as the timing of production and high degree of statistical co-variance in levels of these mediators. Here we present a cytokine and chemokine dataset from human brain following human traumatic brain injury and use principal component analysis and partial least squares discriminant analysis to demonstrate the pattern of production following TBI, distinct phases of the humoral inflammatory response and the differing patterns of response in brain and in peripheral blood. This technique has the added advantage of making no assumptions about the Relative Recovery (RR) of microdialysis derived parameters. Taken together these techniques can be used in complex microdialysis datasets to summarise the data succinctly and generate hypotheses for future study.

Vocal and visual stimulation, congruence and lateralization affect brain oscillations in interspecies emotional positive and negative interactions.

PubMed

Balconi, Michela; Vanutelli, Maria Elide

2016-01-01

The present research explored the effect of cross-modal integration of emotional cues (auditory and visual (AV)) compared with only visual (V) emotional cues in observing interspecies interactions. The brain activity was monitored when subjects processed AV and V situations, which represented an emotional (positive or negative), interspecies (human-animal) interaction. Congruence (emotionally congruous or incongruous visual and auditory patterns) was also modulated. electroencephalography brain oscillations (from delta to beta) were analyzed and the cortical source localization (by standardized Low Resolution Brain Electromagnetic Tomography) was applied to the data. Frequency band (mainly low-frequency delta and theta) showed a significant brain activity increasing in response to negative compared to positive interactions within the right hemisphere. Moreover, differences were found based on stimulation type, with an increased effect for AV compared with V. Finally, delta band supported a lateralized right dorsolateral prefrontal cortex (DLPFC) activity in response to negative and incongruous interspecies interactions, mainly for AV. The contribution of cross-modality, congruence (incongruous patterns), and lateralization (right DLPFC) in response to interspecies emotional interactions was discussed at light of a "negative lateralized effect."

Cortical encoding and neurophysiological tracking of intensity and pitch cues signaling English stress patterns in native and nonnative speakers.

PubMed

Chung, Wei-Lun; Bidelman, Gavin M

2016-01-01

We examined cross-language differences in neural encoding and tracking of intensity and pitch cues signaling English stress patterns. Auditory mismatch negativities (MMNs) were recorded in English and Mandarin listeners in response to contrastive English pseudowords whose primary stress occurred either on the first or second syllable (i.e., "nocTICity" vs. "NOCticity"). The contrastive syllable stress elicited two consecutive MMNs in both language groups, but English speakers demonstrated larger responses to stress patterns than Mandarin speakers. Correlations between the amplitude of ERPs and continuous changes in the running intensity and pitch of speech assessed how well each language group's brain activity tracked these salient acoustic features of lexical stress. We found that English speakers' neural responses tracked intensity changes in speech more closely than Mandarin speakers (higher brain-acoustic correlation). Findings demonstrate more robust and precise processing of English stress (intensity) patterns in early auditory cortical responses of native relative to nonnative speakers. Copyright © 2016 Elsevier Inc. All rights reserved.

Live imaging of the innate immune response in neonates reveals differential TLR2 dependent activation patterns in sterile inflammation and infection.

PubMed

Lalancette-Hébert, Melanie; Faustino, Joel; Thammisetty, Sai Sampath; Chip, Sophorn; Vexler, Zinaida S; Kriz, Jasna

2017-10-01

Activation of microglial cells in response to brain injury and/or immune stimuli is associated with a marked induction of Toll-like receptors (TLRs). While in adult brain, the contribution of individual TLRs, including TLR2, in pathophysiological cascades has been well established, their role and spatial and temporal induction patterns in immature brain are far less understood. To examine whether infectious stimuli and sterile inflammatory stimuli trigger distinct TLR2-mediated innate immune responses, we used three models in postnatal day 9 (P9) mice, a model of infection induced by systemic endotoxin injection and two models of sterile inflammation, intra-cortical IL-1β injection and transient middle cerebral artery occlusion (tMCAO). We took advantage of a transgenic mouse model bearing the dual reporter system luciferase/GFP under transcriptional control of a murine TLR2 promoter (TLR2-luc-GFP) to visualize the TLR2 response in the living neonatal brain and then determined neuroinflammation, microglial activation and leukocyte infiltration. We show that in physiological postnatal brain development the in vivo TLR2-luc signal undergoes a marked ∼30-fold decline and temporal-spatial changes during the second and third postnatal weeks. We then show that while endotoxin robustly induces the in vivo TLR2-luc signal in the living brain and increases levels of several inflammatory cytokines and chemokines, the in vivo TLR2-luc signal is reduced after both IL-1β and tMCAO and the inflammatory response is muted. Immunofluorescence revealed that microglial cells are the predominant source of TLR2 production during postnatal brain development and in all three neonatal models studied. Flow cytometry revealed developmental changes in CD11b + /CD45 + and CD11b + /Ly6C + cell populations, involvement of cells of the monocyte lineage, but lack of Ly6G + neutrophils or CD3 + cells in acutely injured neonatal brains. Cumulatively, our results suggest distinct TLR2 induction patterns following PAMP and DAMP - mediated inflammation in immature brain. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Whole-brain activity maps reveal stereotyped, distributed networks for visuomotor behavior

PubMed Central

Portugues, Ruben; Feierstein, Claudia E.; Engert, Florian; Orger, Michael B.

2014-01-01

Summary Most behaviors, even simple innate reflexes, are mediated by circuits of neurons spanning areas throughout the brain. However, in most cases, the distribution and dynamics of firing patterns of these neurons during behavior are not known. We imaged activity, with cellular resolution, throughout the whole brains of zebrafish performing the optokinetic response. We found a sparse, broadly distributed network that has an elaborate, but ordered, pattern, with a bilaterally symmetrical organization. Activity patterns fell into distinct clusters reflecting sensory and motor processing. By correlating neuronal responses with an array of sensory and motor variables, we find that the network can be clearly divided into distinct functional modules. Comparing aligned data from multiple fish, we find that the spatiotemporal activity dynamics and functional organization are highly stereotyped across individuals. These experiments reveal, for the first time in a vertebrate, the comprehensive functional architecture of the neural circuits underlying a sensorimotor behavior. PMID:24656252

Rapid Link of Innate Immune Signal to Adaptive Immunity by Brain–Fat Axis

PubMed Central

Kim, Min Soo; Yan, Jingqi; Wu, Wenhe; Zhang, Guo; Zhang, Yalin; Cai, Dongsheng

2015-01-01

Innate immunity signals induced by pathogen/damage-associated molecular patterns are essential for adaptive immune responses, but it is unclear if the brain plays a role in this process. Here we show that while tumor necrosis factor (TNF) quickly increased in the brain of mice following bacterial infection, intra-brain TNF delivery mimicked bacterial infection to rapidly increase peripheral lymphocytes, especially in the spleen and fat. Multiple mouse models revealed that hypothalamic responses to TNF were accountable for this increase of peripheral lymphocytes in response to bacterial infection. Finally, hypothalamic induction of lipolysis was found to mediate the brain's action in promoting this increase in peripheral adaptive immune response. Thus, the brain-fat axis is important for rapidly linking innate immunity to adaptive immunity. PMID:25848866

A SPECT study of language and brain reorganization three years after pediatric brain injury.

PubMed

Chiu Wong, Stephanie B; Chapman, Sandra B; Cook, Lois G; Anand, Raksha; Gamino, Jacquelyn F; Devous, Michael D

2006-01-01

Using single photon emission computed tomography (SPECT), we investigated brain plasticity in children 3 years after sustaining a severe traumatic brain injury (TBI). First, we assessed brain perfusion patterns (i.e., the extent of brain blood flow to regions of the brain) at rest in eight children who suffered severe TBI as compared to perfusion patterns in eight normally developing children. Second, we examined differences in perfusion between children with severe TBI who showed good versus poor recovery in complex discourse skills. Specifically, the children were asked to produce and abstract core meaning for two stories in the form of a lesson. Inconsistent with our predictions, children with severe TBI showed areas of increased perfusion as compared to normally developing controls. Adult studies have shown the reverse pattern with TBI associated with reduced perfusion. With regard to the second aim and consistent with previously identified brain-discourse relations, we found a strong positive association between perfusion in right frontal regions and discourse abstraction abilities, with higher perfusion linked to better discourse outcomes and lower perfusion linked to poorer discourse outcomes. Furthermore, brain-discourse patterns of increased perfusion in left frontal regions were associated with lower discourse abstraction ability. The results are discussed in terms of how brain changes may represent adaptive and maladaptive plasticity. The findings offer direction for future studies of brain plasticity in response to neurocognitive treatments.

Functional magnetic resonance imaging can be used to explore tactile and nociceptive processing in the infant brain

PubMed Central

Williams, Gemma; Fabrizi, Lorenzo; Meek, Judith; Jackson, Deborah; Tracey, Irene; Robertson, Nicola; Slater, Rebeccah; Fitzgerald, Maria

2015-01-01

Aim Despite the importance of neonatal skin stimulation, little is known about activation of the newborn human infant brain by sensory stimulation of the skin. We carried out functional magnetic resonance imaging (fMRI) to assess the feasibility of measuring brain activation to a range of mechanical stimuli applied to the skin of neonatal infants. Methods We studied 19 term infants with a mean age of 13 days. Brain activation was measured in response to brushing, von Frey hair (vFh) punctate stimulation and, in one case, nontissue damaging pinprick stimulation of the plantar surface of the foot. Initial whole brain analysis was followed by region of interest analysis of specific brain areas. Results Distinct patterns of functional brain activation were evoked by brush and vFh punctate stimulation, which were reduced, but still present, under chloral hydrate sedation. Brain activation increased with increasing stimulus intensity. The feasibility of using pinprick stimulation in fMRI studies was established in one unsedated healthy full-term infant. Conclusion Distinct brain activity patterns can be measured in response to different modalities and intensities of skin sensory stimulation in term infants. This indicates the potential for fMRI studies in exploring tactile and nociceptive processing in the infant brain. PMID:25358870

Neural Correlates of Sexual Orientation in Heterosexual, Bisexual, and Homosexual Men

PubMed Central

Safron, Adam; Sylva, David; Klimaj, Victoria; Rosenthal, A. M.; Li, Meng; Walter, Martin; Bailey, J. Michael

2017-01-01

Studies of subjective and genital sexual arousal in monosexual (i.e. heterosexual and homosexual) men have repeatedly found that erotic stimuli depicting men’s preferred sex produce strong responses, whereas erotic stimuli depicting the other sex produce much weaker responses. Inconsistent results have previously been obtained in bisexual men, who have sometimes demonstrated distinctly bisexual responses, but other times demonstrated patterns more similar to those observed in monosexual men. We used fMRI to investigate neural correlates of responses to erotic pictures and videos in heterosexual, bisexual, and homosexual men, ages 25–50. Sixty participants were included in video analyses, and 62 were included in picture analyses. We focused on the ventral striatum (VS), due to its association with incentive motivation. Patterns were consistent with sexual orientation, with heterosexual and homosexual men showing female-favoring and male-favoring responses, respectively. Bisexual men tended to show less differentiation between male and female stimuli. Consistent patterns were observed in the whole brain, including the VS, and also in additional regions such as occipitotemporal, anterior cingulate, and orbitofrontal cortices. This study extends previous findings of gender-specific neural responses in monosexual men, and provides initial evidence for distinct brain activity patterns in bisexual men. PMID:28145518

Neural Correlates of Sexual Orientation in Heterosexual, Bisexual, and Homosexual Men.

PubMed

Safron, Adam; Sylva, David; Klimaj, Victoria; Rosenthal, A M; Li, Meng; Walter, Martin; Bailey, J Michael

2017-02-01

Studies of subjective and genital sexual arousal in monosexual (i.e. heterosexual and homosexual) men have repeatedly found that erotic stimuli depicting men's preferred sex produce strong responses, whereas erotic stimuli depicting the other sex produce much weaker responses. Inconsistent results have previously been obtained in bisexual men, who have sometimes demonstrated distinctly bisexual responses, but other times demonstrated patterns more similar to those observed in monosexual men. We used fMRI to investigate neural correlates of responses to erotic pictures and videos in heterosexual, bisexual, and homosexual men, ages 25-50. Sixty participants were included in video analyses, and 62 were included in picture analyses. We focused on the ventral striatum (VS), due to its association with incentive motivation. Patterns were consistent with sexual orientation, with heterosexual and homosexual men showing female-favoring and male-favoring responses, respectively. Bisexual men tended to show less differentiation between male and female stimuli. Consistent patterns were observed in the whole brain, including the VS, and also in additional regions such as occipitotemporal, anterior cingulate, and orbitofrontal cortices. This study extends previous findings of gender-specific neural responses in monosexual men, and provides initial evidence for distinct brain activity patterns in bisexual men.

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

Vascular Gene Expression in Nonneoplastic and Malignant Brain

PubMed Central

Madden, Stephen L.; Cook, Brian P.; Nacht, Mariana; Weber, William D.; Callahan, Michelle R.; Jiang, Yide; Dufault, Michael R.; Zhang, Xiaoming; Zhang, Wen; Walter-Yohrling, Jennifer; Rouleau, Cecile; Akmaev, Viatcheslav R.; Wang, Clarence J.; Cao, Xiaohong; St. Martin, Thia B.; Roberts, Bruce L.; Teicher, Beverly A.; Klinger, Katherine W.; Stan, Radu-Virgil; Lucey, Brenden; Carson-Walter, Eleanor B.; Laterra, John; Walter, Kevin A.

2004-01-01

Malignant gliomas are uniformly lethal tumors whose morbidity is mediated in large part by the angiogenic response of the brain to the invading tumor. This profound angiogenic response leads to aggressive tumor invasion and destruction of surrounding brain tissue as well as blood-brain barrier breakdown and life-threatening cerebral edema. To investigate the molecular mechanisms governing the proliferation of abnormal microvasculature in malignant brain tumor patients, we have undertaken a cell-specific transcriptome analysis from surgically harvested nonneoplastic and tumor-associated endothelial cells. SAGE-derived endothelial cell gene expression patterns from glioma and nonneoplastic brain tissue reveal distinct gene expression patterns and consistent up-regulation of certain glioma endothelial marker genes across patient samples. We define the G-protein-coupled receptor RDC1 as a tumor endothelial marker whose expression is distinctly induced in tumor endothelial cells of both brain and peripheral vasculature. Further, we demonstrate that the glioma-induced gene, PV1, shows expression both restricted to endothelial cells and coincident with endothelial cell tube formation. As PV1 provides a framework for endothelial cell caveolar diaphragms, this protein may serve to enhance glioma-induced disruption of the blood-brain barrier and transendothelial exchange. Additional characterization of this extensive brain endothelial cell gene expression database will provide unique molecular insights into vascular gene expression. PMID:15277233

Yawn duration predicts brain weight and cortical neuron number in mammals

PubMed Central

Church, Allyson M.; Pelegrino, Anthony J.

2016-01-01

Research indicates that the motor action pattern of yawning functions to promote cortical arousal and state change through enhanced intracranial circulation and brain cooling. Because the magnitude of this response likely corresponds to the degree of neurophysiological change, we hypothesized that interspecies variation in yawn duration would correlate with underlying neurological differences. Using openly accessible data, we show that both the mean and variance in yawn duration are robust predictors of mammalian brain weight and cortical neuron number (ρ-values > 0.9). Consistent with these effects, primates tend to have longer and more variable yawn durations compared with other mammals. Although yawning has long been considered a stereotyped action pattern, these findings reveal substantial variation in this response and highlight the importance of measuring yawn duration in future research. PMID:27703056

Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile.

PubMed

Joules, R; Doyle, O M; Schwarz, A J; O'Daly, O G; Brammer, M; Williams, S C; Mehta, M A

2015-11-01

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been studied in relation to the glutamate hypothesis of schizophrenia and increases dissociation, positive and negative symptom ratings. Ketamine effects brain function through changes in brain activity; these activity patterns can be modulated by pre-treatment of compounds known to attenuate the effects of ketamine on glutamate release. Ketamine also has marked effects on brain connectivity; we predicted that these changes would also be modulated by compounds known to attenuate glutamate release. Here, we perform task-free pharmacological magnetic resonance imaging (phMRI) to investigate the functional connectivity effects of ketamine in the brain and the potential modulation of these effects by pre-treatment of the compounds lamotrigine and risperidone, compounds hypothesised to differentially modulate glutamate release. Connectivity patterns were assessed by combining windowing, graph theory and multivariate Gaussian process classification. We demonstrate that ketamine has a robust effect on the functional connectivity of the human brain compared to saline (87.5 % accuracy). Ketamine produced a shift from a cortically centred, to a subcortically centred pattern of connections. This effect is strongly modulated by pre-treatment with risperidone (81.25 %) but not lamotrigine (43.75 %). Based on the differential effect of these compounds on ketamine response, we suggest the observed connectivity effects are primarily due to NMDAR blockade rather than downstream glutamatergic effects. The connectivity changes contrast with amplitude of response for which no differential effect between pre-treatments was detected, highlighting the necessity of these techniques in forming an informed view of the mechanistic effects of pharmacological compounds in the human brain.

A Bayesian Model of Category-Specific Emotional Brain Responses

PubMed Central

Wager, Tor D.; Kang, Jian; Johnson, Timothy D.; Nichols, Thomas E.; Satpute, Ajay B.; Barrett, Lisa Feldman

2015-01-01

Understanding emotion is critical for a science of healthy and disordered brain function, but the neurophysiological basis of emotional experience is still poorly understood. We analyzed human brain activity patterns from 148 studies of emotion categories (2159 total participants) using a novel hierarchical Bayesian model. The model allowed us to classify which of five categories—fear, anger, disgust, sadness, or happiness—is engaged by a study with 66% accuracy (43-86% across categories). Analyses of the activity patterns encoded in the model revealed that each emotion category is associated with unique, prototypical patterns of activity across multiple brain systems including the cortex, thalamus, amygdala, and other structures. The results indicate that emotion categories are not contained within any one region or system, but are represented as configurations across multiple brain networks. The model provides a precise summary of the prototypical patterns for each emotion category, and demonstrates that a sufficient characterization of emotion categories relies on (a) differential patterns of involvement in neocortical systems that differ between humans and other species, and (b) distinctive patterns of cortical-subcortical interactions. Thus, these findings are incompatible with several contemporary theories of emotion, including those that emphasize emotion-dedicated brain systems and those that propose emotion is localized primarily in subcortical activity. They are consistent with componential and constructionist views, which propose that emotions are differentiated by a combination of perceptual, mnemonic, prospective, and motivational elements. Such brain-based models of emotion provide a foundation for new translational and clinical approaches. PMID:25853490

Decoding the neural signatures of emotions expressed through sound.

PubMed

Sachs, Matthew E; Habibi, Assal; Damasio, Antonio; Kaplan, Jonas T

2018-07-01

Effective social functioning relies in part on the ability to identify emotions from auditory stimuli and respond appropriately. Previous studies have uncovered brain regions engaged by the affective information conveyed by sound. But some of the acoustical properties of sounds that express certain emotions vary remarkably with the instrument used to produce them, for example the human voice or a violin. Do these brain regions respond in the same way to different emotions regardless of the sound source? To address this question, we had participants (N = 38, 20 females) listen to brief audio excerpts produced by the violin, clarinet, and human voice, each conveying one of three target emotions-happiness, sadness, and fear-while brain activity was measured with fMRI. We used multivoxel pattern analysis to test whether emotion-specific neural responses to the voice could predict emotion-specific neural responses to musical instruments and vice-versa. A whole-brain searchlight analysis revealed that patterns of activity within the primary and secondary auditory cortex, posterior insula, and parietal operculum were predictive of the affective content of sound both within and across instruments. Furthermore, classification accuracy within the anterior insula was correlated with behavioral measures of empathy. The findings suggest that these brain regions carry emotion-specific patterns that generalize across sounds with different acoustical properties. Also, individuals with greater empathic ability have more distinct neural patterns related to perceiving emotions. These results extend previous knowledge regarding how the human brain extracts emotional meaning from auditory stimuli and enables us to understand and connect with others effectively. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Role of the Hypothalamic-Pituitary-Adrenal Axis in Developmental Programming of Health and Disease

PubMed Central

Xiong, Fuxia; Zhang, Lubo

2012-01-01

Adverse environments during the fetal and neonatal development period may permanently program physiology and metabolism, and lead to increased risk of diseases in later life. Programming of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key mechanisms that contribute to altered metabolism and response to stress. Programming of the HPA axis often involves epigenetic modification of the glucocorticoid receptor (GR) gene promoter, which influences tissue-specific GR expression patterns and response to stimuli. This review summarizes the current state of research on the HPA axis and programming of health and disease in the adult, focusing on the epigenetic regulation of GR gene expression patterns in response to fetal and neonatal stress. Aberrant GR gene expression patterns in the developing brain may have a significant negative impact on protection of the immature brain against hypoxic-ischemic encephalopathy in the critical period of development during and immediately after birth. PMID:23200813

Appearance Matters: Neural Correlates of Food Choice and Packaging Aesthetics

PubMed Central

Van der Laan, Laura N.; De Ridder, Denise T. D.; Viergever, Max A.; Smeets, Paul A. M.

2012-01-01

Neuro-imaging holds great potential for predicting choice behavior from brain responses. In this study we used both traditional mass-univariate and state-of-the-art multivariate pattern analysis to establish which brain regions respond to preferred packages and to what extent neural activation patterns can predict realistic low-involvement consumer choices. More specifically, this was assessed in the context of package-induced binary food choices. Mass-univariate analyses showed that several regions, among which the bilateral striatum, were more strongly activated in response to preferred food packages. Food choices could be predicted with an accuracy of up to 61.2% by activation patterns in brain regions previously found to be involved in healthy food choices (superior frontal gyrus) and visual processing (middle occipital gyrus). In conclusion, this study shows that mass-univariate analysis can detect small package-induced differences in product preference and that MVPA can successfully predict realistic low-involvement consumer choices from functional MRI data. PMID:22848586

Neural signatures of attention: insights from decoding population activity patterns.

PubMed

Sapountzis, Panagiotis; Gregoriou, Georgia G

2018-01-01

Understanding brain function and the computations that individual neurons and neuronal ensembles carry out during cognitive functions is one of the biggest challenges in neuroscientific research. To this end, invasive electrophysiological studies have provided important insights by recording the activity of single neurons in behaving animals. To average out noise, responses are typically averaged across repetitions and across neurons that are usually recorded on different days. However, the brain makes decisions on short time scales based on limited exposure to sensory stimulation by interpreting responses of populations of neurons on a moment to moment basis. Recent studies have employed machine-learning algorithms in attention and other cognitive tasks to decode the information content of distributed activity patterns across neuronal ensembles on a single trial basis. Here, we review results from studies that have used pattern-classification decoding approaches to explore the population representation of cognitive functions. These studies have offered significant insights into population coding mechanisms. Moreover, we discuss how such advances can aid the development of cognitive brain-computer interfaces.

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.

Modality-specific spectral dynamics in response to visual and tactile sequential shape information processing tasks: An MEG study using multivariate pattern classification analysis.

PubMed

Gohel, Bakul; Lee, Peter; Jeong, Yong

2016-08-01

Brain regions that respond to more than one sensory modality are characterized as multisensory regions. Studies on the processing of shape or object information have revealed recruitment of the lateral occipital cortex, posterior parietal cortex, and other regions regardless of input sensory modalities. However, it remains unknown whether such regions show similar (modality-invariant) or different (modality-specific) neural oscillatory dynamics, as recorded using magnetoencephalography (MEG), in response to identical shape information processing tasks delivered to different sensory modalities. Modality-invariant or modality-specific neural oscillatory dynamics indirectly suggest modality-independent or modality-dependent participation of particular brain regions, respectively. Therefore, this study investigated the modality-specificity of neural oscillatory dynamics in the form of spectral power modulation patterns in response to visual and tactile sequential shape-processing tasks that are well-matched in terms of speed and content between the sensory modalities. Task-related changes in spectral power modulation and differences in spectral power modulation between sensory modalities were investigated at source-space (voxel) level, using a multivariate pattern classification (MVPC) approach. Additionally, whole analyses were extended from the voxel level to the independent-component level to take account of signal leakage effects caused by inverse solution. The modality-specific spectral dynamics in multisensory and higher-order brain regions, such as the lateral occipital cortex, posterior parietal cortex, inferior temporal cortex, and other brain regions, showed task-related modulation in response to both sensory modalities. This suggests modality-dependency of such brain regions on the input sensory modality for sequential shape-information processing. Copyright © 2016 Elsevier B.V. All rights reserved.

Early alterations of social brain networks in young children with autism

PubMed Central

Kojovic, Nada; Rihs, Tonia Anahi; Jan, Reem Kais; Franchini, Martina; Plomp, Gijs; Vulliemoz, Serge; Eliez, Stephan; Michel, Christoph Martin; Schaer, Marie

2018-01-01

Social impairments are a hallmark of Autism Spectrum Disorders (ASD), but empirical evidence for early brain network alterations in response to social stimuli is scant in ASD. We recorded the gaze patterns and brain activity of toddlers with ASD and their typically developing peers while they explored dynamic social scenes. Directed functional connectivity analyses based on electrical source imaging revealed frequency specific network atypicalities in the theta and alpha frequency bands, manifesting as alterations in both the driving and the connections from key nodes of the social brain associated with autism. Analyses of brain-behavioural relationships within the ASD group suggested that compensatory mechanisms from dorsomedial frontal, inferior temporal and insular cortical regions were associated with less atypical gaze patterns and lower clinical impairment. Our results provide strong evidence that directed functional connectivity alterations of social brain networks is a core component of atypical brain development at early stages of ASD. PMID:29482718

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.

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.

Acute stress evokes sexually dimorphic, stressor-specific patterns of neural activation across multiple limbic brain regions in adult rats.

PubMed

Sood, Ankit; Chaudhari, Karina; Vaidya, Vidita A

2018-03-01

Stress enhances the risk for psychiatric disorders such as anxiety and depression. Stress responses vary across sex and may underlie the heightened vulnerability to psychopathology in females. Here, we examined the influence of acute immobilization stress (AIS) and a two-day short-term forced swim stress (FS) on neural activation in multiple cortical and subcortical brain regions, implicated as targets of stress and in the regulation of neuroendocrine stress responses, in male and female rats using Fos as a neural activity marker. AIS evoked a sex-dependent pattern of neural activation within the cingulate and infralimbic subdivisions of the medial prefrontal cortex (mPFC), lateral septum (LS), habenula, and hippocampal subfields. The degree of neural activation in the mPFC, LS, and habenula was higher in males. Female rats exhibited reduced Fos positive cell numbers in the dentate gyrus hippocampal subfield, an effect not observed in males. We addressed whether the sexually dimorphic neural activation pattern noted following AIS was also observed with the short-term stress of FS. In the paraventricular nucleus of the hypothalamus and the amygdala, FS similar to AIS resulted in robust increases in neural activation in both sexes. The pattern of neural activation evoked by FS was distinct across sexes, with a heightened neural activation noted in the prelimbic mPFC subdivision and hippocampal subfields in females and differed from the pattern noted with AIS. This indicates that the sex differences in neural activation patterns observed within stress-responsive brain regions are dependent on the nature of stressor experience.

Immune–neural connections: how the immune system’s response to infectious agents influences behavior

PubMed Central

McCusker, Robert H.; Kelley, Keith W.

2013-01-01

Summary Humans and animals use the classical five senses of sight, sound, touch, smell and taste to monitor their environment. The very survival of feral animals depends on these sensory perception systems, which is a central theme in scholarly research on comparative aspects of anatomy and physiology. But how do all of us sense and respond to an infection? We cannot see, hear, feel, smell or taste bacterial and viral pathogens, but humans and animals alike are fully aware of symptoms of sickness that are caused by these microbes. Pain, fatigue, altered sleep pattern, anorexia and fever are common symptoms in both sick animals and humans. Many of these physiological changes represent adaptive responses that are considered to promote animal survival, and this constellation of events results in sickness behavior. Infectious agents display a variety of pathogen-associated molecular patterns (PAMPs) that are recognized by pattern recognition receptors (PRRs). These PRR are expressed on both the surface [e.g. Toll-like receptor (TLR)-4] and in the cytoplasm [e.g. nucleotide-binding oligomerization domain (Nod)-like receptors] of cells of the innate immune system, primarily macrophages and dendritic cells. These cells initiate and propagate an inflammatory response by stimulating the synthesis and release of a variety of cytokines. Once an infection has occurred in the periphery, both cytokines and bacterial toxins deliver this information to the brain using both humoral and neuronal routes of communication. For example, binding of PRR can lead to activation of the afferent vagus nerve, which communicates neuronal signals via the lower brain stem (nucleus tractus solitarius) to higher brain centers such as the hypothalamus and amygdala. Blood-borne cytokines initiate a cytokine response from vascular endothelial cells that form the blood–brain barrier (BBB). Cytokines can also reach the brain directly by leakage through the BBB via circumventricular organs or by being synthesized within the brain, thus forming a mirror image of the cytokine milieu in the periphery. Although all cells within the brain are capable of initiating cytokine secretion, microglia have an early response to incoming neuronal and humoral stimuli. Inhibition of proinflammatory cytokines that are induced following bacterial infection blocks the appearance of sickness behaviors. Collectively, these data are consistent with the notion that the immune system communicates with the brain to regulate behavior in a way that is consistent with animal survival. PMID:23225871

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

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.

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…

Mapping Informative Clusters in a Hierarchial Framework of fMRI Multivariate Analysis

PubMed Central

Xu, Rui; Zhen, Zonglei; Liu, Jia

2010-01-01

Pattern recognition methods have become increasingly popular in fMRI data analysis, which are powerful in discriminating between multi-voxel patterns of brain activities associated with different mental states. However, when they are used in functional brain mapping, the location of discriminative voxels varies significantly, raising difficulties in interpreting the locus of the effect. Here we proposed a hierarchical framework of multivariate approach that maps informative clusters rather than voxels to achieve reliable functional brain mapping without compromising the discriminative power. In particular, we first searched for local homogeneous clusters that consisted of voxels with similar response profiles. Then, a multi-voxel classifier was built for each cluster to extract discriminative information from the multi-voxel patterns. Finally, through multivariate ranking, outputs from the classifiers were served as a multi-cluster pattern to identify informative clusters by examining interactions among clusters. Results from both simulated and real fMRI data demonstrated that this hierarchical approach showed better performance in the robustness of functional brain mapping than traditional voxel-based multivariate methods. In addition, the mapped clusters were highly overlapped for two perceptually equivalent object categories, further confirming the validity of our approach. In short, the hierarchical framework of multivariate approach is suitable for both pattern classification and brain mapping in fMRI studies. PMID:21152081

Functional Brain Activation in Response to a Clinical Vestibular Test Correlates with Balance

PubMed Central

Noohi, Fatemeh; Kinnaird, Catherine; DeDios, Yiri; Kofman, Igor S.; Wood, Scott; Bloomberg, Jacob; Mulavara, Ajitkumar; Seidler, Rachael

2017-01-01

The current study characterizes brain fMRI activation in response to two modes of vestibular stimulation: Skull tap and auditory tone burst. The auditory tone burst has been used in previous studies to elicit either a vestibulo-spinal reflex [saccular-mediated colic Vestibular Evoked Myogenic Potentials (cVEMP)], or an ocular muscle response [utricle-mediated ocular VEMP (oVEMP)]. Research suggests that the skull tap elicits both saccular and utricle-mediated VEMPs, while being faster and less irritating for subjects than the high decibel tones required to elicit VEMPs. However, it is not clear whether the skull tap and auditory tone burst elicit the same pattern of brain activity. Previous imaging studies have documented activity in the anterior and posterior insula, superior temporal gyrus, inferior parietal lobule, inferior frontal gyrus, and the anterior cingulate cortex in response to different modes of vestibular stimulation. Here we hypothesized that pneumatically powered skull taps would elicit a similar pattern of brain activity as shown in previous studies. Our results provide the first evidence of using pneumatically powered skull taps to elicit vestibular activity inside the MRI scanner. A conjunction analysis revealed that skull taps elicit overlapping activation with auditory tone bursts in the canonical vestibular cortical regions. Further, our postural control assessments revealed that greater amplitude of brain activation in response to vestibular stimulation was associated with better balance control for both techniques. Additionally, we found that skull taps elicit more robust vestibular activity compared to auditory tone bursts, with less reported aversive effects, highlighting the utility of this approach for future clinical and basic science research. PMID:28344549

What does brain response to neutral faces tell us about major depression? evidence from machine learning and fMRI.

PubMed

Oliveira, Leticia; Ladouceur, Cecile D; Phillips, Mary L; Brammer, Michael; Mourao-Miranda, Janaina

2013-01-01

A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients. TWO INDEPENDENT DEPRESSED SAMPLES: (1) Nineteen medication-free patients with depression and 19 healthy volunteers and (2) Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral) during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces) using data only from healthy controls (HC). Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier's predictions (predictive probabilities) for emotional and neutral face classification were different for healthy controls and depressed patients. Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1) and happy faces (samples 2) between depressed patients and healthy controls. Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This difference in brain activation might underlie the behavioural misinterpretation of the neutral faces content by the depressed patients.

The way to her heart? Response to romantic cues is dependent on hunger state and dieting history: An fMRI pilot study.

PubMed

Ely, Alice V; Childress, Anna Rose; Jagannathan, Kanchana; Lowe, Michael R

2015-12-01

Normal weight historical dieters (HDs) are prone to future weight gain, and show higher levels of brain activation in reward-related regions after having eaten than nondieters (NDs) in response to food stimuli (Ely, Childress, Jagannathan, & Lowe, 2014), a similar pattern to that seen in obesity. We hypothesized that HDs are differentially sensitive after eating to rewards in general, and thus extended prior findings by comparing the same groups' brain activation when viewing romantic pictures compared to neutral stimuli while being scanned in a blood oxygenation level-dependent (BOLD) fMRI paradigm in a fasted and fed state. Results show that 1) in fed relative to fasted conditions, both HDs and NDs were more responsive in areas related to reward and 2) in HDs, greater fed versus fasted activation extended to areas linked to perception and goal-directed behavior. HDs relative to NDs were more responsive to romantic cues in the superior frontal gyrus when fasted and the middle temporal gyrus when fed. This pattern of response is similar to HDs' activation when viewing highly palatable food cues, and is consistent with research showing overlapping brain-based responses to sex, drugs and food. Copyright © 2015 Elsevier Ltd. All rights reserved.

Idiosyncratic Brain Activation Patterns Are Associated with Poor Social Comprehension in Autism

PubMed Central

Tyszka, J. Michael; Adolphs, Ralph; Kennedy, Daniel P.

2015-01-01

Autism spectrum disorder (ASD) features profound social deficits but neuroimaging studies have failed to find any consistent neural signature. Here we connect these two facts by showing that idiosyncratic patterns of brain activation are associated with social comprehension deficits. Human participants with ASD (N = 17) and controls (N = 20) freely watched a television situation comedy (sitcom) depicting seminaturalistic social interactions (“The Office”, NBC Universal) in the scanner. Intersubject correlations in the pattern of evoked brain activation were reduced in the ASD group—but this effect was driven entirely by five ASD subjects whose idiosyncratic responses were also internally unreliable. The idiosyncrasy of these five ASD subjects was not explained by detailed neuropsychological profile, eye movements, or data quality; however, they were specifically impaired in understanding the social motivations of characters in the sitcom. Brain activation patterns in the remaining ASD subjects were indistinguishable from those of control subjects using multiple multivariate approaches. Our findings link neurofunctional abnormalities evoked by seminaturalistic stimuli with a specific impairment in social comprehension, and highlight the need to conceive of ASD as a heterogeneous classification. PMID:25855192

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.

Personality Is Reflected in the Brain's Intrinsic Functional Architecture

PubMed Central

Adelstein, Jonathan S.; Shehzad, Zarrar; Mennes, Maarten; DeYoung, Colin G.; Zuo, Xi-Nian; Kelly, Clare; Margulies, Daniel S.; Bloomfield, Aaron; Gray, Jeremy R.; Castellanos, F. Xavier; Milham, Michael P.

2011-01-01

Personality describes persistent human behavioral responses to broad classes of environmental stimuli. Investigating how personality traits are reflected in the brain's functional architecture is challenging, in part due to the difficulty of designing appropriate task probes. Resting-state functional connectivity (RSFC) can detect intrinsic activation patterns without relying on any specific task. Here we use RSFC to investigate the neural correlates of the five-factor personality domains. Based on seed regions placed within two cognitive and affective ‘hubs’ in the brain—the anterior cingulate and precuneus—each domain of personality predicted RSFC with a unique pattern of brain regions. These patterns corresponded with functional subdivisions responsible for cognitive and affective processing such as motivation, empathy and future-oriented thinking. Neuroticism and Extraversion, the two most widely studied of the five constructs, predicted connectivity between seed regions and the dorsomedial prefrontal cortex and lateral paralimbic regions, respectively. These areas are associated with emotional regulation, self-evaluation and reward, consistent with the trait qualities. Personality traits were mostly associated with functional connections that were inconsistently present across participants. This suggests that although a fundamental, core functional architecture is preserved across individuals, variable connections outside of that core encompass the inter-individual differences in personality that motivate diverse responses. PMID:22140453

Selective attention to temporal features on nested time scales.

PubMed

Henry, Molly J; Herrmann, Björn; Obleser, Jonas

2015-02-01

Meaningful auditory stimuli such as speech and music often vary simultaneously along multiple time scales. Thus, listeners must selectively attend to, and selectively ignore, separate but intertwined temporal features. The current study aimed to identify and characterize the neural network specifically involved in this feature-selective attention to time. We used a novel paradigm where listeners judged either the duration or modulation rate of auditory stimuli, and in which the stimulation, working memory demands, response requirements, and task difficulty were held constant. A first analysis identified all brain regions where individual brain activation patterns were correlated with individual behavioral performance patterns, which thus supported temporal judgments generically. A second analysis then isolated those brain regions that specifically regulated selective attention to temporal features: Neural responses in a bilateral fronto-parietal network including insular cortex and basal ganglia decreased with degree of change of the attended temporal feature. Critically, response patterns in these regions were inverted when the task required selectively ignoring this feature. The results demonstrate how the neural analysis of complex acoustic stimuli with multiple temporal features depends on a fronto-parietal network that simultaneously regulates the selective gain for attended and ignored temporal features. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sex differences in brain response to anticipated and experienced visceral pain in healthy subjects.

PubMed

Kano, Michiko; Farmer, Adam D; Aziz, Qasim; Giampietro, Vincent P; Brammer, Michael J; Williams, Steven C R; Fukudo, Shin; Coen, Steven J

2013-04-15

Women demonstrate higher pain sensitivity and prevalence of chronic visceral pain conditions such as functional gastrointestinal disorders than men. The role of sex differences in the brain processing of visceral pain is still unclear. In 16 male and 16 female healthy subjects we compared personality, anxiety levels, skin conductance response (SCR), and brain processing using functional MRI during anticipation and pain induced by esophageal distension at pain toleration level. There was no significant difference in personality scores, anxiety levels, SCR, and subjective ratings of pain between sexes. In group analysis, both men and women demonstrated a similar pattern of brain activation and deactivation during anticipation and pain consistent with previous reports. However, during anticipation women showed significantly greater activation in the cuneus, precuneus, and supplementary motor area (SMA) and stronger deactivation in the right amygdala and left parahippocampal gyrus, whereas men demonstrated greater activation in the cerebellum. During pain, women demonstrated greater activation in the midcingulate cortex, anterior insula, premotor cortex, and cerebellum and stronger deactivation in the caudate, whereas men showed increased activity in the SMA. The pattern of brain activity suggests that, during anticipation, women may demonstrate stronger limbic inhibition, which is considered to be a cognitive modulation strategy for impending painful stimulation. During pain, women significantly activate brain areas associated with the affective and motivation components of pain. These responses may underlie the sex differences that exist in pain conditions, whereby women may attribute more emotional importance to painful stimuli compared with men.

Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair.

PubMed

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

2014-04-01

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 dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke. Published by Elsevier Ltd.

Repeated Ferret Odor Exposure Induces Different Temporal Patterns of Same-Stressor Habituation and Novel-Stressor Sensitization in Both Hypothalamic-Pituitary-Adrenal Axis Activity and Forebrain c-fos Expression in the Rat

PubMed Central

Weinberg, Marc S.; Bhatt, Aadra P.; Girotti, Milena; Masini, Cher V.; Day, Heidi E. W.; Campeau, Serge; Spencer, Robert L.

2009-01-01

Repeated exposure to a moderately intense stressor typically produces attenuation of the hypothalamic-pituitary-adrenal (HPA) axis response (habituation) on re-presentation of the same stressor; however, if a novel stressor is presented to the same animals, the HPA axis response may be augmented (sensitization). The extent to which this adaptation is also evident within neural activity patterns is unknown. This study tested whether repeated ferret odor (FO) exposure, a moderately intense psychological stressor for rats, leads to both same-stressor habituation and novel-stressor sensitization of the HPA axis response and neuronal activity as determined by immediate early gene induction (c-fos mRNA). Rats were presented with FO in their home cages for 30 min a day for up to 2 wk and subsequently challenged with FO or restraint. Rats displayed HPA axis activity habituation and widespread habituation of c-fos mRNA expression (in situ hybridization) throughout the brain in as few as three repeated presentations of FO. However, repeated FO exposure led to a more gradual development of sensitized HPA-axis and c-fos mRNA responses to restraint that were not fully evident until after 14 d of prior FO exposure. The sensitized response was evident in many of the same brain regions that displayed habituation, including primary sensory cortices and the prefrontal cortex. The shared spatial expression but distinct temporal development of habituation and sensitization neural response patterns suggests two independent processes with opposing influences across overlapping brain systems. PMID:18845631

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.

Whole person-evoked fMRI activity patterns in human fusiform gyrus are accurately modeled by a linear combination of face- and body-evoked activity patterns

PubMed Central

Kaiser, Daniel; Strnad, Lukas; Seidl, Katharina N.; Kastner, Sabine

2013-01-01

Visual cues from the face and the body provide information about another's identity, emotional state, and intentions. Previous neuroimaging studies that investigated neural responses to (bodiless) faces and (headless) bodies have reported overlapping face- and body-selective brain regions in right fusiform gyrus (FG). In daily life, however, faces and bodies are typically perceived together and are effortlessly integrated into the percept of a whole person, raising the possibility that neural responses to whole persons are qualitatively different than responses to isolated faces and bodies. The present study used fMRI to examine how FG activity in response to a whole person relates to activity in response to the same face and body but presented in isolation. Using multivoxel pattern analysis, we modeled person-evoked response patterns in right FG through a linear combination of face- and body-evoked response patterns. We found that these synthetic patterns were able to accurately approximate the response patterns to whole persons, with face and body patterns each adding unique information to the response patterns evoked by whole person stimuli. These results suggest that whole person responses in FG primarily arise from the coactivation of independent face- and body-selective neural populations. PMID:24108794

Collaborative Brain-Computer Interface for Aiding Decision-Making

PubMed Central

Poli, Riccardo; Valeriani, Davide; Cinel, Caterina

2014-01-01

We look at the possibility of integrating the percepts from multiple non-communicating observers as a means of achieving better joint perception and better group decisions. Our approach involves the combination of a brain-computer interface with human behavioural responses. To test ideas in controlled conditions, we asked observers to perform a simple matching task involving the rapid sequential presentation of pairs of visual patterns and the subsequent decision as whether the two patterns in a pair were the same or different. We recorded the response times of observers as well as a neural feature which predicts incorrect decisions and, thus, indirectly indicates the confidence of the decisions made by the observers. We then built a composite neuro-behavioural feature which optimally combines the two measures. For group decisions, we uses a majority rule and three rules which weigh the decisions of each observer based on response times and our neural and neuro-behavioural features. Results indicate that the integration of behavioural responses and neural features can significantly improve accuracy when compared with the majority rule. An analysis of event-related potentials indicates that substantial differences are present in the proximity of the response for correct and incorrect trials, further corroborating the idea of using hybrids of brain-computer interfaces and traditional strategies for improving decision making. PMID:25072739

Hypoxia Stress Modifies Na+/K+-ATPase, H+/K+-ATPase, Na+/NH4+-ATPase, and nkaα1 Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish

PubMed Central

Peter, MC Subhash; Simi, Satheesan

2017-01-01

Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA) expression of α1-subunit isoforms of Na+/K+-ATPase (NKA) in the brain segments, namely, prosencephalon (PC), mesencephalon (MC), and metencephalon (MeC) in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water) or challenged with zymosan treatment (25-200 ng g−1 for 24 hours) or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H+/K+-ATPase (HKA), and Na+/NH4+-ATPase (NNA) in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a, nkaα1b, and nkaα1c, in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na+, K+, H+, and NH4+ ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform regulation. PMID:29238219

Hypoxia Stress Modifies Na+/K+-ATPase, H+/K+-ATPase, [Formula: see text], and nkaα1 Isoform Expression in the Brain of Immune-Challenged Air-Breathing Fish.

PubMed

Peter, Mc Subhash; Simi, Satheesan

2017-01-01

Fishes are equipped to sense stressful stimuli and are able to respond to environmental stressor such as hypoxia with varying pattern of stress response. The functional attributes of brain to hypoxia stress in relation to ion transport and its interaction during immune challenge have not yet delineated in fish. We, therefore, explored the pattern of ion transporter functions and messenger RNA (mRNA) expression of α1-subunit isoforms of Na + /K + -ATPase (NKA) in the brain segments, namely, prosencephalon (PC), mesencephalon (MC), and metencephalon (MeC) in an obligate air-breathing fish exposed either to hypoxia stress (30 minutes forced immersion in water) or challenged with zymosan treatment (25-200 ng g -1 for 24 hours) or both. Zymosan that produced nonspecific immune responses evoked differential regulation of NKA, H + /K + -ATPase (HKA), and [Formula: see text] (NNA) in the varied brain segments. On the contrary, hypoxia stress that demanded activation of NKA in PC and MeC showed a reversed NKA activity pattern in MeC of immune-challenged fish. A compromised HKA and NNA regulation during hypoxia stress was found in immune-challenged fish, indicating the role of these brain ion transporters to hypoxia stress and immune challenges. The differential mRNA expression of α1-subunit isoforms of NKA, nkaα1a , nkaα1b , and nkaα1c , in hypoxia-stressed brain showed a shift in its expression pattern during hypoxia stress-immune interaction in PC and MC. Evidence is thus presented for the first time that ion transporters such as HKA and NNA along with NKA act as functional brain markers which respond differentially to both hypoxia stress and immune challenges. Taken together, the data further provide evidence for a differential Na + , K + , H + , and [Formula: see text] ion signaling that exists in brain neuronal clusters during hypoxia stress-immune interaction as a result of modified regulations of NKA, HKA, and NNA transporter functions and nkaα1 isoform regulation.

4-dimensional functional profiling in the convulsant-treated larval zebrafish brain.

PubMed

Winter, Matthew J; Windell, Dylan; Metz, Jeremy; Matthews, Peter; Pinion, Joe; Brown, Jonathan T; Hetheridge, Malcolm J; Ball, Jonathan S; Owen, Stewart F; Redfern, Will S; Moger, Julian; Randall, Andrew D; Tyler, Charles R

2017-07-26

Functional neuroimaging, using genetically-encoded Ca 2+ sensors in larval zebrafish, offers a powerful combination of high spatiotemporal resolution and higher vertebrate relevance for quantitative neuropharmacological profiling. Here we use zebrafish larvae with pan-neuronal expression of GCaMP6s, combined with light sheet microscopy and a novel image processing pipeline, for the 4D profiling of chemoconvulsant action in multiple brain regions. In untreated larvae, regions associated with autonomic functionality, sensory processing and stress-responsiveness, consistently exhibited elevated spontaneous activity. The application of drugs targeting different convulsant mechanisms (4-Aminopyridine, Pentylenetetrazole, Pilocarpine and Strychnine) resulted in distinct spatiotemporal patterns of activity. These activity patterns showed some interesting parallels with what is known of the distribution of their respective molecular targets, but crucially also revealed system-wide neural circuit responses to stimulation or suppression. Drug concentration-response curves of neural activity were identified in a number of anatomically-defined zebrafish brain regions, and in vivo larval electrophysiology, also conducted in 4dpf larvae, provided additional measures of neural activity. Our quantification of network-wide chemoconvulsant drug activity in the whole zebrafish brain illustrates the power of this approach for neuropharmacological profiling in applications ranging from accelerating studies of drug safety and efficacy, to identifying pharmacologically-altered networks in zebrafish models of human neurological disorders.

A neuroanatomically grounded Hebbian-learning model of attention–language interactions in the human brain

PubMed Central

Garagnani, Max; Wennekers, Thomas; Pulvermüller, Friedemann

2008-01-01

Meaningful familiar stimuli and senseless unknown materials lead to different patterns of brain activation. A late major neurophysiological response indexing ‘sense’ is the negative component of event-related potential peaking at around 400 ms (N400), an event-related potential that emerges in attention-demanding tasks and is larger for senseless materials (e.g. meaningless pseudowords) than for matched meaningful stimuli (words). However, the mismatch negativity (latency 100–250 ms), an early automatic brain response elicited under distraction, is larger to words than to pseudowords, thus exhibiting the opposite pattern to that seen for the N400. So far, no theoretical account has been able to reconcile and explain these findings by means of a single, mechanistic neural model. We implemented a neuroanatomically grounded neural network model of the left perisylvian language cortex and simulated: (i) brain processes of early language acquisition and (ii) cortical responses to familiar word and senseless pseudoword stimuli. We found that variation of the area-specific inhibition (the model correlate of attention) modulated the simulated brain response to words and pseudowords, producing either an N400- or a mismatch negativity-like response depending on the amount of inhibition (i.e. available attentional resources). Our model: (i) provides a unifying explanatory account, at cortical level, of experimental observations that, so far, had not been given a coherent interpretation within a single framework; (ii) demonstrates the viability of purely Hebbian, associative learning in a multilayered neural network architecture; and (iii) makes clear predictions on the effects of attention on latency and magnitude of event-related potentials to lexical items. Such predictions have been confirmed by recent experimental evidence. PMID:18215243

Treatment patterns and outcomes in BRAF V600E-mutant melanoma patients with brain metastases receiving vemurafenib in the real-world setting.

PubMed

Gibney, Geoffrey T; Gauthier, Geneviève; Ayas, Charles; Galebach, Philip; Wu, Eric Q; Abhyankar, Sarang; Reyes, Carolina; Guérin, Annie; Yim, Yeun Mi

2015-08-01

Brain metastases are a common and serious complication among patients with metastatic melanoma. The selective BRAF inhibitor vemurafenib has demonstrated clinical efficacy in patients with BRAF V600E-mutant melanoma brain metastases (MBM). We examined the real-world application and clinical outcomes of vemurafenib in this patient population. Demographic, treatment patterns, response, and survival data were collected from medical charts. Clinical data on 283 patients with active BRAF V600E-mutant MBM treated with vemurafenib were provided by 70 US oncologists. Mean age was 57.2 years, 60.8% were male, 67.5% had ECOG performance status of 0-1, and 43.1% used corticosteroids at vemurafenib initiation. Median follow-up was 5.7 months. Following vemurafenib initiation, 48.1% of patients experienced intracranial response and 45.6% experienced extracranial response. The Kaplan-Meier estimate for overall survival was 59% at 12 months. Multivariate analyses showed associations between intracranial response and both corticosteroid use and vemurafenib as initial therapy after MBM diagnosis. Larger size (5-10 mm vs. < 5 mm) and number of brain metastases (≥ 5 vs. < 2) and progressive extracranial disease at treatment initiation were associated with decreased intracranial response and increased risk of disease progression. Multiple extracranial sites (2 vs. < 2) and the absence of local treatments were also associated with increased risk of progression. Increased risk of death was associated with ≥ 2 extracranial disease sites, progressive extracranial disease, and ≥ 5 brain metastases. Subgroups of MBM patients may derive more benefit with vemurafenib, warranting prospective investigation. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Involvement of neuronal IL-1β in acquired brain lesions in a rat model of neonatal encephalopathy.

PubMed

Savard, Alexandre; Lavoie, Karine; Brochu, Marie-Elsa; Grbic, Djordje; Lepage, Martin; Gris, Denis; Sebire, Guillaume

2013-09-05

Infection-inflammation combined with hypoxia-ischemia (HI) is the most prevalent pathological scenario involved in perinatal brain damage leading to life-long neurological disabilities. Following lipopolysaccharide (LPS) and/or HI aggression, different patterns of inflammatory responses have been uncovered according to the brain differentiation stage. In fact, LPS pre-exposure has been reported to aggravate HI brain lesions in post-natal day 1 (P1) and P7 rat models that are respectively equivalent - in terms of brain development - to early and late human preterm newborns. However, little is known about the innate immune response in LPS plus HI-induced lesions of the full-term newborn forebrain and the associated neuropathological and neurobehavioral outcomes. An original preclinical rat model has been previously documented for the innate neuroimmune response at different post-natal ages. It was used in the present study to investigate the neuroinflammatory mechanisms that underline neurological impairments after pathogen-induced inflammation and HI in term newborns. LPS and HI exerted a synergistic detrimental effect on rat brain. Their effect led to a peculiar pattern of parasagittal cortical-subcortical infarcts mimicking those in the human full-term newborn with subsequent severe neurodevelopmental impairments. An increased IL-1β response in neocortical and basal gray neurons was demonstrated at 4 h after LPS + HI-exposure and preceded other neuroinflammatory responses such as microglial and astroglial cell activation. Neurological deficits were observed during the acute phase of injury followed by a recovery, then by a delayed onset of profound motor behavior impairment, reminiscent of the delayed clinical onset of motor system impairments observed in humans. Interleukin-1 receptor antagonist (IL-1ra) reduced the extent of brain lesions confirming the involvement of IL-1β response in their pathophysiology. In rat pups at a neurodevelopmental age corresponding to full-term human newborns, a systemic pre-exposure to a pathogen component amplified HI-induced mortality and morbidities that are relevant to human pathology. Neuronal cells were the first cells to produce IL-1β in LPS + HI-exposed full-term brains. Such IL-1β production might be responsible for neuronal self-injuries via well-described neurotoxic mechanisms such as IL-1β-induced nitric oxide production, or IL-1β-dependent exacerbation of excitotoxic damage.

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

Behavioral and brain pattern differences between acting and observing in an auditory task

PubMed Central

Karanasiou, Irene S; Papageorgiou, Charalabos; Tsianaka, Eleni I; Matsopoulos, George K; Ventouras, Errikos M; Uzunoglu, Nikolaos K

2009-01-01

Background Recent research has shown that errors seem to influence the patterns of brain activity. Additionally current notions support the idea that similar brain mechanisms are activated during acting and observing. The aim of the present study was to examine the patterns of brain activity of actors and observers elicited upon receiving feedback information of the actor's response. Methods The task used in the present research was an auditory identification task that included both acting and observing settings, ensuring concurrent ERP measurements of both participants. The performance of the participants was investigated in conditions of varying complexity. ERP data were analyzed with regards to the conditions of acting and observing in conjunction to correct and erroneous responses. Results The obtained results showed that the complexity induced by cue dissimilarity between trials was a demodulating factor leading to poorer performance. The electrophysiological results suggest that feedback information results in different intensities of the ERP patterns of observers and actors depending on whether the actor had made an error or not. The LORETA source localization method yielded significantly larger electrical activity in the supplementary motor area (Brodmann area 6), the posterior cingulate gyrus (Brodmann area 31/23) and the parietal lobe (Precuneus/Brodmann area 7/5). Conclusion These findings suggest that feedback information has a different effect on the intensities of the ERP patterns of actors and observers depending on whether the actor committed an error. Certain neural systems, including medial frontal area, posterior cingulate gyrus and precuneus may mediate these modulating effects. Further research is needed to elucidate in more detail the neuroanatomical and neuropsychological substrates of these systems. PMID:19154586

Evolution of brain region volumes during artificial selection for relative brain size.

PubMed

Kotrschal, Alexander; Zeng, Hong-Li; van der Bijl, Wouter; Öhman-Mägi, Caroline; Kotrschal, Kurt; Pelckmans, Kristiaan; Kolm, Niclas

2017-12-01

The vertebrate brain shows an extremely conserved layout across taxa. Still, the relative sizes of separate brain regions vary markedly between species. One interesting pattern is that larger brains seem associated with increased relative sizes only of certain brain regions, for instance telencephalon and cerebellum. Till now, the evolutionary association between separate brain regions and overall brain size is based on comparative evidence and remains experimentally untested. Here, we test the evolutionary response of brain regions to directional selection on brain size in guppies (Poecilia reticulata) selected for large and small relative brain size. In these animals, artificial selection led to a fast response in relative brain size, while body size remained unchanged. We use microcomputer tomography to investigate how the volumes of 11 main brain regions respond to selection for larger versus smaller brains. We found no differences in relative brain region volumes between large- and small-brained animals and only minor sex-specific variation. Also, selection did not change allometric scaling between brain and brain region sizes. Our results suggest that brain regions respond similarly to strong directional selection on relative brain size, which indicates that brain anatomy variation in contemporary species most likely stem from direct selection on key regions. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Neural Activity Patterns in the Human Brain Reflect Tactile Stickiness Perception.

PubMed

Kim, Junsuk; Yeon, Jiwon; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

2017-01-01

Our previous human fMRI study found brain activations correlated with tactile stickiness perception using the uni-variate general linear model (GLM) (Yeon et al., 2017). Here, we conducted an in-depth investigation on neural correlates of sticky sensations by employing a multivoxel pattern analysis (MVPA) on the same dataset. In particular, we statistically compared multi-variate neural activities in response to the three groups of sticky stimuli: A supra-threshold group including a set of sticky stimuli that evoked vivid sticky perception; an infra-threshold group including another set of sticky stimuli that barely evoked sticky perception; and a sham group including acrylic stimuli with no physically sticky property. Searchlight MVPAs were performed to search for local activity patterns carrying neural information of stickiness perception. Similar to the uni-variate GLM results, significant multi-variate neural activity patterns were identified in postcentral gyrus, subcortical (basal ganglia and thalamus), and insula areas (insula and adjacent areas). Moreover, MVPAs revealed that activity patterns in posterior parietal cortex discriminated the perceptual intensities of stickiness, which was not present in the uni-variate analysis. Next, we applied a principal component analysis (PCA) to the voxel response patterns within identified clusters so as to find low-dimensional neural representations of stickiness intensities. Follow-up clustering analyses clearly showed separate neural grouping configurations between the Supra- and Infra-threshold groups. Interestingly, this neural categorization was in line with the perceptual grouping pattern obtained from the psychophysical data. Our findings thus suggest that different stickiness intensities would elicit distinct neural activity patterns in the human brain and may provide a neural basis for the perception and categorization of tactile stickiness.

Neural Activity Patterns in the Human Brain Reflect Tactile Stickiness Perception

PubMed Central

Kim, Junsuk; Yeon, Jiwon; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

2017-01-01

Our previous human fMRI study found brain activations correlated with tactile stickiness perception using the uni-variate general linear model (GLM) (Yeon et al., 2017). Here, we conducted an in-depth investigation on neural correlates of sticky sensations by employing a multivoxel pattern analysis (MVPA) on the same dataset. In particular, we statistically compared multi-variate neural activities in response to the three groups of sticky stimuli: A supra-threshold group including a set of sticky stimuli that evoked vivid sticky perception; an infra-threshold group including another set of sticky stimuli that barely evoked sticky perception; and a sham group including acrylic stimuli with no physically sticky property. Searchlight MVPAs were performed to search for local activity patterns carrying neural information of stickiness perception. Similar to the uni-variate GLM results, significant multi-variate neural activity patterns were identified in postcentral gyrus, subcortical (basal ganglia and thalamus), and insula areas (insula and adjacent areas). Moreover, MVPAs revealed that activity patterns in posterior parietal cortex discriminated the perceptual intensities of stickiness, which was not present in the uni-variate analysis. Next, we applied a principal component analysis (PCA) to the voxel response patterns within identified clusters so as to find low-dimensional neural representations of stickiness intensities. Follow-up clustering analyses clearly showed separate neural grouping configurations between the Supra- and Infra-threshold groups. Interestingly, this neural categorization was in line with the perceptual grouping pattern obtained from the psychophysical data. Our findings thus suggest that different stickiness intensities would elicit distinct neural activity patterns in the human brain and may provide a neural basis for the perception and categorization of tactile stickiness. PMID:28936171

Caffeine restores regional brain activation in acute hypoglycaemia in healthy volunteers.

PubMed

Rosenthal, M J; Smith, D; Yaguez, L; Giampietro, V; Kerr, D; Bullmore, E; Brammer, M; Williams, S C R; Amiel, S A

2007-07-01

Caffeine enhances counterregulatory responses to acute hypoglycaemia. Our aim was to explore its effects on cortical function, which are not known at present. Regional brain activation during performance of the four-choice reaction time (4CRT) at different levels of complexity was measured using functional magnetic resonance imaging (fMRI) at euglycaemia (5 mmol/l) and hypoglycaemia (2.6 mmol/l) in the presence and absence of caffeine in six healthy right-handed men. During hypoglycaemia, caffeine enhanced adrenaline responses to hypoglycaemia (2.5 +/- 0.7 nmol/l to 4.0 +/- 1.0 nmol/l, P = 0.01) and restored the brain activation response to the non-cued 4CRT, the linear increases in regional brain activation associated with increased task complexity and the ability to respond to a cue that were lost in hypoglycaemia alone. Caffeine can sustain regional brain activation patterns lost in acute hypoglycaemia, with some restoration of cortical function and enhanced adrenaline responsiveness. A methodology has been established that may help in the development of therapies to protect against severe hypoglycaemia in insulin therapy for patients with diabetes and problematic hypoglycaemia.

fMRI activation patterns in an analytic reasoning task: consistency with EEG source localization

NASA Astrophysics Data System (ADS)

Li, Bian; Vasanta, Kalyana C.; O'Boyle, Michael; Baker, Mary C.; Nutter, Brian; Mitra, Sunanda

2010-03-01

Functional magnetic resonance imaging (fMRI) is used to model brain activation patterns associated with various perceptual and cognitive processes as reflected by the hemodynamic (BOLD) response. While many sensory and motor tasks are associated with relatively simple activation patterns in localized regions, higher-order cognitive tasks may produce activity in many different brain areas involving complex neural circuitry. We applied a recently proposed probabilistic independent component analysis technique (PICA) to determine the true dimensionality of the fMRI data and used EEG localization to identify the common activated patterns (mapped as Brodmann areas) associated with a complex cognitive task like analytic reasoning. Our preliminary study suggests that a hybrid GLM/PICA analysis may reveal additional regions of activation (beyond simple GLM) that are consistent with electroencephalography (EEG) source localization patterns.

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

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

The heart-break of social rejection versus the brain wave of social acceptance

PubMed Central

van der Molen, Maurits W.; Sahibdin, Priya P.; Franken, Ingmar H. A.

2014-01-01

The effect of social rejection on cardiac and brain responses was examined in a study in which participants had to decide on the basis of pictures of virtual peers whether these peers would like them or not. Physiological and behavioral responses to expected and unexpected acceptance and rejection were compared. It was found that participants expected that about 50% of the virtual judges gave them a positive judgment. Cardiac deceleration was strongest for unexpected social rejection. In contrast, the brain response was strongest to expected acceptance and was characterized by a positive deflection peaking around 325 ms following stimulus onset and the observed difference was maximal at fronto-central positions. The cardiac and electro-cortical responses were not related. It is hypothesized that these differential response patterns might be related to earlier described differential involvement of the dorsal and ventral portion of the anterior cingulate cortex. PMID:23887821

Where the Brain Appreciates the Final State of an Event: The Neural Correlates of Telicity

ERIC Educational Resources Information Center

Romagno, Domenica; Rota, Giuseppina; Ricciardi, Emiliano; Pietrini, Pietro

2012-01-01

In this study we investigated whether the human brain distinguishes between telic events that necessarily entail a specified endpoint (e.g., "reaching"), and atelic events with no delimitation or final state (e.g., "chasing"). We used functional magnetic resonance imaging to explore the patterns of neural response associated with verbs denoting…

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

Methylphenidate Modulates Functional Network Connectivity to Enhance Attention

PubMed Central

Zhang, Sheng; Hsu, Wei-Ting; Scheinost, Dustin; Finn, Emily S.; Shen, Xilin; Constable, R. Todd; Li, Chiang-Shan R.; Chun, Marvin M.

2016-01-01

Recent work has demonstrated that human whole-brain functional connectivity patterns measured with fMRI contain information about cognitive abilities, including sustained attention. To derive behavioral predictions from connectivity patterns, our group developed a connectome-based predictive modeling (CPM) approach (Finn et al., 2015; Rosenberg et al., 2016). Previously using CPM, we defined a high-attention network, comprising connections positively correlated with performance on a sustained attention task, and a low-attention network, comprising connections negatively correlated with performance. Validating the networks as generalizable biomarkers of attention, models based on network strength at rest predicted attention-deficit/hyperactivity disorder (ADHD) symptoms in an independent group of individuals (Rosenberg et al., 2016). To investigate whether these networks play a causal role in attention, here we examined their strength in healthy adults given methylphenidate (Ritalin), a common ADHD treatment, compared with unmedicated controls. As predicted, individuals given methylphenidate showed patterns of connectivity associated with better sustained attention: higher high-attention and lower low-attention network strength than controls. There was significant overlap between the high-attention network and a network with greater strength in the methylphenidate group, and between the low-attention network and a network with greater strength in the control group. Network strength also predicted behavior on a stop-signal task, such that participants with higher go response rates showed higher high-attention and lower low-attention network strength. These results suggest that methylphenidate acts by modulating functional brain networks related to sustained attention, and that changing whole-brain connectivity patterns may help improve attention. SIGNIFICANCE STATEMENT Recent work identified a promising neuromarker of sustained attention based on whole-brain functional connectivity networks. To investigate the causal role of these networks in attention, we examined their response to a dose of methylphenidate, a common and effective treatment for attention-deficit/hyperactivity disorder, in healthy adults. As predicted, individuals on methylphenidate showed connectivity signatures of better sustained attention: higher high-attention and lower low-attention network strength than controls. These results suggest that methylphenidate acts by modulating strength in functional brain networks related to attention, and that changing whole-brain connectivity patterns may improve attention. PMID:27629707

Methylphenidate Modulates Functional Network Connectivity to Enhance Attention.

PubMed

Rosenberg, Monica D; Zhang, Sheng; Hsu, Wei-Ting; Scheinost, Dustin; Finn, Emily S; Shen, Xilin; Constable, R Todd; Li, Chiang-Shan R; Chun, Marvin M

2016-09-14

Recent work has demonstrated that human whole-brain functional connectivity patterns measured with fMRI contain information about cognitive abilities, including sustained attention. To derive behavioral predictions from connectivity patterns, our group developed a connectome-based predictive modeling (CPM) approach (Finn et al., 2015; Rosenberg et al., 2016). Previously using CPM, we defined a high-attention network, comprising connections positively correlated with performance on a sustained attention task, and a low-attention network, comprising connections negatively correlated with performance. Validating the networks as generalizable biomarkers of attention, models based on network strength at rest predicted attention-deficit/hyperactivity disorder (ADHD) symptoms in an independent group of individuals (Rosenberg et al., 2016). To investigate whether these networks play a causal role in attention, here we examined their strength in healthy adults given methylphenidate (Ritalin), a common ADHD treatment, compared with unmedicated controls. As predicted, individuals given methylphenidate showed patterns of connectivity associated with better sustained attention: higher high-attention and lower low-attention network strength than controls. There was significant overlap between the high-attention network and a network with greater strength in the methylphenidate group, and between the low-attention network and a network with greater strength in the control group. Network strength also predicted behavior on a stop-signal task, such that participants with higher go response rates showed higher high-attention and lower low-attention network strength. These results suggest that methylphenidate acts by modulating functional brain networks related to sustained attention, and that changing whole-brain connectivity patterns may help improve attention. Recent work identified a promising neuromarker of sustained attention based on whole-brain functional connectivity networks. To investigate the causal role of these networks in attention, we examined their response to a dose of methylphenidate, a common and effective treatment for attention-deficit/hyperactivity disorder, in healthy adults. As predicted, individuals on methylphenidate showed connectivity signatures of better sustained attention: higher high-attention and lower low-attention network strength than controls. These results suggest that methylphenidate acts by modulating strength in functional brain networks related to attention, and that changing whole-brain connectivity patterns may improve attention. Copyright © 2016 the authors 0270-6474/16/369547-11$15.00/0.

Decoding Dynamic Brain Patterns from Evoked Responses: A Tutorial on Multivariate Pattern Analysis Applied to Time Series Neuroimaging Data.

PubMed

Grootswagers, Tijl; Wardle, Susan G; Carlson, Thomas A

2017-04-01

Multivariate pattern analysis (MVPA) or brain decoding methods have become standard practice in analyzing fMRI data. Although decoding methods have been extensively applied in brain-computer interfaces, these methods have only recently been applied to time series neuroimaging data such as MEG and EEG to address experimental questions in cognitive neuroscience. In a tutorial style review, we describe a broad set of options to inform future time series decoding studies from a cognitive neuroscience perspective. Using example MEG data, we illustrate the effects that different options in the decoding analysis pipeline can have on experimental results where the aim is to "decode" different perceptual stimuli or cognitive states over time from dynamic brain activation patterns. We show that decisions made at both preprocessing (e.g., dimensionality reduction, subsampling, trial averaging) and decoding (e.g., classifier selection, cross-validation design) stages of the analysis can significantly affect the results. In addition to standard decoding, we describe extensions to MVPA for time-varying neuroimaging data including representational similarity analysis, temporal generalization, and the interpretation of classifier weight maps. Finally, we outline important caveats in the design and interpretation of time series decoding experiments.

Neural feedback for instantaneous spatiotemporal modulation of afferent pathways in bi-directional brain-machine interfaces.

PubMed

Liu, Jianbo; Khalil, Hassan K; Oweiss, Karim G

2011-10-01

In bi-directional brain-machine interfaces (BMIs), precisely controlling the delivery of microstimulation, both in space and in time, is critical to continuously modulate the neural activity patterns that carry information about the state of the brain-actuated device to sensory areas in the brain. In this paper, we investigate the use of neural feedback to control the spatiotemporal firing patterns of neural ensembles in a model of the thalamocortical pathway. Control of pyramidal (PY) cells in the primary somatosensory cortex (S1) is achieved based on microstimulation of thalamic relay cells through multiple-input multiple-output (MIMO) feedback controllers. This closed loop feedback control mechanism is achieved by simultaneously varying the stimulation parameters across multiple stimulation electrodes in the thalamic circuit based on continuous monitoring of the difference between reference patterns and the evoked responses of the cortical PY cells. We demonstrate that it is feasible to achieve a desired level of performance by controlling the firing activity pattern of a few "key" neural elements in the network. Our results suggest that neural feedback could be an effective method to facilitate the delivery of information to the cortex to substitute lost sensory inputs in cortically controlled BMIs.

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

Medication Overuse Headache: Pathophysiological Insights from Structural and Functional Brain MRI Research.

PubMed

Schwedt, Todd J; Chong, Catherine D

2017-07-01

Research imaging of brain structure and function has helped to elucidate the pathophysiology of medication overuse headache (MOH). This is a narrative review of imaging research studies that have investigated brain structural and functional alterations associated with MOH. Studies included in this review have investigated abnormal structure and function of pain processing regions in people with MOH, functional patterns that might predispose individuals to development of MOH, similarity of brain functional patterns in patients with MOH to those found in people with addiction, brain structure that could predict headache improvement following discontinuation of the overused medication, and changes in brain structure and function after discontinuation of medication overuse. MOH is associated with atypical structure and function of brain regions responsible for pain processing as well as brain regions that are commonly implicated in addiction. Several studies have shown "normalization" of structure and function in pain processing regions following discontinuation of the overused medication and resolution of MOH. However, some of the abnormalities in regions also implicated in addiction tend to persist following discontinuation of the overused medication, suggesting that they are a brain trait that predisposes certain individuals to medication overuse and MOH. © 2017 American Headache Society.

Cluster analysis and subgrouping to investigate inter-individual variability to non-invasive brain stimulation: a systematic review.

PubMed

Pellegrini, Michael; Zoghi, Maryam; Jaberzadeh, Shapour

2018-01-12

Cluster analysis and other subgrouping techniques have risen in popularity in recent years in non-invasive brain stimulation research in the attempt to investigate the issue of inter-individual variability - the issue of why some individuals respond, as traditionally expected, to non-invasive brain stimulation protocols and others do not. Cluster analysis and subgrouping techniques have been used to categorise individuals, based on their response patterns, as responder or non-responders. There is, however, a lack of consensus and consistency on the most appropriate technique to use. This systematic review aimed to provide a systematic summary of the cluster analysis and subgrouping techniques used to date and suggest recommendations moving forward. Twenty studies were included that utilised subgrouping techniques, while seven of these additionally utilised cluster analysis techniques. The results of this systematic review appear to indicate that statistical cluster analysis techniques are effective in identifying subgroups of individuals based on response patterns to non-invasive brain stimulation. This systematic review also reports a lack of consensus amongst researchers on the most effective subgrouping technique and the criteria used to determine whether an individual is categorised as a responder or a non-responder. This systematic review provides a step-by-step guide to carrying out statistical cluster analyses and subgrouping techniques to provide a framework for analysis when developing further insights into the contributing factors of inter-individual variability in response to non-invasive brain stimulation.

Characterization of basal gene expression trends over a diurnal cycle in Xiphophorus maculatus skin, brain and liver.

PubMed

Lu, Yuan; Reyes, Jose; Walter, Sean; Gonzalez, Trevor; Medrano, Geraldo; Boswell, Mikki; Boswell, William; Savage, Markita; Walter, Ronald

2018-06-01

Evolutionarily conserved diurnal circadian mechanisms maintain oscillating patterns of gene expression based on the day-night cycle. Xiphophorus fish have been used to evaluate transcriptional responses after exposure to various light sources and it was determined that each source incites distinct genetic responses in skin tissue. However, basal expression levels of genes that show oscillating expression patterns in day-night cycle, may affect the outcomes of such experiments, since basal gene expression levels at each point in the circadian path may influence the profile of identified light responsive genes. Lack of knowledge regarding diurnal fluctuations in basal gene expression patterns may confound the understanding of genetic responses to external stimuli (e.g., light) since the dynamic nature of gene expression implies animals subjected to stimuli at different times may be at very different stages within the continuum of genetic homeostasis. We assessed basal gene expression changes over a 24-hour period in 200 select Xiphophorus gene targets known to transcriptionally respond to various types of light exposure. We identified 22 genes in skin, 36 genes in brain and 28 genes in liver that exhibit basal oscillation of expression patterns. These genes, including known circadian regulators, produced the expected expression patterns over a 24-hour cycle when compared to circadian regulatory genes identified in other species, especially human and other vertebrate animal models. Our results suggest the regulatory network governing diurnal oscillating gene expression is similar between Xiphophorus and other vertebrates for the three Xiphophorus organs tested. In addition, we were able to categorize light responsive gene sets in Xiphophorus that do, and do not, exhibit circadian based oscillating expression patterns. Copyright © 2017 Elsevier Inc. All rights reserved.

Predicting Individual Differences in Placebo Analgesia: Contributions of Brain Activity during Anticipation and Pain Experience

PubMed Central

Wager, Tor D.; Atlas, Lauren Y.; Leotti, Lauren A.; Rilling, James K.

2012-01-01

Recent studies have identified brain correlates of placebo analgesia, but none have assessed how accurately patterns of brain activity can predict individual differences in placebo responses. We reanalyzed data from two fMRI studies of placebo analgesia (N = 47), using patterns of fMRI activity during the anticipation and experience of pain to predict new subjects’ scores on placebo analgesia and placebo-induced changes in pain processing. We used a cross-validated regression procedure, LASSO-PCR, which provided both unbiased estimates of predictive accuracy and interpretable maps of which regions are most important for prediction. Increased anticipatory activity in a frontoparietal network and decreases in a posterior insular/temporal network predicted placebo analgesia. Patterns of anticipatory activity across the cortex predicted a moderate amount of variance in the placebo response (~12% overall, ~40% for study 2 alone), which is substantial considering the multiple likely contributing factors. The most predictive regions were those associated with emotional appraisal, rather than cognitive control or pain processing. During pain, decreases in limbic and paralimbic regions most strongly predicted placebo analgesia. Responses within canonical pain-processing regions explained significant variance in placebo analgesia, but the pattern of effects was inconsistent with widespread decreases in nociceptive processing. Together, the findings suggest that engagement of emotional appraisal circuits drives individual variation in placebo analgesia, rather than early suppression of nociceptive processing. This approach provides a framework that will allow prediction accuracy to increase as new studies provide more precise information for future predictive models. PMID:21228154

Patterns of Brain Activation when Mothers View Their Own Child and Dog: An fMRI Study

PubMed Central

Gollub, Randy L.; Niemi, Steven M.; Evins, Anne Eden

2014-01-01

Neural substrates underlying the human-pet relationship are largely unknown. We examined fMRI brain activation patterns as mothers viewed images of their own child and dog and an unfamiliar child and dog. There was a common network of brain regions involved in emotion, reward, affiliation, visual processing and social cognition when mothers viewed images of both their child and dog. Viewing images of their child resulted in brain activity in the midbrain (ventral tegmental area/substantia nigra involved in reward/affiliation), while a more posterior cortical brain activation pattern involving fusiform gyrus (visual processing of faces and social cognition) characterized a mother's response to her dog. Mothers also rated images of their child and dog as eliciting similar levels of excitement (arousal) and pleasantness (valence), although the difference in the own vs. unfamiliar child comparison was larger than the own vs. unfamiliar dog comparison for arousal. Valence ratings of their dog were also positively correlated with ratings of the attachment to their dog. Although there are similarities in the perceived emotional experience and brain function associated with the mother-child and mother-dog bond, there are also key differences that may reflect variance in the evolutionary course and function of these relationships. PMID:25279788

Patterns of brain activation when mothers view their own child and dog: an fMRI study.

PubMed

Stoeckel, Luke E; Palley, Lori S; Gollub, Randy L; Niemi, Steven M; Evins, Anne Eden

2014-01-01

Neural substrates underlying the human-pet relationship are largely unknown. We examined fMRI brain activation patterns as mothers viewed images of their own child and dog and an unfamiliar child and dog. There was a common network of brain regions involved in emotion, reward, affiliation, visual processing and social cognition when mothers viewed images of both their child and dog. Viewing images of their child resulted in brain activity in the midbrain (ventral tegmental area/substantia nigra involved in reward/affiliation), while a more posterior cortical brain activation pattern involving fusiform gyrus (visual processing of faces and social cognition) characterized a mother's response to her dog. Mothers also rated images of their child and dog as eliciting similar levels of excitement (arousal) and pleasantness (valence), although the difference in the own vs. unfamiliar child comparison was larger than the own vs. unfamiliar dog comparison for arousal. Valence ratings of their dog were also positively correlated with ratings of the attachment to their dog. Although there are similarities in the perceived emotional experience and brain function associated with the mother-child and mother-dog bond, there are also key differences that may reflect variance in the evolutionary course and function of these relationships.

Brain activation in response to randomized visual stimulation as obtained from conjunction and differential analysis: an fMRI study

NASA Astrophysics Data System (ADS)

Nasaruddin, N. H.; Yusoff, A. N.; Kaur, S.

2014-11-01

The objective of this multiple-subjects functional magnetic resonance imaging (fMRI) study was to identify the common brain areas that are activated when viewing black-and-white checkerboard pattern stimuli of various shapes, pattern and size and to investigate specific brain areas that are involved in processing static and moving visual stimuli. Sixteen participants viewed the moving (expanding ring, rotating wedge, flipping hour glass and bowtie and arc quadrant) and static (full checkerboard) stimuli during an fMRI scan. All stimuli have black-and-white checkerboard pattern. Statistical parametric mapping (SPM) was used in generating brain activation. Differential analyses were implemented to separately search for areas involved in processing static and moving stimuli. In general, the stimuli of various shapes, pattern and size activated multiple brain areas mostly in the left hemisphere. The activation in the right middle temporal gyrus (MTG) was found to be significantly higher in processing moving visual stimuli as compared to static stimulus. In contrast, the activation in the left calcarine sulcus and left lingual gyrus were significantly higher for static stimulus as compared to moving stimuli. Visual stimulation of various shapes, pattern and size used in this study indicated left lateralization of activation. The involvement of the right MTG in processing moving visual information was evident from differential analysis, while the left calcarine sulcus and left lingual gyrus are the areas that are involved in the processing of static visual stimulus.

Determination of awareness in patients with severe brain injury using EEG power spectral analysis

PubMed Central

Goldfine, Andrew M.; Victor, Jonathan D.; Conte, Mary M.; Bardin, Jonathan C.; Schiff, Nicholas D.

2011-01-01

Objective To determine whether EEG spectral analysis could be used to demonstrate awareness in patients with severe brain injury. Methods We recorded EEG from healthy controls and three patients with severe brain injury, ranging from minimally conscious state (MCS) to locked-in-state (LIS), while they were asked to imagine motor and spatial navigation tasks. We assessed EEG spectral differences from 4 to 24 Hz with univariate comparisons (individual frequencies) and multivariate comparisons (patterns across the frequency range). Results In controls, EEG spectral power differed at multiple frequency bands and channels during performance of both tasks compared to a resting baseline. As patterns of signal change were inconsistent between controls, we defined a positive response in patient subjects as consistent spectral changes across task performances. One patient in MCS and one in LIS showed evidence of motor imagery task performance, though with patterns of spectral change different from the controls. Conclusion EEG power spectral analysis demonstrates evidence for performance of mental imagery tasks in healthy controls and patients with severe brain injury. Significance EEG power spectral analysis can be used as a flexible bedside tool to demonstrate awareness in brain-injured patients who are otherwise unable to communicate. PMID:21514214

Spread the word: MMN brain response reveals whole-form access of discontinuous particle verbs.

PubMed

Hanna, Jeff; Cappelle, Bert; Pulvermüller, Friedemann

2017-12-01

The status of particle verbs such as rise (…) up as either lexically stored or combinatorially assembled is an issue which so far has not been settled decisively. In this study, we use the mismatch negativity (MMN) brain response to observe neurophysiological responses to discontinuous particle verbs. The MMN can be used to distinguish between whole-form storage and combinatorial processes, as it is enhanced to stored words compared to unknown pseudowords, whereas combinatorially legal strings elicit a reduced MMN relative to ungrammatical ones. Earlier work had found larger MMNs to congruent than to incongruent verb-particle combinations when particle and verb appeared as adjacent elements, thus suggesting whole-form storage at least in this case. However, it is still possible that particle verbs discontinuously spread out across a sentence would elicit the combinatorial, grammar-violation response pattern instead. Here, we tested the brain signatures of discontinuous verb-particle combinations, orthogonally varying congruence and semantic transparency. The results show for the first time brain indices of whole-form storage for discontinuous constituents, thus arguing in favour of access to whole-form-stored lexical elements in the processing of particle verbs, irrespective of their semantic opacity. Results are discussed in the context of linguistic debates about the status of particle verbs as words, lexical elements or syntactically generated combinations. The explanation of the pattern of results within a neurobiological language model is highlighted. Copyright © 2017 Elsevier Inc. All rights reserved.

Weight Perturbation Alters Leptin Signal Transduction in a Region-Specific Manner throughout the Brain

PubMed Central

Morabito, Michael V.; Ravussin, Yann; Mueller, Bridget R.; Skowronski, Alicja A.; Watanabe, Kazuhisa; Foo, Kylie S.; Lee, Samuel X.; Lehmann, Anders; Hjorth, Stephan; Zeltser, Lori M.; LeDuc, Charles A.; Leibel, Rudolph L.

2017-01-01

Diet-induced obesity (DIO) resulting from consumption of a high fat diet (HFD) attenuates normal neuronal responses to leptin and may contribute to the metabolic defense of an acquired higher body weight in humans; the molecular bases for the persistence of this defense are unknown. We measured the responses of 23 brain regions to exogenous leptin in 4 different groups of weight- and/or diet-perturbed mice. Responses to leptin were assessed by quantifying pSTAT3 levels in brain nuclei 30 minutes following 3 mg/kg intraperitoneal leptin. HFD attenuated leptin sensing throughout the brain, but weight loss did not restore central leptin signaling to control levels in several brain regions important in energy homeostasis, including the arcuate and dorsomedial hypothalamic nuclei. Effects of diet on leptin signaling varied by brain region, with results dependent on the method of weight loss (restriction of calories of HFD, ad lib intake of standard mouse chow). High fat diet attenuates leptin signaling throughout the brain, but some brain regions maintain their ability to sense leptin. Weight loss restores leptin sensing to some degree in most (but not all) brain regions, while other brain regions display hypersensitivity to leptin following weight loss. Normal leptin sensing was restored in several brain regions, with the pattern of restoration dependent on the method of weight loss. PMID:28107353

Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression.

PubMed

Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M; Pradhan, Kith; Henn, Fritz A; Shea, Stephen; Osten, Pavel; Li, Bo

2016-01-01

Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP - a marker of neuronal activation - in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing "helpless" behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing "resilient" behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.

Brain Mechanisms Underlying Urge Incontinence and its Response to Pelvic Floor Muscle Training.

PubMed

Griffiths, Derek; Clarkson, Becky; Tadic, Stasa D; Resnick, Neil M

2015-09-01

Urge urinary incontinence is a major problem, especially in the elderly, and to our knowledge the underlying mechanisms of disease and therapy are unknown. We used biofeedback assisted pelvic floor muscle training and functional brain imaging (functional magnetic resonance imaging) to investigate cerebral mechanisms, aiming to improve the understanding of brain-bladder control and therapy. Before receiving biofeedback assisted pelvic floor muscle training functionally intact, older community dwelling women with urge urinary incontinence as well as normal controls underwent comprehensive clinical and bladder diary evaluation, urodynamic testing and brain functional magnetic resonance imaging. Evaluation was repeated after pelvic floor muscle training in those with urge urinary incontinence. Functional magnetic resonance imaging was done to determine the brain reaction to rapid bladder filling with urgency. Of 65 subjects with urge urinary incontinence 28 responded to biofeedback assisted pelvic floor muscle training with 50% or greater improvement of urge urinary incontinence frequency on diary. However, responders and nonresponders displayed 2 patterns of brain reaction. In pattern 1 in responders before pelvic floor muscle training the dorsal anterior cingulate cortex and the adjacent supplementary motor area were activated as well as the insula. After the training dorsal anterior cingulate cortex/supplementary motor area activation diminished and there was a trend toward medial prefrontal cortex deactivation. In pattern 2 in nonresponders before pelvic floor muscle training the medial prefrontal cortex was deactivated, which changed little after the training. In older women with urge urinary incontinence there appears to be 2 patterns of brain reaction to bladder filling and they seem to predict the response and nonresponse to biofeedback assisted pelvic floor muscle training. Moreover, decreased cingulate activation appears to be a consequence of the improvement in urge urinary incontinence induced by training while prefrontal deactivation may be a mechanism contributing to the success of training. In nonresponders the latter mechanism is unavailable, which may explain why another form of therapy is required. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Mapping a multidimensional emotion in response to television commercials.

PubMed

Morris, Jon D; Klahr, Nelson J; Shen, Feng; Villegas, Jorge; Wright, Paul; He, Guojun; Liu, Yijun

2009-03-01

Unlike previous emotional studies using functional neuroimaging that have focused on either locating discrete emotions in the brain or linking emotional response to an external behavior, this study investigated brain regions in order to validate a three-dimensional construct--namely pleasure, arousal, and dominance (PAD) of emotion induced by marketing communication. Emotional responses to five television commercials were measured with Advertisement Self-Assessment Manikins (AdSAM) for PAD and with functional magnetic resonance imaging (fMRI) to identify corresponding patterns of brain activation. We found significant differences in the AdSAM scores on the pleasure and arousal rating scales among the stimuli. Using the AdSAM response as a model for the fMRI image analysis, we showed bilateral activations in the inferior frontal gyri and middle temporal gyri associated with the difference on the pleasure dimension, and activations in the right superior temporal gyrus and right middle frontal gyrus associated with the difference on the arousal dimension. These findings suggest a dimensional approach of constructing emotional changes in the brain and provide a better understanding of human behavior in response to advertising stimuli.

An fMRI study of the brain responses of traumatized mothers to viewing their toddlers during separation and play.

PubMed

Schechter, Daniel S; Moser, Dominik A; Wang, Zhishun; Marsh, Rachel; Hao, XueJun; Duan, Yunsuo; Yu, Shan; Gunter, Benjamin; Murphy, David; McCaw, Jaime; Kangarlu, Alayar; Willheim, Erica; Myers, Michael M; Hofer, Myron A; Peterson, Bradley S

2012-11-01

This study tested whether mothers with interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) vs healthy controls (HC) would show greater limbic and less frontocortical activity when viewing young children during separation compared to quiet play. Mothers of 20 children (12-42 months) participated: 11 IPV-PTSD mothers and 9 HC with no PTSD. During fMRI, mothers watched epochs of play and separation from their own and unfamiliar children. The study focused on comparison of PTSD mothers vs HC viewing children in separation vs play, and viewing own vs unfamiliar children in separation. Both groups showed distinct patterns of brain activation in response to viewing children in separation vs play. PTSD mothers showed greater limbic and less frontocortical activity (BA10) than HC. PTSD mothers also reported feeling more stressed than HC when watching own and unfamiliar children during separation. Their self-reported stress was associated with greater limbic and less frontocortical activity. Both groups also showed distinct patterns of brain activation in response to viewing their own vs unfamiliar children during separation. PTSD mothers' may not have access to frontocortical regulation of limbic response upon seeing own and unfamiliar children in separation. This converges with previously reported associations of maternal IPV-PTSD and atypical caregiving behavior following separation.

Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses

PubMed Central

Low, Lucie A.; Bauer, Lucy C.; Pitcher, Mark H.; Bushnell, M. Catherine

2016-01-01

Abstract With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the “nociceptive” central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli. PMID:27058679

Restraint training for awake functional brain scanning of rodents can cause long-lasting changes in pain and stress responses.

PubMed

Low, Lucie A; Bauer, Lucy C; Pitcher, Mark H; Bushnell, M Catherine

2016-08-01

With the increased interest in longitudinal brain imaging of awake rodents, it is important to understand both the short-term and long-term effects of restraint on sensory and emotional processing in the brain. To understand the effects of repeated restraint on pain behaviors and stress responses, we modeled a restraint protocol similar to those used to habituate rodents for magnetic resonance imaging scanning, and studied sensory sensitivity and stress hormone responses over 5 days. To uncover lasting effects of training, we also looked at responses to the formalin pain test 2 weeks later. We found that while restraint causes acute increases in the stress hormone corticosterone, it can also cause lasting reductions in nociceptive behavior in the formalin test, coupled with heightened corticosterone levels and increased activation of the "nociceptive" central nucleus of the amygdala, as seen by Fos protein expression. These results suggest that short-term repeated restraint, similar to that used to habituate rats for awake functional brain scanning, could potentially cause long-lasting changes in physiological and brain responses to pain stimuli that are stress-related, and therefore could potentially confound the functional activation patterns seen in awake rodents in response to pain stimuli.

Different types of theta rhythmicity are induced by social and fearful stimuli in a network associated with social memory.

PubMed

Tendler, Alex; Wagner, Shlomo

2015-02-16

Rhythmic activity in the theta range is thought to promote neuronal communication between brain regions. In this study, we performed chronic telemetric recordings in socially behaving rats to monitor electrophysiological activity in limbic brain regions linked to social behavior. Social encounters were associated with increased rhythmicity in the high theta range (7-10 Hz) that was proportional to the stimulus degree of novelty. This modulation of theta rhythmicity, which was specific for social stimuli, appeared to reflect a brain-state of social arousal. In contrast, the same network responded to a fearful stimulus by enhancement of rhythmicity in the low theta range (3-7 Hz). Moreover, theta rhythmicity showed different pattern of coherence between the distinct brain regions in response to social and fearful stimuli. We suggest that the two types of stimuli induce distinct arousal states that elicit different patterns of theta rhythmicity, which cause the same brain areas to communicate in different modes.

Familiarity and Recollection Produce Distinct Eye Movement, Pupil and Medial Temporal Lobe Responses when Memory Strength Is Matched

ERIC Educational Resources Information Center

Kafkas, Alexandros; Montaldi, Daniela

2012-01-01

Two experiments explored eye measures (fixations and pupil response patterns) and brain responses (BOLD) accompanying the recognition of visual object stimuli based on familiarity and recollection. In both experiments, the use of a modified remember/know procedure led to high confidence and matched accuracy levels characterising strong familiarity…

Oscillatory frontal theta responses are increased upon bisensory stimulation.

PubMed

Sakowitz, O W; Schürmann, M; Başar, E

2000-05-01

To investigate the functional correlation of oscillatory EEG components with the interaction of sensory modalities following simultaneous audio-visual stimulation. In an experimental study (15 subjects) we compared auditory evoked potentials (AEPs) and visual evoked potentials (VEPs) to bimodal evoked potentials (BEPs; simultaneous auditory and visual stimulation). BEPs were assumed to be brain responses to complex stimuli as a marker for intermodal associative functioning. Frequency domain analysis of these EPs showed marked theta-range components in response to bimodal stimulation. These theta components could not be explained by linear addition of the unimodal responses in the time domain. Considering topography the increased theta-response showed a remarkable frontality in proximity to multimodal association cortices. Referring to methodology we try to demonstrate that, even if various behavioral correlates of brain oscillations exist, common patterns can be extracted by means of a systems-theoretical approach. Serving as an example of functionally relevant brain oscillations, theta responses could be interpreted as an indicator of associative information processing.

Transcallosal transfer of information and functional asymmetry of the human brain.

PubMed

Nowicka, Anna; Tacikowski, Pawel

2011-01-01

The corpus callosum is the largest commissure in the brain and acts as a "bridge" of nerve fibres connecting the two cerebral hemispheres. It plays a crucial role in interhemispheric integration and is responsible for normal communication and cooperation between the two hemispheres. Evolutionary pressures guiding brain size are accompanied by reduced interhemispheric and enhanced intrahemispheric connectivity. Some lines of evidence suggest that the speed of transcallosal conduction is limited in large brains (e.g., in humans), thus favouring intrahemispheric processing and brain lateralisation. Patterns of directional symmetry/asymmetry of transcallosal transfer time may be related to the degree of brain lateralisation. Neural network modelling and electrophysiological studies on interhemispheric transmission provide data supporting this supposition.

Patterns of brain and cardiovascular activation while solving rule-discovery and rule-application numeric tasks.

PubMed

Sosnowski, Tytus; Rynkiewicz, Andrzej; Wordecha, Małgorzata; Kępkowicz, Anna; Majewska, Adrianna; Pstrągowska, Aleksandra; Oleksy, Tomasz; Wypych, Marek; Marchewka, Artur

2017-07-01

It is known that solving mental tasks leads to tonic increase in cardiovascular activity. Our previous research showed that tasks involving rule application (RA) caused greater tonic increase in cardiovascular activity than tasks requiring rule discovery (RD). However, it is not clear what brain mechanisms are responsible for this difference. The aim of two experimental studies was to compare the patterns of brain and cardiovascular activity while both RD and the RA numeric tasks were being solved. The fMRI study revealed greater brain activation while solving RD tasks than while solving RA tasks. In particular, RD tasks evoked greater activation of the left inferior frontal gyrus and selected areas in the parietal, and temporal cortices, including the precuneus, supramarginal gyrus, angular gyrus, inferior parietal lobule, and the superior temporal gyrus, and the cingulate cortex. In addition, RA tasks caused larger increases in HR than RD tasks. The second study, carried out in a cardiovascular laboratory, showed greater increases in heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) while solving RA tasks than while solving RD tasks. The results support the hypothesis that RD and RA tasks involve different modes of information processing, but the neuronal mechanism responsible for the observed greater cardiovascular response to RA tasks than to RD tasks is not completely clear. Copyright © 2017. Published by Elsevier B.V.

Revisiting the cognitive buffer hypothesis for the evolution of large brains

PubMed Central

Sol, Daniel

2008-01-01

Why have some animals evolved large brains despite substantial energetic and developmental costs? A classic answer is that a large brain facilitates the construction of behavioural responses to unusual, novel or complex socioecological challenges. This buffer effect should increase survival rates and favour a longer reproductive life, thereby compensating for the costs of delayed reproduction. Although still limited, evidence in birds and mammals is accumulating that a large brain facilitates the construction of novel and altered behavioural patterns and that this ability helps dealing with new ecological challenges more successfully, supporting the cognitive-buffer interpretation of the evolution of large brains. PMID:19049952

Neural patterning of human induced pluripotent stem cells in 3-D cultures for studying biomolecule-directed differential cellular responses.

PubMed

Yan, Yuanwei; Bejoy, Julie; Xia, Junfei; Guan, Jingjiao; Zhou, Yi; Li, Yan

2016-09-15

Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells/tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capacity of signaling factors that regulate 3-D neural tissue patterning in vitro and differential responses of the resulting neural populations to various biomolecules have not yet been fully understood. By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog (SHH) signaling, this study generated different 3-D neuronal cultures that were mainly comprised of either cortical glutamatergic neurons or motor neurons. Abundant glutamatergic neurons were observed following the treatment with an antagonist of SHH signaling, cyclopamine, while Islet-1 and HB9-expressing motor neurons were enriched by an SHH agonist, purmorphamine. In neurons derived with different neural patterning factors, whole-cell patch clamp recordings showed similar voltage-gated Na(+)/K(+) currents, depolarization-evoked action potentials and spontaneous excitatory post-synaptic currents. Moreover, these different neuronal populations exhibited differential responses to three classes of biomolecules, including (1) matrix metalloproteinase inhibitors that affect extracellular matrix remodeling; (2) N-methyl-d-aspartate that induces general neurotoxicity; and (3) amyloid β (1-42) oligomers that cause neuronal subtype-specific neurotoxicity. This study should advance our understanding of hiPSC self-organization and neural tissue development and provide a transformative approach to establish 3-D models for neurological disease modeling and drug discovery. Appropriate neural patterning of human induced pluripotent stem cells (hiPSCs) is critical to generate specific neural cells, tissues and even mini-brains that are physiologically relevant to model neurological diseases. However, the capability of sonic hedgehog-related small molecules to tune different neuronal subtypes in 3-D differentiation from hiPSCs and the differential cellular responses of region-specific neuronal subtypes to various biomolecules have not been fully investigated. By tuning neural patterning of hiPSCs with small molecules targeting sonic hedgehog signaling, this study provides knowledge on the differential susceptibility of region-specific neuronal subtypes derived from hiPSCs to different biomolecules in extracellular matrix remodeling and neurotoxicity. The findings are significant for understanding 3-D neural patterning of hiPSCs for the applications in brain organoid formation, neurological disease modeling, and drug discovery. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Patterns of neural activity associated with differential acute locomotor stimulation to cocaine and methamphetamine in adolescent versus adult male C57BL/6J mice

PubMed Central

Zombeck, Jonathan A.; Lewicki, Aaron D.; Patel, Kevin; Gupta, Tripta; Rhodes, Justin S.

2009-01-01

Adolescence is a time period when major changes occur in the brain with long-term consequences for behavior. One ramification is altered responses to drugs of abuse, but the specific brain mechanisms and implications for mental health are poorly understood. Here, we used a mouse model in which adolescents display dramatically reduced sensitivity to the acute locomotor stimulating effects of cocaine and methamphetamine. The goal was to identify key brain regions or circuits involved in the differential behavior. Male adolescent (PN 30–35) and young adult (PN 69–74) C57BL/6J mice were administered an intraperitoneal injection of cocaine (0, 15, 30 mg/kg) or methamphetamine (0, 2, 4 mg/kg) and euthanized 90 minutes later. Locomotor activity was monitored continuously in the home cage by video tracking. Immunohistochemical detection of Fos protein was used to quantify neuronal activation in 16 different brain regions. As expected, adolescents were less sensitive to the locomotor stimulating effects of cocaine and methamphetamine as indicated by a rightward shift in the dose response relationship. After a saline injection, adolescents showed similar levels of Fos as adults in all regions except the dorsal and lateral caudate where levels were lower in adolescents. Cocaine and methamphetamine dose dependently increased Fos in all brain regions sampled in both adolescents and adults, but Fos levels were similar in both age groups for a majority of regions and doses. Locomotor activity was correlated with Fos in several brain areas within adolescent and adult groups, and adolescents had a significantly greater induction of Fos for a given amount of locomotor activity in key brain regions including the caudate where they showed reduced Fos under baseline conditions. Future research will identify the molecular and cellular events that are responsible for the differential psychostimulant-induced patterns of brain activation and behavior observed in adolescent versus adult mice. PMID:19932887

Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress.

PubMed

Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Cooper, Sarah; Gajewski, Paula; Eagle, Andrew; Mazei-Robison, Michelle; Nestler, Eric J; Robison, A J

2015-12-01

Major depressive disorder is thought to arise in part from dysfunction of the brain's "reward circuitry", consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression--the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus--in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 h following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Fiber Bragg grating sensor-based communication assistance device

NASA Astrophysics Data System (ADS)

Padma, Srivani; Umesh, Sharath; Pant, Shweta; Srinivas, Talabattula; Asokan, Sundarrajan

2016-08-01

Improvements in emergency medicine in the form of efficient life supporting systems and intensive care have increased the survival rate in critically injured patients; however, in some cases, severe brain and spinal cord injuries can result in a locked-in syndrome or other forms of paralysis, and communication with these patients may become restricted or impossible. The present study proposes a noninvasive, real-time communication assistive methodology for those with restricted communication ability, employing a fiber Bragg grating (FBG) sensor. The communication assistive methodology comprises a breath pattern analyzer using an FBG sensor, which acquires the exhalation force that is converted into strain variations on a cantilever. The FBG breath pattern analyzer along with specific breath patterns, which are programmed to give specific audio output commands, constitutes the proposed fiber Bragg grating sensor-based communication assistive device. The basic communication can be carried out by instructing the patients with restricted communication ability to perform the specific breath patterns. The present approach is intended to be an alternative to the common approach of brain-computer interface in which an instrument is utilized for learning of brain responses.

Experiential, Autonomic, and Neural Responses During Threat Anticipation Vary as a Function of Threat Intensity and Neuroticism

PubMed Central

Drabant, Emily M; Kuo, Janice R; Ramel, Wiveka; Blechert, Jens; Edge, Michael D; Cooper, Jeff R; Goldin, Philippe R; Hariri, Ahmad R; Gross, James J

2011-01-01

Anticipatory emotional responses play a crucial role in preparing individuals for impending challenges. They do this by triggering a coordinated set of changes in behavioral, autonomic, and neural response systems. In the present study, we examined the biobehavioral impact of varying levels of anticipatory anxiety, using a shock anticipation task in which unpredictable electric shocks were threatened and delivered to the wrist at variable intervals and intensities (safe, medium, strong). This permitted investigation of a dynamic range of anticipatory anxiety responses. In two studies, 95 and 51 healthy female participants, respectively, underwent this shock anticipation task while providing continuous ratings of anxiety experience and electrodermal responding (Study 1) and during fMRI BOLD neuroimaging (Study 2). Results indicated a step-wise pattern of responding in anxiety experience and electrodermal responses. Several brain regions showed robust responses to shock anticipation relative to safe trials, including the hypothalamus, periaqueductal gray, caudate, precentral gyrus, thalamus, insula, ventrolateral PFC, dorsomedial PFC, and ACC. A subset of these regions demonstrated a linear pattern of increased responding from safe to medium to strong trials, including the bilateral insula, ACC, and inferior frontal gyrus. These responses were modulated by individual differences in neuroticism, such that those high in neuroticism showed exaggerated anxiety experience across the entire task, and reduced brain activation from medium to strong trials in a subset of brain regions. These findings suggest that individual differences in neuroticism may influence sensitivity to anticipatory threat and provide new insights into the mechanism through which neuroticism may confer risk for developing anxiety disorders via dysregulated anticipatory responses. PMID:21093595

Simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo

PubMed Central

Hirai, Yasuharu; Nishino, Eri

2015-01-01

Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices. PMID:25761950

Simultaneous recording of fluorescence and electrical signals by photometric patch electrode in deep brain regions in vivo.

PubMed

Hirai, Yasuharu; Nishino, Eri; Ohmori, Harunori

2015-06-01

Despite its widespread use, high-resolution imaging with multiphoton microscopy to record neuronal signals in vivo is limited to the surface of brain tissue because of limited light penetration. Moreover, most imaging studies do not simultaneously record electrical neural activity, which is, however, crucial to understanding brain function. Accordingly, we developed a photometric patch electrode (PME) to overcome the depth limitation of optical measurements and also enable the simultaneous recording of neural electrical responses in deep brain regions. The PME recoding system uses a patch electrode to excite a fluorescent dye and to measure the fluorescence signal as a light guide, to record electrical signal, and to apply chemicals to the recorded cells locally. The optical signal was analyzed by either a spectrometer of high light sensitivity or a photomultiplier tube depending on the kinetics of the responses. We used the PME in Oregon Green BAPTA-1 AM-loaded avian auditory nuclei in vivo to monitor calcium signals and electrical responses. We demonstrated distinct response patterns in three different nuclei of the ascending auditory pathway. On acoustic stimulation, a robust calcium fluorescence response occurred in auditory cortex (field L) neurons that outlasted the electrical response. In the auditory midbrain (inferior colliculus), both responses were transient. In the brain-stem cochlear nucleus magnocellularis, calcium response seemed to be effectively suppressed by the activity of metabotropic glutamate receptors. In conclusion, the PME provides a powerful tool to study brain function in vivo at a tissue depth inaccessible to conventional imaging devices. Copyright © 2015 the American Physiological Society.

Rough Set Based Splitting Criterion for Binary Decision Tree Classifiers

DTIC Science & Technology

2006-09-26

Alata O. Fernandez-Maloigne C., and Ferrie J.C. (2001). Unsupervised Algorithm for the Segmentation of Three-Dimensional Magnetic Resonance Brain ...instinctual and learned responses in the brain , causing it to make decisions based on patterns in the stimuli. Using this deceptively simple process...2001. [2] Bohn C. (1997). An Incremental Unsupervised Learning Scheme for Function Approximation. In: Proceedings of the 1997 IEEE International

Multichannel activity propagation across an engineered axon network

NASA Astrophysics Data System (ADS)

Chen, H. Isaac; Wolf, John A.; Smith, Douglas H.

2017-04-01

Objective. Although substantial progress has been made in mapping the connections of the brain, less is known about how this organization translates into brain function. In particular, the massive interconnectivity of the brain has made it difficult to specifically examine data transmission between two nodes of the connectome, a central component of the ‘neural code.’ Here, we investigated the propagation of multiple streams of asynchronous neuronal activity across an isolated in vitro ‘connectome unit.’ Approach. We used the novel technique of axon stretch growth to create a model of a long-range cortico-cortical network, a modular system consisting of paired nodes of cortical neurons connected by axon tracts. Using optical stimulation and multi-electrode array recording techniques, we explored how input patterns are represented by cortical networks, how these representations shift as they are transmitted between cortical nodes and perturbed by external conditions, and how well the downstream node distinguishes different patterns. Main results. Stimulus representations included direct, synaptic, and multiplexed responses that grew in complexity as the distance between the stimulation source and recorded neuron increased. These representations collapsed into patterns with lower information content at higher stimulation frequencies. With internodal activity propagation, a hierarchy of network pathways, including latent circuits, was revealed using glutamatergic blockade. As stimulus channels were added, divergent, non-linear effects were observed in local versus distant network layers. Pairwise difference analysis of neuronal responses suggested that neuronal ensembles generally outperformed individual cells in discriminating input patterns. Significance. Our data illuminate the complexity of spiking activity propagation in cortical networks in vitro, which is characterized by the transformation of an input into myriad outputs over several network layers. These results provide insight into how the brain potentially processes information and generates the neural code and could guide the development of clinical therapies based on multichannel brain stimulation.

Enhancing health leadership performance using neurotherapy.

PubMed

Swingle, Paul G; Hartney, Elizabeth

2018-05-01

The discovery of neuroplasticity means the brain can change, functionally, in response to the environment and to learning. While individuals can develop harmful patterns of brain activity in response to stressors, they can also learn to modify or control neurological conditions associated with specific behaviors. Neurotherapy is one way of changing brain functioning to modify troubling conditions which can impair leadership performance, through responding to feedback on their own brain activity, and enhancing optimal leadership functioning through learning to maximize such cognitive strengths as mental efficiency, focus, creativity, perseverance, and executive functioning. The present article outlines the application of the concept of optimal performance training to organizational leadership in a healthcare context, by describing approaches to neurotherapy and illustrating their application through a case study of a health leader learning to overcome the neurological and emotional sequelae of workplace stress and trauma.

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

PubMed

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

2018-05-01

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

Neurovascular coupling and energy metabolism in the developing brain

PubMed Central

Kozberg, M.; Hillman, E.

2016-01-01

In the adult brain, increases in local neural activity are almost always accompanied by increases in local blood flow. However, many functional imaging studies of the newborn and developing human brain have observed patterns of hemodynamic responses that differ from adult responses. Among the proposed mechanisms for the observed variations is that neurovascular coupling itself is still developing in the perinatal brain. Many of the components thought to be involved in actuating and propagating this hemodynamic response are known to still be developing postnatally, including perivascular cells such as astrocytes and pericytes. Both neural and vascular networks expand and are then selectively pruned over the first year of human life. Additionally, the metabolic demands of the newborn brain are still evolving. These changes are highly likely to affect early postnatal neurovascular coupling, and thus may affect functional imaging signals in this age group. This chapter will discuss the literature relating to neurovascular development. Potential effects of normal and aberrant development of neurovascular coupling on the newborn brain will also be explored, as well as ways to effectively utilize imaging techniques that rely on hemodynamic modulation such as fMRI and NIRS in younger populations. PMID:27130418

Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

PubMed

Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

2015-01-01

The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

Modulation of the adaptive response to stress by brain activation of selective somatostatin receptor subtypes.

PubMed

Stengel, Andreas; Rivier, Jean; Taché, Yvette

2013-04-01

Somatostatin-14 was discovered in 1973 in the hypothalamus as a peptide inhibiting growth hormone release. Somatostatin interacts with five receptor subtypes (sst(1-5)) which are widely distributed in the brain with a distinct, but overlapping, expression pattern. During the last few years, the development of highly selective peptide agonists and antagonists provided new insight to characterize the role of somatostatin receptor subtypes in the pleiotropic actions of somatostatin. Recent evidence in rodents indicates that the activation of selective somatostatin receptor subtypes in the brain blunts stress-corticotropin-releasing factor (CRF) related ACTH release (sst2/5), sympathetic-adrenal activaton (sst5), stimulation of colonic motility (sst1), delayed gastric emptying (sst5), suppression of food intake (sst2) and the anxiogenic-like (sst2) response. These findings suggest that brain somatostatin signaling pathways may play an important role in dampening CRF-mediated endocrine, sympathetic, behavioral and visceral responses to stress. Published by Elsevier Inc.

Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression

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

Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M.

Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP – a marker of neuronal activation – in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing “helpless” behavior had an overall brain-wide reduction in the level ofmore » neuronal activation compared with mice showing “resilient” behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. In conclusion, our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses tostress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.« less

Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression

DOE PAGES

Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M.; ...

2016-02-03

Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP – a marker of neuronal activation – in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing “helpless” behavior had an overall brain-wide reduction in the level ofmore » neuronal activation compared with mice showing “resilient” behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. In conclusion, our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses tostress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses.« less

Whole-Brain Mapping of Neuronal Activity in the Learned Helplessness Model of Depression

PubMed Central

Kim, Yongsoo; Perova, Zinaida; Mirrione, Martine M.; Pradhan, Kith; Henn, Fritz A.; Shea, Stephen; Osten, Pavel; Li, Bo

2016-01-01

Some individuals are resilient, whereas others succumb to despair in repeated stressful situations. The neurobiological mechanisms underlying such divergent behavioral responses remain unclear. Here, we employed an automated method for mapping neuronal activity in search of signatures of stress responses in the entire mouse brain. We used serial two-photon tomography to detect expression of c-FosGFP – a marker of neuronal activation – in c-fosGFP transgenic mice subjected to the learned helplessness (LH) procedure, a widely used model of stress-induced depression-like phenotype in laboratory animals. We found that mice showing “helpless” behavior had an overall brain-wide reduction in the level of neuronal activation compared with mice showing “resilient” behavior, with the exception of a few brain areas, including the locus coeruleus, that were more activated in the helpless mice. In addition, the helpless mice showed a strong trend of having higher similarity in whole-brain activity profile among individuals, suggesting that helplessness is represented by a more stereotypic brain-wide activation pattern. This latter effect was confirmed in rats subjected to the LH procedure, using 2-deoxy-2[18F]fluoro-D-glucose positron emission tomography to assess neural activity. Our findings reveal distinct brain activity markings that correlate with adaptive and maladaptive behavioral responses to stress, and provide a framework for further studies investigating the contribution of specific brain regions to maladaptive stress responses. PMID:26869888

Site specificity of adrenalectomy-induced brain growth.

PubMed

Thomas, T L; Devenport, L D

1988-12-01

Infant, juvenile, and adult brain growth is modulated by corticosterone. This study was designed to determine whether such modulation is confined to certain specific brain areas, and if the pattern of growth revealed is consistent across strains of rats. Young female Sprague-Dawley-derived rats were either adrenalectomized (ADX) or sham-operated (Sham) and allowed to mature 45 days before they were sacrificed for histological analysis. Fore brain sections were taken at several planes for display by projection microscope. Of the 21 sites examined, ADX exerted its greatest effect upon neocortical tissue and myelinated fiber tracts. The only other brain region affected was thalamus, which exhibited a significant widening as a result of ADX. In contrast, archicortical structures were notably unaffected by ADX. Neither the hippocampus, measured from a variety of planes, nor nuclei in the septal area were subject to increased growth by ADX. This general portrayal of ADX's site specificity held across strains of rats. However, there were local differences. Within the neopallium, the frontal region underwent the greatest thickening in one strain, while the occipital area was most strongly affected in the other. Parietal cortex was equally responsive in both strains. The pattern of sensitive vs insensitive sites bore a resemblance to the pattern of increased growth brought about by environmental enrichment as well as the fore brain distribution of Type 2 corticosterone receptors.

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

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.

A dynamical pattern recognition model of gamma activity in auditory cortex

PubMed Central

Zavaglia, M.; Canolty, R.T.; Schofield, T.M.; Leff, A.P.; Ursino, M.; Knight, R.T.; Penny, W.D.

2012-01-01

This paper describes a dynamical process which serves both as a model of temporal pattern recognition in the brain and as a forward model of neuroimaging data. This process is considered at two separate levels of analysis: the algorithmic and implementation levels. At an algorithmic level, recognition is based on the use of Occurrence Time features. Using a speech digit database we show that for noisy recognition environments, these features rival standard cepstral coefficient features. At an implementation level, the model is defined using a Weakly Coupled Oscillator (WCO) framework and uses a transient synchronization mechanism to signal a recognition event. In a second set of experiments, we use the strength of the synchronization event to predict the high gamma (75–150 Hz) activity produced by the brain in response to word versus non-word stimuli. Quantitative model fits allow us to make inferences about parameters governing pattern recognition dynamics in the brain. PMID:22327049

Voluntary Enhancement of Neural Signatures of Affiliative Emotion Using fMRI Neurofeedback

PubMed Central

Moll, Jorge; Weingartner, Julie H.; Bado, Patricia; Basilio, Rodrigo; Sato, João R.; Melo, Bruno R.; Bramati, Ivanei E.; de Oliveira-Souza, Ricardo; Zahn, Roland

2014-01-01

In Ridley Scott’s film “Blade Runner”, empathy-detection devices are employed to measure affiliative emotions. Despite recent neurocomputational advances, it is unknown whether brain signatures of affiliative emotions, such as tenderness/affection, can be decoded and voluntarily modulated. Here, we employed multivariate voxel pattern analysis and real-time fMRI to address this question. We found that participants were able to use visual feedback based on decoded fMRI patterns as a neurofeedback signal to increase brain activation characteristic of tenderness/affection relative to pride, an equally complex control emotion. Such improvement was not observed in a control group performing the same fMRI task without neurofeedback. Furthermore, the neurofeedback-driven enhancement of tenderness/affection-related distributed patterns was associated with local fMRI responses in the septohypothalamic area and frontopolar cortex, regions previously implicated in affiliative emotion. This demonstrates that humans can voluntarily enhance brain signatures of tenderness/affection, unlocking new possibilities for promoting prosocial emotions and countering antisocial behavior. PMID:24847819

Sex hormones affect acute and chronic stress responses in sexually dimorphic patterns: Consequences for depression models.

PubMed

Guo, Lei; Chen, Yi-Xi; Hu, Yu-Ting; Wu, Xue-Yan; He, Yang; Wu, Juan-Li; Huang, Man-Li; Mason, Matthew; Bao, Ai-Min

2018-05-21

Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules. Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids. Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes. Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences. Copyright © 2018 Elsevier Ltd. All rights reserved.

An fMRI study of the brain responses of traumatized mothers to viewing their toddlers during separation and play

PubMed Central

Moser, Dominik A.; Wang, Zhishun; Marsh, Rachel; Hao, XueJun; Duan, Yunsuo; Yu, Shan; Gunter, Benjamin; Murphy, David; McCaw, Jaime; Kangarlu, Alayar; Willheim, Erica; Myers, Michael M.; Hofer, Myron A.; Peterson, Bradley S.

2012-01-01

This study tested whether mothers with interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) vs healthy controls (HC) would show greater limbic and less frontocortical activity when viewing young children during separation compared to quiet play. Mothers of 20 children (12–42 months) participated: 11 IPV-PTSD mothers and 9 HC with no PTSD. During fMRI, mothers watched epochs of play and separation from their own and unfamiliar children. The study focused on comparison of PTSD mothers vs HC viewing children in separation vs play, and viewing own vs unfamiliar children in separation. Both groups showed distinct patterns of brain activation in response to viewing children in separation vs play. PTSD mothers showed greater limbic and less frontocortical activity (BA10) than HC. PTSD mothers also reported feeling more stressed than HC when watching own and unfamiliar children during separation. Their self-reported stress was associated with greater limbic and less frontocortical activity. Both groups also showed distinct patterns of brain activation in response to viewing their own vs unfamiliar children during separation. PTSD mothers’ may not have access to frontocortical regulation of limbic response upon seeing own and unfamiliar children in separation. This converges with previously reported associations of maternal IPV-PTSD and atypical caregiving behavior following separation. PMID:22021653

Genomic responses in rat cerebral cortex after traumatic brain injury

PubMed Central

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

2005-01-01

Background Traumatic brain injury (TBI) initiates a complex sequence of destructive and neuroprotective cellular responses. The initial mechanical injury is followed by an extended time period of secondary brain damage. Due to the complicated pathological picture a better understanding of the molecular events occurring during this secondary phase of injury is needed. This study was aimed at analysing gene expression patterns following cerebral cortical contusion in rat using high throughput microarray technology with the goal of identifying genes involved in an early and in a more delayed phase of trauma, as genomic responses behind secondary mechanisms likely are time-dependent. Results Among the upregulated genes 1 day post injury, were transcription factors and genes involved in metabolism, e.g. STAT-3, C/EBP-δ and cytochrome p450. At 4 days post injury we observed increased gene expression of inflammatory factors, proteases and their inhibitors, like cathepsins, α-2-macroglobulin and C1q. Notably, genes with biological function clustered to immune response were significantly upregulated 4 days after injury, which was not found following 1 day. Osteopontin and one of its receptors, CD-44, were both upregulated showing a local mRNA- and immunoreactivity pattern in and around the injury site. Fewer genes had decreased expression both 1 and 4 days post injury and included genes implicated in transport, metabolism, signalling, and extra cellular matrix formation, e.g. vitronectin, neuroserpin and angiotensinogen. Conclusion The different patterns of gene expression, with little overlap in genes, 1 and 4 days post injury showed time dependence in genomic responses to trauma. An early induction of factors involved in transcription could lead to the later inflammatory response with strongly upregulated CD-44 and osteopontin expression. An increased knowledge of genes regulating the pathological mechanisms in trauma will help to find future treatment targets. Since trauma is a risk factor for development of neurodegenerative disease, this knowledge may also reduce late negative effects. PMID:16318630

Image Statistics and the Representation of Material Properties in the Visual Cortex

PubMed Central

Baumgartner, Elisabeth; Gegenfurtner, Karl R.

2016-01-01

We explored perceived material properties (roughness, texturedness, and hardness) with a novel approach that compares perception, image statistics and brain activation, as measured with fMRI. We initially asked participants to rate 84 material images with respect to the above mentioned properties, and then scanned 15 of the participants with fMRI while they viewed the material images. The images were analyzed with a set of image statistics capturing their spatial frequency and texture properties. Linear classifiers were then applied to the image statistics as well as the voxel patterns of visually responsive voxels and early visual areas to discriminate between images with high and low perceptual ratings. Roughness and texturedness could be classified above chance level based on image statistics. Roughness and texturedness could also be classified based on the brain activation patterns in visual cortex, whereas hardness could not. Importantly, the agreement in classification based on image statistics and brain activation was also above chance level. Our results show that information about visual material properties is to a large degree contained in low-level image statistics, and that these image statistics are also partially reflected in brain activity patterns induced by the perception of material images. PMID:27582714

Image Statistics and the Representation of Material Properties in the Visual Cortex.

PubMed

Baumgartner, Elisabeth; Gegenfurtner, Karl R

2016-01-01

We explored perceived material properties (roughness, texturedness, and hardness) with a novel approach that compares perception, image statistics and brain activation, as measured with fMRI. We initially asked participants to rate 84 material images with respect to the above mentioned properties, and then scanned 15 of the participants with fMRI while they viewed the material images. The images were analyzed with a set of image statistics capturing their spatial frequency and texture properties. Linear classifiers were then applied to the image statistics as well as the voxel patterns of visually responsive voxels and early visual areas to discriminate between images with high and low perceptual ratings. Roughness and texturedness could be classified above chance level based on image statistics. Roughness and texturedness could also be classified based on the brain activation patterns in visual cortex, whereas hardness could not. Importantly, the agreement in classification based on image statistics and brain activation was also above chance level. Our results show that information about visual material properties is to a large degree contained in low-level image statistics, and that these image statistics are also partially reflected in brain activity patterns induced by the perception of material images.

Analysis and asynchronous detection of gradually unfolding errors during monitoring tasks

NASA Astrophysics Data System (ADS)

Omedes, Jason; Iturrate, Iñaki; Minguez, Javier; Montesano, Luis

2015-10-01

Human studies on cognitive control processes rely on tasks involving sudden-onset stimuli, which allow the analysis of these neural imprints to be time-locked and relative to the stimuli onset. Human perceptual decisions, however, comprise continuous processes where evidence accumulates until reaching a boundary. Surpassing the boundary leads to a decision where measured brain responses are associated to an internal, unknown onset. The lack of this onset for gradual stimuli hinders both the analyses of brain activity and the training of detectors. This paper studies electroencephalographic (EEG)-measurable signatures of human processing for sudden and gradual cognitive processes represented as a trajectory mismatch under a monitoring task. Time-locked potentials and brain-source analysis of the EEG of sudden mismatches revealed the typical components of event-related potentials and the involvement of brain structures related to cognitive control processing. For gradual mismatch events, time-locked analyses did not show any discernible EEG scalp pattern, despite related brain areas being, to a lesser extent, activated. However, and thanks to the use of non-linear pattern recognition algorithms, it is possible to train an asynchronous detector on sudden events and use it to detect gradual mismatches, as well as obtaining an estimate of their unknown onset. Post-hoc time-locked scalp and brain-source analyses revealed that the EEG patterns of detected gradual mismatches originated in brain areas related to cognitive control processing. This indicates that gradual events induce latency in the evaluation process but that similar brain mechanisms are present in sudden and gradual mismatch events. Furthermore, the proposed asynchronous detection model widens the scope of applications of brain-machine interfaces to other gradual processes.

Relationship of Topology, Multiscale Phase Synchronization, and State Transitions in Human Brain Networks

PubMed Central

Kim, Minkyung; Kim, Seunghwan; Mashour, George A.; Lee, UnCheol

2017-01-01

How the brain reconstitutes consciousness and cognition after a major perturbation like general anesthesia is an important question with significant neuroscientific and clinical implications. Recent empirical studies in animals and humans suggest that the recovery of consciousness after anesthesia is not random but ordered. Emergence patterns have been classified as progressive and abrupt transitions from anesthesia to consciousness, with associated differences in duration and electroencephalogram (EEG) properties. We hypothesized that the progressive and abrupt emergence patterns from the unconscious state are associated with, respectively, continuous and discontinuous synchronization transitions in functional brain networks. The discontinuous transition is explainable with the concept of explosive synchronization, which has been studied almost exclusively in network science. We used the Kuramato model, a simple oscillatory network model, to simulate progressive and abrupt transitions in anatomical human brain networks acquired from diffusion tensor imaging (DTI) of 82 brain regions. To facilitate explosive synchronization, distinct frequencies for hub nodes with a large frequency disassortativity (i.e., higher frequency nodes linking with lower frequency nodes, or vice versa) were applied to the brain network. In this simulation study, we demonstrated that both progressive and abrupt transitions follow distinct synchronization processes at the individual node, cluster, and global network levels. The characteristic synchronization patterns of brain regions that are “progressive and earlier” or “abrupt but delayed” account for previously reported behavioral responses of gradual and abrupt emergence from the unconscious state. The characteristic network synchronization processes observed at different scales provide new insights into how regional brain functions are reconstituted during progressive and abrupt emergence from the unconscious state. This theoretical approach also offers a principled explanation of how the brain reconstitutes consciousness and cognitive functions after physiologic (sleep), pharmacologic (anesthesia), and pathologic (coma) perturbations. PMID:28713258

Relationship of Topology, Multiscale Phase Synchronization, and State Transitions in Human Brain Networks.

PubMed

Kim, Minkyung; Kim, Seunghwan; Mashour, George A; Lee, UnCheol

2017-01-01

How the brain reconstitutes consciousness and cognition after a major perturbation like general anesthesia is an important question with significant neuroscientific and clinical implications. Recent empirical studies in animals and humans suggest that the recovery of consciousness after anesthesia is not random but ordered. Emergence patterns have been classified as progressive and abrupt transitions from anesthesia to consciousness, with associated differences in duration and electroencephalogram (EEG) properties. We hypothesized that the progressive and abrupt emergence patterns from the unconscious state are associated with, respectively, continuous and discontinuous synchronization transitions in functional brain networks. The discontinuous transition is explainable with the concept of explosive synchronization, which has been studied almost exclusively in network science. We used the Kuramato model, a simple oscillatory network model, to simulate progressive and abrupt transitions in anatomical human brain networks acquired from diffusion tensor imaging (DTI) of 82 brain regions. To facilitate explosive synchronization, distinct frequencies for hub nodes with a large frequency disassortativity (i.e., higher frequency nodes linking with lower frequency nodes, or vice versa) were applied to the brain network. In this simulation study, we demonstrated that both progressive and abrupt transitions follow distinct synchronization processes at the individual node, cluster, and global network levels. The characteristic synchronization patterns of brain regions that are "progressive and earlier" or "abrupt but delayed" account for previously reported behavioral responses of gradual and abrupt emergence from the unconscious state. The characteristic network synchronization processes observed at different scales provide new insights into how regional brain functions are reconstituted during progressive and abrupt emergence from the unconscious state. This theoretical approach also offers a principled explanation of how the brain reconstitutes consciousness and cognitive functions after physiologic (sleep), pharmacologic (anesthesia), and pathologic (coma) perturbations.

Experimental investigation of the mechanical properties of brain simulants used for cranial gunshot simulation.

PubMed

Lazarjan, Milad Soltanipour; Geoghegan, Patrick Henry; Jermy, Mark Christopher; Taylor, Michael

2014-06-01

The mechanical properties of the human brain at high strain rate were investigated to analyse the mechanisms that cause backspatter when a cranial gunshot wound occurs. Different concentrations of gelatine and a new material (M1) developed in this work were tested and compared to bovine brain samples. Kinetic energy absorption and expansion rate of the samples caused by the impact of a bullet from .22 air rifle (AR) (average velocity (uav) of 290m/s) and .22 long rifle (LR) (average velocity (uav) of 330m/s) were analysed using a high speed camera (24,000fps). The AR projectile had, in the region of interest, an average kinetic energy (Ek) of 42±1.3J. On average, the bovine brain absorbed 50±5% of Ek, and the simulants 46-58±5%. The Ek of the .22 LR was 141±3.7J. The bovine brain absorbed 27% of the .22LR Ek and the simulants 15-29%. The expansion of the sample, after penetration, was measured. The bovine brain experienced significant plastic deformation whereas the gelatine solution exhibited a principally elastic response. The permanent damage patterns in the M1 material were much closer to those in brain tissue, than were the damage patterns in the gelatine. The results provide a first step to developing a realistic experimental simulant for the human brain which can produce the same blood backspatter patterns as a human brain during a cranial gunshot. These results can also be used to improve the 3D models of human heads used in car crash and blast trauma injury research. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The functional neuroanatomy of maternal love: mother's response to infant's attachment behaviors.

PubMed

Noriuchi, Madoka; Kikuchi, Yoshiaki; Senoo, Atsushi

2008-02-15

Maternal love, which may be the core of maternal behavior, is essential for the mother-infant attachment relationship and is important for the infant's development and mental health. However, little has been known about these neural mechanisms in human mothers. We examined patterns of maternal brain activation in response to infant cues using video clips. We performed functional magnetic resonance imaging (fMRI) measurements while 13 mothers viewed video clips, with no sound, of their own infant and other infants of approximately 16 months of age who demonstrated two different attachment behaviors (smiling at the infant's mother and crying for her). We found that a limited number of the mother's brain areas were specifically involved in recognition of the mother's own infant, namely orbitofrontal cortex (OFC), periaqueductal gray, anterior insula, and dorsal and ventrolateral parts of putamen. Additionally, we found the strong and specific mother's brain response for the mother's own infant's distress. The differential neural activation pattern was found in the dorsal region of OFC, caudate nucleus, right inferior frontal gyrus, dorsomedial prefrontal cortex (PFC), anterior cingulate, posterior cingulate, thalamus, substantia nigra, posterior superior temporal sulcus, and PFC. Our results showed the highly elaborate neural mechanism mediating maternal love and diverse and complex maternal behaviors for vigilant protectiveness.

The change of the brain activation patterns as children learn algebra equation solving

NASA Astrophysics Data System (ADS)

Qin, Yulin; Carter, Cameron S.; Silk, Eli M.; Stenger, V. Andrew; Fissell, Kate; Goode, Adam; Anderson, John R.

2004-04-01

In a brain imaging study of children learning algebra, it is shown that the same regions are active in children solving equations as are active in experienced adults solving equations. As with adults, practice in symbol manipulation produces a reduced activation in prefrontal cortex area. However, unlike adults, practice seems also to produce a decrease in a parietal area that is holding an image of the equation. This finding suggests that adolescents' brain responses are more plastic and change more with practice. These results are integrated in a cognitive model that predicts both the behavioral and brain imaging results.

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.

Optimal design of a bank of spatio-temporal filters for EEG signal classification.

PubMed

Higashi, Hiroshi; Tanaka, Toshihisa

2011-01-01

The spatial weights for electrodes called common spatial pattern (CSP) are known to be effective in EEG signal classification for motor imagery based brain computer interfaces (MI-BCI). To achieve accurate classification in CSP, the frequency filter should be properly designed. To this end, several methods for designing the filter have been proposed. However, the existing methods cannot consider plural brain activities described with different frequency bands and different spatial patterns such as activities of mu and beta rhythms. In order to efficiently extract these brain activities, we propose a method to design plural filters and spatial weights which extract desired brain activity. The proposed method designs finite impulse response (FIR) filters and the associated spatial weights by optimization of an objective function which is a natural extension of CSP. Moreover, we show by a classification experiment that the bank of FIR filters which are designed by introducing an orthogonality into the objective function can extract good discriminative features. Moreover, the experiment result suggests that the proposed method can automatically detect and extract brain activities related to motor imagery.

Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities.

PubMed

Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2015-09-30

Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal-occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention.

Experiential, autonomic, and neural responses during threat anticipation vary as a function of threat intensity and neuroticism.

PubMed

Drabant, Emily M; Kuo, Janice R; Ramel, Wiveka; Blechert, Jens; Edge, Michael D; Cooper, Jeff R; Goldin, Philippe R; Hariri, Ahmad R; Gross, James J

2011-03-01

Anticipatory emotional responses play a crucial role in preparing individuals for impending challenges. They do this by triggering a coordinated set of changes in behavioral, autonomic, and neural response systems. In the present study, we examined the biobehavioral impact of varying levels of anticipatory anxiety, using a shock anticipation task in which unpredictable electric shocks were threatened and delivered to the wrist at variable intervals and intensities (safe, medium, strong). This permitted investigation of a dynamic range of anticipatory anxiety responses. In two studies, 95 and 51 healthy female participants, respectively, underwent this shock anticipation task while providing continuous ratings of anxiety experience and electrodermal responding (Study 1) and during fMRI BOLD neuroimaging (Study 2). Results indicated a step-wise pattern of responding in anxiety experience and electrodermal responses. Several brain regions showed robust responses to shock anticipation relative to safe trials, including the hypothalamus, periaqueductal gray, caudate, precentral gyrus, thalamus, insula, ventrolateral PFC, dorsomedial PFC, and ACC. A subset of these regions demonstrated a linear pattern of increased responding from safe to medium to strong trials, including the bilateral insula, ACC, and inferior frontal gyrus. These responses were modulated by individual differences in neuroticism, such that those high in neuroticism showed exaggerated anxiety experience across the entire task, and reduced brain activation from medium to strong trials in a subset of brain regions. These findings suggest that individual differences in neuroticism may influence sensitivity to anticipatory threat and provide new insights into the mechanism through which neuroticism may confer risk for developing anxiety disorders via dysregulated anticipatory responses. Copyright © 2010 Elsevier Inc. All rights reserved.

Neurological consequences of systemic inflammation in the premature neonate.

PubMed

Patra, Aparna; Huang, Hong; Bauer, John A; Giannone, Peter J

2017-06-01

Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

A 3-dimensional DTI MRI-based model of GBM growth and response to radiation therapy.

PubMed

Hathout, Leith; Patel, Vishal; Wen, Patrick

2016-09-01

Glioblastoma (GBM) is both the most common and the most aggressive intra-axial brain tumor, with a notoriously poor prognosis. To improve this prognosis, it is necessary to understand the dynamics of GBM growth, response to treatment and recurrence. The present study presents a mathematical diffusion-proliferation model of GBM growth and response to radiation therapy based on diffusion tensor (DTI) MRI imaging. This represents an important advance because it allows 3-dimensional tumor modeling in the anatomical context of the brain. Specifically, tumor infiltration is guided by the direction of the white matter tracts along which glioma cells infiltrate. This provides the potential to model different tumor growth patterns based on location within the brain, and to simulate the tumor's response to different radiation therapy regimens. Tumor infiltration across the corpus callosum is simulated in biologically accurate time frames. The response to radiation therapy, including changes in cell density gradients and how these compare across different radiation fractionation protocols, can be rendered. Also, the model can estimate the amount of subthreshold tumor which has extended beyond the visible MR imaging margins. When combined with the ability of being able to estimate the biological parameters of invasiveness and proliferation of a particular GBM from serial MRI scans, it is shown that the model has potential to simulate realistic tumor growth, response and recurrence patterns in individual patients. To the best of our knowledge, this is the first presentation of a DTI-based GBM growth and radiation therapy treatment model.

Reproducibility and discriminability of brain patterns of semantic categories enhanced by congruent audiovisual stimuli.

PubMed

Li, Yuanqing; Wang, Guangyi; Long, Jinyi; Yu, Zhuliang; Huang, Biao; Li, Xiaojian; Yu, Tianyou; Liang, Changhong; Li, Zheng; Sun, Pei

2011-01-01

One of the central questions in cognitive neuroscience is the precise neural representation, or brain pattern, associated with a semantic category. In this study, we explored the influence of audiovisual stimuli on the brain patterns of concepts or semantic categories through a functional magnetic resonance imaging (fMRI) experiment. We used a pattern search method to extract brain patterns corresponding to two semantic categories: "old people" and "young people." These brain patterns were elicited by semantically congruent audiovisual, semantically incongruent audiovisual, unimodal visual, and unimodal auditory stimuli belonging to the two semantic categories. We calculated the reproducibility index, which measures the similarity of the patterns within the same category. We also decoded the semantic categories from these brain patterns. The decoding accuracy reflects the discriminability of the brain patterns between two categories. The results showed that both the reproducibility index of brain patterns and the decoding accuracy were significantly higher for semantically congruent audiovisual stimuli than for unimodal visual and unimodal auditory stimuli, while the semantically incongruent stimuli did not elicit brain patterns with significantly higher reproducibility index or decoding accuracy. Thus, the semantically congruent audiovisual stimuli enhanced the within-class reproducibility of brain patterns and the between-class discriminability of brain patterns, and facilitate neural representations of semantic categories or concepts. Furthermore, we analyzed the brain activity in superior temporal sulcus and middle temporal gyrus (STS/MTG). The strength of the fMRI signal and the reproducibility index were enhanced by the semantically congruent audiovisual stimuli. Our results support the use of the reproducibility index as a potential tool to supplement the fMRI signal amplitude for evaluating multimodal integration.

Reproducibility and Discriminability of Brain Patterns of Semantic Categories Enhanced by Congruent Audiovisual Stimuli

PubMed Central

Long, Jinyi; Yu, Zhuliang; Huang, Biao; Li, Xiaojian; Yu, Tianyou; Liang, Changhong; Li, Zheng; Sun, Pei

2011-01-01

One of the central questions in cognitive neuroscience is the precise neural representation, or brain pattern, associated with a semantic category. In this study, we explored the influence of audiovisual stimuli on the brain patterns of concepts or semantic categories through a functional magnetic resonance imaging (fMRI) experiment. We used a pattern search method to extract brain patterns corresponding to two semantic categories: “old people” and “young people.” These brain patterns were elicited by semantically congruent audiovisual, semantically incongruent audiovisual, unimodal visual, and unimodal auditory stimuli belonging to the two semantic categories. We calculated the reproducibility index, which measures the similarity of the patterns within the same category. We also decoded the semantic categories from these brain patterns. The decoding accuracy reflects the discriminability of the brain patterns between two categories. The results showed that both the reproducibility index of brain patterns and the decoding accuracy were significantly higher for semantically congruent audiovisual stimuli than for unimodal visual and unimodal auditory stimuli, while the semantically incongruent stimuli did not elicit brain patterns with significantly higher reproducibility index or decoding accuracy. Thus, the semantically congruent audiovisual stimuli enhanced the within-class reproducibility of brain patterns and the between-class discriminability of brain patterns, and facilitate neural representations of semantic categories or concepts. Furthermore, we analyzed the brain activity in superior temporal sulcus and middle temporal gyrus (STS/MTG). The strength of the fMRI signal and the reproducibility index were enhanced by the semantically congruent audiovisual stimuli. Our results support the use of the reproducibility index as a potential tool to supplement the fMRI signal amplitude for evaluating multimodal integration. PMID:21750692

Brain correlates of discourse processing: An fMRI investigation of irony and conventional metaphor comprehension

PubMed Central

Eviatar, Zohar; Just, Marcel Adam

2006-01-01

Higher levels of discourse processing evoke patterns of cognition and brain activation that extend beyond the literal comprehension of sentences. We used fMRI to examine brain activation patterns while 16 healthy participants read brief three-sentence stories that concluded with either a literal, metaphoric, or ironic sentence. The fMRI images acquired during the reading of the critical sentence revealed a selective response of the brain to the two types of nonliteral utterances. Metaphoric utterances resulted in significantly higher levels of activation in the left inferior frontal gyrus and in bilateral inferior temporal cortex than the literal and ironic utterances. Ironic statements resulted in significantly higher activation levels than literal statements in the right superior and middle temporal gyri, with metaphoric statements resulting in intermediate levels in these regions. The findings show differential hemispheric sensitivity to these aspects of figurative language, and are relevant to models of the functional cortical architecture of language processing in connected discourse. PMID:16806316

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

Anxiety type modulates immediate versus delayed engagement of attention-related brain regions.

PubMed

Spielberg, Jeffrey M; De Leon, Angeline A; Bredemeier, Keith; Heller, Wendy; Engels, Anna S; Warren, Stacie L; Crocker, Laura D; Sutton, Bradley P; Miller, Gregory A

2013-09-01

Background Habituation of the fear response, critical for the treatment of anxiety, is inconsistently observed during exposure to threatening stimuli. One potential explanation for this inconsistency is differential attentional engagement with negatively valenced stimuli as a function of anxiety type. Methods The present study tested this hypothesis by examining patterns of neural habituation associated with anxious arousal, characterized by panic symptoms and immediate engagement with negatively valenced stimuli, versus anxious apprehension, characterized by engagement in worry to distract from negatively valenced stimuli. Results As predicted, the two anxiety types evidenced distinct patterns of attentional engagement. Anxious arousal was associated with immediate activation in attention-related brain regions that habituated over time, whereas anxious apprehension was associated with delayed activation in attention-related brain regions that occurred only after habituation in a worry-related brain region. Conclusions Results further elucidate mechanisms involved in attention to negatively valenced stimuli and indicate that anxiety is a heterogeneous construct with regard to attention to such stimuli.

Anxiety type modulates immediate versus delayed engagement of attention-related brain regions

PubMed Central

Spielberg, Jeffrey M; De Leon, Angeline A; Bredemeier, Keith; Heller, Wendy; Engels, Anna S; Warren, Stacie L; Crocker, Laura D; Sutton, Bradley P; Miller, Gregory A

2013-01-01

Background Habituation of the fear response, critical for the treatment of anxiety, is inconsistently observed during exposure to threatening stimuli. One potential explanation for this inconsistency is differential attentional engagement with negatively valenced stimuli as a function of anxiety type. Methods The present study tested this hypothesis by examining patterns of neural habituation associated with anxious arousal, characterized by panic symptoms and immediate engagement with negatively valenced stimuli, versus anxious apprehension, characterized by engagement in worry to distract from negatively valenced stimuli. Results As predicted, the two anxiety types evidenced distinct patterns of attentional engagement. Anxious arousal was associated with immediate activation in attention-related brain regions that habituated over time, whereas anxious apprehension was associated with delayed activation in attention-related brain regions that occurred only after habituation in a worry-related brain region. Conclusions Results further elucidate mechanisms involved in attention to negatively valenced stimuli and indicate that anxiety is a heterogeneous construct with regard to attention to such stimuli. PMID:24392275

Brain activation-based sexual orientation in female-to-male transsexuals.

PubMed

Kim, T-H; Kim, G-W; Kim, S-K; Jeong, G-W

2016-01-01

This study was performed to identify the sexual orientation in association with brain activation pattern in response to visual erotic stimuli in female-to-male (FtM) transsexuals by using functional magnetic resonance imaging (fMRI). Eleven FtM transsexuals who have had sex-reassignment surgery to alter their natal bodies with the gender-identity disorder were participated. Brain activation for sexual orientation was induced by visual stimuli with female and male erotic nude pictures compared with emotionally-neutral pictures. During viewing the erotic female pictures, the brain areas dominantly activated consist of the superior frontal gyrus, supplementary motor area, anterior/median cingulate gyri and hypothalamus, whereas during viewing male pictures, the brain areas with predominant activities were the middle frontal gyrus, precentral gyrus, middle temporal gyrus, fusiform gyrus, angular gyrus, precuneus, superior/middle occipital gyri, cerebellar cortex and vermis. These findings demonstrate that the brain activation patterns induced by viewing male or female erotic pictures show some correlation to the sexual orientation opposite to the genetic sex in FtM transsexuals. This study would be helpful to understand the neural mechanism associated with visual sexual arousal in patients with gender disorder.

Attention to affective pictures in closed head injury: event-related brain potentials and cardiac responses.

PubMed

Solbakk, Anne-Kristin; Reinvang, Ivar; Svebak, Sven; Nielsen, Christopher S; Sundet, Kjetil

2005-02-01

We examined whether closed head injury patients show altered patterns of selective attention to stimulus categories that naturally evoke differential responses in healthy people. Self-reported rating and electrophysiological (event-related potentials [ERPs], heart rate [HR]) responses to affective pictures were studied in patients with mild head injury (n = 20; CT/MRI negative), in patients with predominantly frontal brain lesions (n = 12; CT/MRI confirmed), and in healthy controls (n = 20). Affective valence similarly modulated HR and ERP responses in all groups, but group differences occurred that were independent of picture valence. The attenuation of P3-slow wave amplitudes in the mild head injury group indicates a reduction in the engagement of attentional resources to the task. In contrast, the general enhancement of ERP amplitudes at occipital sites in the group with primarily frontal brain injury may reflect disinhibition of input at sensory receptive areas, possibly due to a deficit in top-down modulation performed by anterior control systems.

Deep brain stimulation changes basal ganglia output nuclei firing pattern in the dystonic hamster.

PubMed

Leblois, Arthur; Reese, René; Labarre, David; Hamann, Melanie; Richter, Angelika; Boraud, Thomas; Meissner, Wassilios G

2010-05-01

Dystonia is a heterogeneous syndrome of movement disorders characterized by involuntary muscle contractions leading to abnormal movements and postures. While medical treatment is often ineffective, deep brain stimulation (DBS) of the internal pallidum improves dystonia. Here, we studied the impact of DBS in the entopeduncular nucleus (EP), the rodent equivalent of the human globus pallidus internus, on basal ganglia output in the dt(sz)-hamster, a well-characterized model of dystonia by extracellular recordings. Previous work has shown that EP-DBS improves dystonic symptoms in dt(sz)-hamsters. We report that EP-DBS changes firing pattern in the EP, most neurons switching to a less regular firing pattern during DBS. In contrast, EP-DBS did not change the average firing rate of EP neurons. EP neurons display multiphasic responses to each stimulation impulse, likely underlying the disruption of their firing rhythm. Finally, neurons in the substantia nigra pars reticulata display similar responses to EP-DBS, supporting the idea that EP-DBS affects basal ganglia output activity through the activation of common afferent fibers. Copyright 2010 Elsevier Inc. All rights reserved.

Guiding the study of brain dynamics by using first-person data: Synchrony patterns correlate with ongoing conscious states during a simple visual task

PubMed Central

Lutz, Antoine; Lachaux, Jean-Philippe; Martinerie, Jacques; Varela, Francisco J.

2002-01-01

Even during well-calibrated cognitive tasks, successive brain responses to repeated identical stimulations are highly variable. The source of this variability is believed to reside mainly in fluctuations of the subject's cognitive “context” defined by his/her attentive state, spontaneous thought process, strategy to carry out the task, and so on … As these factors are hard to manipulate precisely, they are usually not controlled, and the variability is discarded by averaging techniques. We combined first-person data and the analysis of neural processes to reduce such noise. We presented the subjects with a three-dimensional illusion and recorded their electrical brain activity and their own report about their cognitive context. Trials were clustered according to these first-person data, and separate dynamical analyses were conducted for each cluster. We found that (i) characteristic patterns of endogenous synchrony appeared in frontal electrodes before stimulation. These patterns depended on the degree of preparation and the immediacy of perception as verbally reported. (ii) These patterns were stable for several recordings. (iii) Preparatory states modulate both the behavioral performance and the evoked and induced synchronous patterns that follow. (iv) These results indicated that first-person data can be used to detect and interpret neural processes. PMID:11805299

Pattern of brain activation during social cognitive tasks is related to social competence in siblings discordant for schizophrenia.

PubMed

Villarreal, Mirta F; Drucaroff, Lucas J; Goldschmidt, Micaela G; de Achával, Delfina; Costanzo, Elsa Y; Castro, Mariana N; Ladrón-de-Guevara, M Soledad; Busatto Filho, Geraldo; Nemeroff, Charles B; Guinjoan, Salvador M

2014-09-01

Measures of social competence are closely related to actual community functioning in patients with schizophrenia. However, the neurobiological mechanisms underlying competence in schizophrenia are not fully understood. We hypothesized that social deficits in schizophrenia are explained, at least in part, by abnormally lateralized patterns of brain activation in response to tasks engaging social cognition, as compared to healthy individuals. We predicted such patterns would be partly heritable, and therefore affected in patients' nonpsychotic siblings as well. We used a functional magnetic resonance image paradigm to characterize brain activation induced by theory of mind tasks, and two tests of social competence, the Test of Adaptive Behavior in Schizophrenia (TABS), and the Social Skills Performance Assessment (SSPA) in siblings discordant for schizophrenia and comparable healthy controls (n = 14 per group). Healthy individuals showed the strongest correlation between social competence and activation of right hemisphere structures involved in social cognitive processing, whereas in patients, the correlation pattern was lateralized to left hemisphere areas. Unaffected siblings of patients exhibited a pattern intermediate between the other groups. These results support the hypothesis that schizophrenia may be characterized by an abnormal functioning of nondominant hemisphere structures involved in the processing of socially salient information. Copyright © 2014 Elsevier Ltd. All rights reserved.

fMRI evidence of compensatory mechanisms in older adults at genetic risk for Alzheimer disease

PubMed Central

Bondi, Mark W.; Houston, Wes S.; Eyler, Lisa T.; Brown, Gregory G.

2006-01-01

Objective To determine whether APOE genotype influences brain response and whether nonverbal stimuli generate findings comparable with those of previous studies that used verbal stimuli. The relationship between APOE genotype and blood oxygenation level dependent (BOLD) brain response was examined during a picture-encoding task in nondemented older adults. Methods Twenty nondemented participants with normal episodic memory function were divided into two groups based on the presence (n = 10) or absence (n = 10) of the APOE ε4 allele. Picture learning was completed during functional MRI in a blocked design alternating between experimental (novel pictures) and control (repeated picture) conditions. Results Nondemented older adults with an APOE ε4 allele showed greater magnitude and extent of BOLD brain response during learning of new pictures relative to their matched ε3 counterparts. Different patterns and directions of association between hippocampal activity and learning and memory performance were also demonstrated. Conclusions The results suggest that brain response differences are not due to poorer general memory abilities, differential atrophy, or brain response during control conditions, but instead appear to be directly influenced by APOE genotype. Results are consistent with a compensatory hypothesis wherein older adults at genetic risk for Alzheimer disease by virtue of the APOE ε4 allele appear to require additional cognitive effort to achieve comparable performance levels on tests of episodic memory encoding. PMID:15699382

Effect of Frustration on Brain Activation Pattern in Subjects with Different Temperament

PubMed Central

Bierzynska, Maria; Bielecki, Maksymilian; Marchewka, Artur; Debowska, Weronika; Duszyk, Anna; Zajkowski, Wojciech; Falkiewicz, Marcel; Nowicka, Anna; Strelau, Jan; Kossut, Malgorzata

2016-01-01

In spite of the prevalence of frustration in everyday life, very few neuroimaging studies were focused on this emotional state. In the current study we aimed to examine effects of frustration on brain activity while performing a well-learned task in participants with low and high tolerance for arousal. Prior to the functional magnetic resonance imaging session, the subjects underwent 2 weeks of Braille reading training. Frustration induction was obtained by using a novel highly difficult tactile task based on discrimination of Braille-like raised dots patterns and negative feedback. Effectiveness of this procedure has been confirmed in a pilot study using galvanic skin response and questionnaires. Brain activation pattern during tactile discrimination task before and after frustration were compared directly. Results revealed changes in brain activity in structures mostly reported in acute stress studies: striatum, cingulate cortex, insula, middle frontal gyrus and precuneus and in structures engaged in tactile Braille discrimination: SI and SII. Temperament type affected activation pattern. Subjects with low tolerance for arousal showed higher activation in the posterior cingulate gyrus, precuneus, and inferior parietal lobule than high reactivity group. Even though performance in the discrimination trials following frustration was unaltered, we observed increased activity of primary and secondary somatosensory cortex processing the tactile information. We interpret this effect as an indicator of additional involvement required to counteract the effects of frustration. PMID:26793136

Effect of Frustration on Brain Activation Pattern in Subjects with Different Temperament.

PubMed

Bierzynska, Maria; Bielecki, Maksymilian; Marchewka, Artur; Debowska, Weronika; Duszyk, Anna; Zajkowski, Wojciech; Falkiewicz, Marcel; Nowicka, Anna; Strelau, Jan; Kossut, Malgorzata

2015-01-01

In spite of the prevalence of frustration in everyday life, very few neuroimaging studies were focused on this emotional state. In the current study we aimed to examine effects of frustration on brain activity while performing a well-learned task in participants with low and high tolerance for arousal. Prior to the functional magnetic resonance imaging session, the subjects underwent 2 weeks of Braille reading training. Frustration induction was obtained by using a novel highly difficult tactile task based on discrimination of Braille-like raised dots patterns and negative feedback. Effectiveness of this procedure has been confirmed in a pilot study using galvanic skin response and questionnaires. Brain activation pattern during tactile discrimination task before and after frustration were compared directly. Results revealed changes in brain activity in structures mostly reported in acute stress studies: striatum, cingulate cortex, insula, middle frontal gyrus and precuneus and in structures engaged in tactile Braille discrimination: SI and SII. Temperament type affected activation pattern. Subjects with low tolerance for arousal showed higher activation in the posterior cingulate gyrus, precuneus, and inferior parietal lobule than high reactivity group. Even though performance in the discrimination trials following frustration was unaltered, we observed increased activity of primary and secondary somatosensory cortex processing the tactile information. We interpret this effect as an indicator of additional involvement required to counteract the effects of frustration.

Selective attention determines emotional responses to novel visual stimuli.

PubMed

Raymond, Jane E; Fenske, Mark J; Tavassoli, Nader T

2003-11-01

Distinct complex brain systems support selective attention and emotion, but connections between them suggest that human behavior should reflect reciprocal interactions of these systems. Although there is ample evidence that emotional stimuli modulate attentional processes, it is not known whether attention influences emotional behavior. Here we show that evaluation of the emotional tone (cheery/dreary) of complex but meaningless visual patterns can be modulated by the prior attentional state (attending vs. ignoring) used to process each pattern in a visual selection task. Previously ignored patterns were evaluated more negatively than either previously attended or novel patterns. Furthermore, this emotional devaluation of distracting stimuli was robust across different emotional contexts and response scales. Finding that negative affective responses are specifically generated for ignored stimuli points to a new functional role for attention and elaborates the link between attention and emotion. This finding also casts doubt on the conventional marketing wisdom that any exposure is good exposure.

Brain connectivity study of joint attention using frequency-domain optical imaging technique

NASA Astrophysics Data System (ADS)

Chaudhary, Ujwal; Zhu, Banghe; Godavarty, Anuradha

2010-02-01

Autism is a socio-communication brain development disorder. It is marked by degeneration in the ability to respond to joint attention skill task, from as early as 12 to 18 months of age. This trait is used to distinguish autistic from nonautistic populations. In this study, diffuse optical imaging is being used to study brain connectivity for the first time in response to joint attention experience in normal adults. The prefrontal region of the brain was non-invasively imaged using a frequency-domain based optical imager. The imaging studies were performed on 11 normal right-handed adults and optical measurements were acquired in response to joint-attention based video clips. While the intensity-based optical data provides information about the hemodynamic response of the underlying neural process, the time-dependent phase-based optical data has the potential to explicate the directional information on the activation of the brain. Thus brain connectivity studies are performed by computing covariance/correlations between spatial units using this frequency-domain based optical measurements. The preliminary results indicate that the extent of synchrony and directional variation in the pattern of activation varies in the left and right frontal cortex. The results have significant implication for research in neural pathways associated with autism that can be mapped using diffuse optical imaging tools in the future.

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.

Focused microwave irradiation-assisted immunohistochemistry to study effects of ketamine on phospho-ERK expression in the mouse brain.

PubMed

Fernandes, Alda; Li, Yu-Wen

2017-09-01

Ketamine produces rapid and long-lasting antidepressant effects in depressive patients. Preclinical studies demonstrate that ketamine stimulates AMPA receptor transmission and activates BDNF/TrkB-Akt/ERK-mTOR signaling cascades, leading to a sustained increase in synaptic protein synthesis and strengthening of synaptic plasticity, a potential mechanism underlying the antidepressant effects. The purpose of this study was to develop an immunohistochemistry (IHC) assay to map the distribution of extracellular signal-regulated kinase (ERK) phosphorylation in the mouse brain in response to systemic ketamine treatment. We established a focused microwave irradiation-assisted IHC assay to detect phosphorylated (phospho) proteins including phospho-ERK, phospho- cAMP-response- element-binding protein (CREB), phospho- glutamate receptor 1 (GluR1) and phospho- calcium/calmodulin-dependent protein kinase II (CaMKII) with greater sensitivity and reproducibility in comparison to conventional IHC methods. A single dose of ketamine produced a robust, dose- and time-dependent increase in phospho-ERK immunoreactive (phospho-ERK-ir) neurons in the medial prefrontal cortex (mPFC) and the central nucleus of the amygdala. Phospho-ERK-ir neurons in the mPFC were primarily located in the prelimbic and anterior cingulate subregions with the morphology resembling pyramidal neurons. An increase in phospho-ERK-ir was also observed in the brainstem dorsal raphe nucleus and locus coeruleus. The NMDA GluN2B subtype receptor antagonist Ro 25-6981 increased phospho-ERK expression in the brain in a similar pattern as ketamine. In summary, we have established a sensitive and reliable focused microwave irradiation-assisted IHC assay, and defined the activation pattern of ERK, in response to systemic ketamine and Ro 25-6981 treatment, in brain regions that are potentially responsible for mediating the antidepressant effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Affective communication in rodents: ultrasonic vocalizations as a tool for research on emotion and motivation.

PubMed

Wöhr, Markus; Schwarting, Rainer K W

2013-10-01

Mice and rats emit and perceive calls in the ultrasonic range, i.e., above the human hearing threshold of about 20 kHz: so-called ultrasonic vocalizations (USV). Juvenile and adult rats emit 22-kHz USV in aversive situations, such as predator exposure and fighting or during drug withdrawal, whereas 50-kHz USV occur in appetitive situations, such as rough-and-tumble play and mating or in response to drugs of abuse, e.g., amphetamine. Aversive 22-kHz USV and appetitive 50-kHz USV serve distinct communicative functions. Whereas 22-kHz USV induce freezing behavior in the receiver, 50-kHz USV lead to social approach behavior. These opposite behavioral responses are paralleled by distinct patterns of brain activation. Freezing behavior in response to 22-kHz USV is paralleled by increased neuronal activity in brain areas regulating fear and anxiety, such as the amygdala and periaqueductal gray, whereas social approach behavior elicited by 50-kHz USV is accompanied by reduced activity levels in the amygdala but enhanced activity in the nucleus accumbens, a brain area implicated in reward processing. These opposing behavioral responses, together with distinct patterns of brain activation, particularly the bidirectional tonic activation or deactivation of the amygdala elicited by 22-kHz and 50-kHz USV, respectively, concur with a wealth of behavioral and neuroimaging studies in humans involving emotionally salient stimuli, such as fearful and happy facial expressions. Affective ultrasonic communication therefore offers a translational tool for studying the neurobiology underlying socio-affective communication. This is particularly relevant for rodent models of neurodevelopmental disorders characterized by social and communication deficits, such as autism and schizophrenia.

fMRI response to spatial working memory in adolescents with comorbid marijuana and alcohol use disorders☆

PubMed Central

Schweinsburg, Alecia D.; Schweinsburg, Brian C.; Cheung, Erick H.; Brown, Gregory G.; Brown, Sandra A.; Tapert, Susan F.

2008-01-01

Alcohol and marijuana use are prevalent in adolescence, yet the neural impact of concomitant use remains unclear. We previously demonstrated functional magnetic resonance imaging (fMRI) response to spatial working memory (SWM) among teens with alcohol use disorders (AUD) compared to controls, and predicted that adolescents with marijuana and alcohol use disorders would show additional abnormalities. Participants were three groups of 15−17-year-olds: 19 non-abusing controls, 15 AUD teens with limited exposure to drugs, and 15 teens with comorbid marijuana and alcohol use disorders (MAUD) and minimal other drug experience. After >2 days’ abstinence, participants performed a SWM task during fMRI acquisition. fMRI brain response patterns differed between groups, despite similar performance on the task. MAUD youths showed less activation in inferior frontal and temporal regions than controls, and more response in other prefrontal regions. Compared to AUD teens, MAUD youths also showed less inferior frontal and temporal activation, but more medial frontal response. Overall, MAUD youths showed different brain response abnormalities than teens with AUD alone, despite relatively short histories of substance involvement. This pattern could suggest compensation for marijuana-related attention and working memory deficits. However, relatively recent use and premorbid features may influence results, and should be examined in future studies. PMID:16002029

Engaged listeners: shared neural processing of powerful political speeches

PubMed Central

Häcker, Frank E. K.; Honey, Christopher J.; Hasson, Uri

2015-01-01

Powerful speeches can captivate audiences, whereas weaker speeches fail to engage their listeners. What is happening in the brains of a captivated audience? Here, we assess audience-wide functional brain dynamics during listening to speeches of varying rhetorical quality. The speeches were given by German politicians and evaluated as rhetorically powerful or weak. Listening to each of the speeches induced similar neural response time courses, as measured by inter-subject correlation analysis, in widespread brain regions involved in spoken language processing. Crucially, alignment of the time course across listeners was stronger for rhetorically powerful speeches, especially for bilateral regions of the superior temporal gyri and medial prefrontal cortex. Thus, during powerful speeches, listeners as a group are more coupled to each other, suggesting that powerful speeches are more potent in taking control of the listeners’ brain responses. Weaker speeches were processed more heterogeneously, although they still prompted substantially correlated responses. These patterns of coupled neural responses bear resemblance to metaphors of resonance, which are often invoked in discussions of speech impact, and contribute to the literature on auditory attention under natural circumstances. Overall, this approach opens up possibilities for research on the neural mechanisms mediating the reception of entertaining or persuasive messages. PMID:25653012

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

PubMed

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

2016-12-15

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

Brain c-fos expression patterns induced by emotional stressors differing in nature and intensity.

PubMed

Úbeda-Contreras, Jesús; Marín-Blasco, Ignacio; Nadal, Roser; Armario, Antonio

2018-06-01

Regardless of its particular nature, emotional stressors appear to elicit a widespread and roughly similar brain activation pattern as evaluated by c-fos expression. However, their behavioral and physiological consequences may strongly differ. Here we addressed in adult male rats the contribution of the intensity and the particular nature of stressors by comparing, in a set of brain areas, the number of c-fos expressing neurons in response to open-field, cat odor or immobilization on boards (IMO). These are qualitatively different stressors that are known to differ in terms of intensity, as evaluated by biological markers. In the present study, plasma levels of the adrenocorticotropic hormone (ACTH) demonstrated that intensity increases in the following order: open-field, cat odor and IMO. Four different c-fos activation patterns emerged among all areas studied: (i) positive relationship with intensity (posterior-dorsal medial amygdala, dorsomedial hypothalamus, lateral septum ventral and paraventricular nucleus of the hypothalamus), (ii) negative relationship with intensity (cingulate cortex 1, posterior insular cortex, dorsal striatum, nucleus accumbens and some subdivisions of the hippocampal formation); (iii) activation not dependent on the intensity of the stressor (prelimbic and infralimbic cortex and lateral and basolateral amygdala); and (iv) activation specifically associated with cat odor (ventromedial amygdala and ventromedial hypothalamus). Histone 3 phosphorylation at serine 10, another neuronal activation marker, corroborated c-fos results. Summarizing, deepest analysis of the brain activation pattern elicit by emotional stressor indicated that, in spite of activating similar areas, each stressor possess their own brain activation signature, mediated mainly by qualitative aspects but also by intensity.

Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria

PubMed Central

Das, Soumita; Owen, Katherine A.; Ly, Kim T.; Park, Daeho; Black, Steven G.; Wilson, Jeffrey M.; Sifri, Costi D.; Ravichandran, Kodi S.; Ernst, Peter B.; Casanova, James E.

2011-01-01

Bacterial recognition by host cells is essential for initiation of infection and the host response. Bacteria interact with host cells via multiple pattern recognition receptors that recognize microbial products or pathogen-associated molecular patterns. In response to this interaction, host cell signaling cascades are activated that lead to inflammatory responses and/or phagocytic clearance of attached bacteria. Brain angiogenesis inhibitor 1 (BAI1) is a receptor that recognizes apoptotic cells through its conserved type I thrombospondin repeats and triggers their engulfment through an ELMO1/Dock/Rac1 signaling module. Because thrombospondin repeats in other proteins have been shown to bind bacterial surface components, we hypothesized that BAI1 may also mediate the recognition and clearance of pathogenic bacteria. We found that preincubation of bacteria with recombinant soluble BAI1 ectodomain or knockdown of endogenous BAI1 in primary macrophages significantly reduced binding and internalization of the Gram-negative pathogen Salmonella typhimurium. Conversely, overexpression of BAI1 enhanced attachment and engulfment of Salmonella in macrophages and in heterologous nonphagocytic cells. Bacterial uptake is triggered by the BAI1-mediated activation of Rac through an ELMO/Dock-dependent mechanism, and inhibition of the BAI1/ELMO1 interaction prevents both Rac activation and bacterial uptake. Moreover, inhibition of ELMO1 or Rac function significantly impairs the proinflammatory response to infection. Finally, we show that BAI1 interacts with a variety of Gram-negative, but not Gram-positive, bacteria through recognition of their surface lipopolysaccharide. Together these findings identify BAI1 as a pattern recognition receptor that mediates nonopsonic phagocytosis of Gram-negative bacteria by macrophages and directly affects the host response to infection. PMID:21245295

Epigenetic dysregulation of the dopamine system in diet-induced obesity.

PubMed

Vucetic, Zivjena; Carlin, Jesse Lea; Totoki, Kathy; Reyes, Teresa M

2012-03-01

Chronic intake of high-fat (HF) diet is known to alter brain neurotransmitter systems that participate in the central regulation of food intake. Dopamine (DA) system changes in response to HF diet have been observed in the hypothalamus, important in the homeostatic control of food intake, as well as within the central reward circuitry [ventral tegmental area (VTA), nucleus accumbens (NAc), and pre-frontal cortex (PFC)], critical for coding the rewarding properties of palatable food and important in hedonically driven feeding behavior. Using a mouse model of diet-induced obesity (DIO), significant alterations in the expression of DA-related genes were documented in adult animals, and the general pattern of gene expression changes was opposite within the hypothalamus versus the reward circuitry (increased vs. decreased, respectively). Differential DNA methylation was identified within the promoter regions of tyrosine hydroxylase (TH) and dopamine transporter (DAT), and the pattern of this response was consistent with the pattern of gene expression. Behaviors consistent with increased hypothalamic DA and decreased reward circuitry DA were observed. These data identify differential DNA methylation as an epigenetic mechanism linking the chronic intake of HF diet with altered DA-related gene expression, and this response varies by brain region and DNA sequence. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Linear Representation of Emotions in Whole Persons by Combining Facial and Bodily Expressions in the Extrastriate Body Area

PubMed Central

Yang, Xiaoli; Xu, Junhai; Cao, Linjing; Li, Xianglin; Wang, Peiyuan; Wang, Bin; Liu, Baolin

2018-01-01

Our human brain can rapidly and effortlessly perceive a person’s emotional state by integrating the isolated emotional faces and bodies into a whole. Behavioral studies have suggested that the human brain encodes whole persons in a holistic rather than part-based manner. Neuroimaging studies have also shown that body-selective areas prefer whole persons to the sum of their parts. The body-selective areas played a crucial role in representing the relationships between emotions expressed by different parts. However, it remains unclear in which regions the perception of whole persons is represented by a combination of faces and bodies, and to what extent the combination can be influenced by the whole person’s emotions. In the present study, functional magnetic resonance imaging data were collected when participants performed an emotion distinction task. Multi-voxel pattern analysis was conducted to examine how the whole person-evoked responses were associated with the face- and body-evoked responses in several specific brain areas. We found that in the extrastriate body area (EBA), the whole person patterns were most closely correlated with weighted sums of face and body patterns, using different weights for happy expressions but equal weights for angry and fearful ones. These results were unique for the EBA. Our findings tentatively support the idea that the whole person patterns are represented in a part-based manner in the EBA, and modulated by emotions. These data will further our understanding of the neural mechanism underlying perceiving emotional persons. PMID:29375348

Multitasking: Effects of processing multiple auditory feature patterns

PubMed Central

Miller, Tova; Chen, Sufen; Lee, Wei Wei; Sussman, Elyse S.

2016-01-01

ERPs and behavioral responses were measured to assess how task-irrelevant sounds interact with task processing demands and affect the ability to monitor and track multiple sound events. Participants listened to four-tone sequential frequency patterns, and responded to frequency pattern deviants (reversals of the pattern). Irrelevant tone feature patterns (duration and intensity) and respective pattern deviants were presented together with frequency patterns and frequency pattern deviants in separate conditions. Responses to task-relevant and task-irrelevant feature pattern deviants were used to test processing demands for irrelevant sound input. Behavioral performance was significantly better when there were no distracting feature patterns. Errors primarily occurred in response to the to-be-ignored feature pattern deviants. Task-irrelevant elicitation of ERP components was consistent with the error analysis, indicating a level of processing for the irrelevant features. Task-relevant elicitation of ERP components was consistent with behavioral performance, demonstrating a “cost” of performance when there were two feature patterns presented simultaneously. These results provide evidence that the brain tracked the irrelevant duration and intensity feature patterns, affecting behavioral performance. Overall, our results demonstrate that irrelevant informational streams are processed at a cost, which may be considered a type of multitasking that is an ongoing, automatic processing of taskirrelevant sensory events. PMID:25939456

Peptide vaccine immunotherapy biomarkers and response patterns in pediatric gliomas

PubMed Central

Müller, Sören; Agnihotri, Sameer; Shoger, Karsen E.; Myers, Max I.; Chaparala, Srilakshmi; Villanueva, Clarence R.; Chattopadhyay, Ansuman; Butterfield, Lisa H.; Okada, Hideho; Pollack, Ian F.

2018-01-01

Low-grade gliomas (LGGs) are the most common brain tumor affecting children. We recently reported an early phase clinical trial of a peptide-based vaccine, which elicited consistent antigen-specific T cell responses in pediatric LGG patients. Additionally, we observed radiologic responses of stable disease (SD), partial response (PR), and near-complete/complete response (CR) following therapy. To identify biomarkers of clinical response in peripheral blood, we performed RNA sequencing on PBMC samples collected at multiple time points. Patients who showed CR demonstrated elevated levels of T cell activation markers, accompanied by a cytotoxic T cell response shortly after treatment initiation. At week 34, patients with CR demonstrated both IFN signaling and Poly-IC:LC adjuvant response patterns. Patients with PR demonstrated a unique, late monocyte response signature. Interestingly, HLA-V expression, before or during therapy, and an early monocytic hematopoietic response were strongly associated with SD. Finally, low IDO1 and PD-L1 expression before treatment and early elevated levels of T cell activation markers were associated with prolonged progression-free survival. Overall, our data support the presence of unique peripheral immune patterns in LGG patients associated with different radiographic responses to our peptide vaccine immunotherapy. Future clinical trials, including our ongoing phase II LGG vaccine immunotherapy, should monitor these response patterns. PMID:29618666

Reconstructing the spectrotemporal modulations of real-life sounds from fMRI response patterns

PubMed Central

Santoro, Roberta; Moerel, Michelle; De Martino, Federico; Valente, Giancarlo; Ugurbil, Kamil; Yacoub, Essa; Formisano, Elia

2017-01-01

Ethological views of brain functioning suggest that sound representations and computations in the auditory neural system are optimized finely to process and discriminate behaviorally relevant acoustic features and sounds (e.g., spectrotemporal modulations in the songs of zebra finches). Here, we show that modeling of neural sound representations in terms of frequency-specific spectrotemporal modulations enables accurate and specific reconstruction of real-life sounds from high-resolution functional magnetic resonance imaging (fMRI) response patterns in the human auditory cortex. Region-based analyses indicated that response patterns in separate portions of the auditory cortex are informative of distinctive sets of spectrotemporal modulations. Most relevantly, results revealed that in early auditory regions, and progressively more in surrounding regions, temporal modulations in a range relevant for speech analysis (∼2–4 Hz) were reconstructed more faithfully than other temporal modulations. In early auditory regions, this effect was frequency-dependent and only present for lower frequencies (<∼2 kHz), whereas for higher frequencies, reconstruction accuracy was higher for faster temporal modulations. Further analyses suggested that auditory cortical processing optimized for the fine-grained discrimination of speech and vocal sounds underlies this enhanced reconstruction accuracy. In sum, the present study introduces an approach to embed models of neural sound representations in the analysis of fMRI response patterns. Furthermore, it reveals that, in the human brain, even general purpose and fundamental neural processing mechanisms are shaped by the physical features of real-world stimuli that are most relevant for behavior (i.e., speech, voice). PMID:28420788

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain

PubMed Central

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain. PMID:23440889

Neuron-Enriched Gene Expression Patterns are Regionally Anti-Correlated with Oligodendrocyte-Enriched Patterns in the Adult Mouse and Human Brain.

PubMed

Tan, Powell Patrick Cheng; French, Leon; Pavlidis, Paul

2013-01-01

An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia to neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA) on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

Nitric Oxide in the Crustacean Brain: Regulation of Neurogenesis and Morphogenesis in the Developing Olfactory Pathway

PubMed Central

Benton, J.L.; Sandeman, D.C.; Beltz, B.S.

2009-01-01

Nitric oxide (NO) plays major roles during development and in adult organisms. We examined the temporal and spatial patterns of nitric oxide synthase (NOS) appearance in the embryonic lobster brain to localize sources of NO activity; potential NO targets were identified by defining the distribution of NO-induced cGMP. Staining patterns are compared with NOS and cyclic 3,5 guanosine monophosphate (cGMP) distribution in adult lobster brains. Manipulation of NO levels influences olfactory glomerular formation and stabilization, as well as levels of neurogenesis among the olfactory projection neurons. In the first 2 days following ablation of the lateral antennular flagella in juvenile lobsters, a wave of increased NOS immunoreactivity and a reduction in neurogenesis occur. These studies implicate nitric oxide as a developmental architect and also support a role for this molecule in the neural response to injury in the olfactory pathway. PMID:17948307

Optical mapping of the brain activity in children with Down's syndrome

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Lu, Fengmei

2018-02-01

Down's syndrome (DS) has been shown to be associated with many neurological complications, including cognitive deficits, seizures, early-onset dementia that resembles Alzheimer's disease, and neurological complications of systemic disorders. DS patients show to have poor performance in executive functions (EF) and fine motor skills. In this study, we examined the brain hemodynamic responses and brain activation patterns of DS children during the completion of EF tasks. Revealing its neural mechanism of DS is not only able to contribute to the early intervention of this children with DS, but also increase understanding of developmental cascades in childhood.

Neural correlates of inhibitory control in adult ADHD: Evidence from the Milwaukee longitudinal sample

PubMed Central

Mulligan, Richard C.; Knopik, Valerie S.; Sweet, Lawrence H.; Fischer, Mariellen; Seidenberg, Michael; Rao, Stephen M.

2011-01-01

Only a few studies have investigated the neural substrate of response inhibition in adult ADHD using Stop-Signal and Go/No-Go tasks. Inconsistencies and methodological limitations in the existing literature have resulted in limited conclusions regarding underlying pathophysiology. We examined the neural basis of response inhibition in a group of adults diagnosed with ADHD in childhood and who continue to meet criteria for ADHD while addressing limitations present in earlier studies. Adults with ADHD (n=12) and controls (n=12) were recruited from an ongoing longitudinal study and were matched for age, IQ, and education. Individuals with comorbid conditions were excluded. Functional MRI was used to identify and compare the brain activation patterns during correct trials of a response inhibition task (Go/No-Go). Our results showed that the control group recruited a more extensive network of brain regions than the ADHD group during correct inhibition trials. Adults with ADHD showed reduced brain activation in the right frontal eye field, pre-supplementary motor area, left precentral gyrus, and the inferior parietal lobe bilaterally. During successful inhibition of an inappropriate response, adults with ADHD display reduced activation in fronto-parietal networks previously implicated in working memory, goal-oriented attention, and response selection. This profile of brain activation may be specifically associated with ADHD in adulthood. PMID:21937201

Electrical brain activity and response to olanzapine in schizophrenia: a study with LORETA images of P300.

PubMed

Sumiyoshi, Tomiki; Higuchi, Yuko; Kawasaki, Yasuhiro; Matsui, Mie; Kato, Kanade; Yuuki, Hiromi; Arai, Hirofumi; Kurachi, Masayoshi

2006-09-30

The aim of this study was to evaluate the change in the distribution for the P300 generator, as demonstrated by Low Resolution Electromagnetic Tomography (LORETA) images, in patients with schizophrenia during treatment with olanzapine. Data were obtained from five right-handed patients treated with olanzapine for 6 months. Five right-handed normal volunteers also participated in the study. LORETA images of P300 in response to the odd-ball auditory discrimination task revealed a left dominant lateralized high current source density in the temporal lobes in all control subjects. Although this pattern of brain activation was not evident in patients at baseline, 6-month treatment with olanzapine recovered the left dominant pattern of the electrical density in the temporal regions, such as the Heschl gyrus, and improved performance on a test of verbal learning and memory. Scores of the Brief Psychiatric Rating Scale and the Global Assessment of Functioning Scale also improved during treatment. These results provide the first suggestion that enhancement of verbal memory and the functional status by treatment with some antipsychotic drugs may be associated with modulations of the anatomical configuration of electrical brain activity in patients with schizophrenia.

Alteration of brain activation patterns in nonallergic rhinitis patients using functional magnetic resonance imaging before and after treatment with intranasal azelastine.

PubMed

Bernstein, Jonathan A; Hastings, Lloyd; Boespflug, Erin L; Allendorfer, Jane B; Lamy, Martine; Eliassen, James C

2011-06-01

Although nonallergic rhinitis (NAR) patients tend to be more sensitive to chemical/olfactory stimuli, a suprathreshold olfactory response or the presence of specific olfactory receptor genes do not explain why their symptoms are triggered by such exposures. To investigate differential neurogenic responses to azelastine in NAR patients, using functional magnetic resonance imaging (fMRI) in response to specific olfactory triggers. A longitudinal study design on 12 subjects with a physician diagnosis of NAR previously demonstrated to be clinically responsive to intranasal azelastine (Astelin) was performed. Subjects underwent fMRI during exposure to unpleasant (hickory smoke) and pleasant (vanilla) odorants while off and then on azelastine for 2 weeks. The olfactory fMRI paradigm consisted of a visually triggered sniff every 21 seconds with synchronized delivery of a 4 second pulse of odorant. Each odorant was presented 18 times over 4-6-minute fMRI runs. Continuous fresh air was presented to wash out each odorant after presentation. Nonallergic rhinitis patients exhibited increased blood flow to several regions of the brain in response to both pleasant and unpleasant odorants, specifically in odor-sensitive regions, while off intranasal azelastine. Treatment with intranasal azelastine significantly attenuated blood flow to regions of the brain relevant to either olfactory sensation or sensory processing in response to these odorants compared with fresh air. The general reduction compared with increase in brain activation in NAR patients on versus off azelastine suggests that a possible effect of this medication may be reduction of brain responses to odorants. Copyright © 2011. Published by Elsevier Inc.

The evolving neurobiology of gut feelings.

PubMed

Mayer, E A; Naliboff, B; Munakata, J

2000-01-01

The bi-directional communication between limbic regions and the viscera play a central role in the generation and expression of emotional responses and associated emotional feelings. The response of different viscera to distinct, emotion-specific patterns of autonomic output is fed back to the brain, in particular to the cingulofrontal convergence region. Even though this process unfolds largely without conscious awareness, it plays an important role in emotional function and may influence rational decision making in the healthy individual. Alterations in this bi-directional process such as peripheral pathologies within the gut or alterations at the brain level may explain the close association between certain affective disorders and functional visceral syndromes.

Abstract representations of associated emotions in the human brain.

PubMed

Kim, Junsuk; Schultz, Johannes; Rohe, Tim; Wallraven, Christian; Lee, Seong-Whan; Bülthoff, Heinrich H

2015-04-08

Emotions can be aroused by various kinds of stimulus modalities. Recent neuroimaging studies indicate that several brain regions represent emotions at an abstract level, i.e., independently from the sensory cues from which they are perceived (e.g., face, body, or voice stimuli). If emotions are indeed represented at such an abstract level, then these abstract representations should also be activated by the memory of an emotional event. We tested this hypothesis by asking human participants to learn associations between emotional stimuli (videos of faces or bodies) and non-emotional stimuli (fractals). After successful learning, fMRI signals were recorded during the presentations of emotional stimuli and emotion-associated fractals. We tested whether emotions could be decoded from fMRI signals evoked by the fractal stimuli using a classifier trained on the responses to the emotional stimuli (and vice versa). This was implemented as a whole-brain searchlight, multivoxel activation pattern analysis, which revealed successful emotion decoding in four brain regions: posterior cingulate cortex (PCC), precuneus, MPFC, and angular gyrus. The same analysis run only on responses to emotional stimuli revealed clusters in PCC, precuneus, and MPFC. Multidimensional scaling analysis of the activation patterns revealed clear clustering of responses by emotion across stimulus types. Our results suggest that PCC, precuneus, and MPFC contain representations of emotions that can be evoked by stimuli that carry emotional information themselves or by stimuli that evoke memories of emotional stimuli, while angular gyrus is more likely to take part in emotional memory retrieval. Copyright © 2015 the authors 0270-6474/15/355655-09$15.00/0.

JPL Electronic Nose: From Sniffing Brain Cancer to Trouble in Space

NASA Technical Reports Server (NTRS)

Homer, Margie L.

2011-01-01

What Is An Electronic Nose? An array of non-specific chemical sensors, controlled and analyzed electronically, which mimics the action of the mammalian nose by recognizing patterns of response. An Enose: (1.) ENose measures background resistance in each sensor and establishes a baseline. (2.) Contaminant comes in contact with sensors on the sensing head. (3.) The sensing films, change physical properties, such as thickness or color, as air composition changes. (4.) Sensor response is recorded by a computer, the change in resistance is computed, and the distributed response pattern of the sensor array is used to identify gases and mixtures of gases. (5. Responses of the sensor array are analyzed and quantified using software developed for the task.

Screening of Biochemical and Molecular Mechanisms of Secondary Injury and Repair in the Brain after Experimental Blast-Induced Traumatic Brain Injury in Rats

DTIC Science & Technology

2013-01-01

Vimentin, complement component 1) with expression patterns bioinformatically consistent with those seen in Alzheimer’s disease and long-term...statistically significant associations with blast TBI at 2 h included Parkinson’s, Huntington’s, and Alzheimer’s disease , respectively suggesting...similarities in the early blast TBI response to those seen in important neurodegenerative diseases that have been linked to TBI.25 Comparison of 24 h

Effect of Magnitude Estimation of Pleasantness and Intensity on fMRI Activation to Taste

PubMed Central

Cerf-Ducastel, B.; Haase, L.; Murphy, C.

2012-01-01

The goal of the present study was to investigate whether the psychophysical evaluation of taste stimuli using magnitude estimation influences the pattern of cortical activation observed with neuroimaging. That is, whether different brain areas are involved in the magnitude estimation of pleasantness relative to the magnitude estimation of intensity. fMRI was utilized to examine the patterns of cortical activation involved in magnitude estimation of pleasantness and intensity during hunger in response to taste stimuli. During scanning, subjects were administered taste stimuli orally and were asked to evaluate the perceived pleasantness or intensity using the general Labeled Magnitude Scale (Green 1996, Bartoshuk et al. 2004). Image analysis was conducted using AFNI. Magnitude estimation of intensity and pleasantness shared common activations in the insula, rolandic operculum, and the medio dorsal nucleus of the thalamus. Globally, magnitude estimation of pleasantness produced significantly more activation than magnitude estimation of intensity. Areas differentially activated during magnitude estimation of pleasantness versus intensity included, e.g., the insula, the anterior cingulate gyrus, and putamen; suggesting that different brain areas were recruited when subjects made magnitude estimates of intensity and pleasantness. These findings demonstrate significant differences in brain activation during magnitude estimation of intensity and pleasantness to taste stimuli. An appreciation for the complexity of brain response to taste stimuli may facilitate a clearer understanding of the neural mechanisms underlying eating behavior and over consumption. PMID:23227271

Evidence for hubs in human functional brain networks

PubMed Central

Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N; Petersen, Steven E

2013-01-01

Summary Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: 1) finding network nodes that participate in multiple sub-networks of the brain, and 2) finding spatial locations where several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity. PMID:23972601

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

Prediction of human errors by maladaptive changes in event-related brain networks.

PubMed

Eichele, Tom; Debener, Stefan; Calhoun, Vince D; Specht, Karsten; Engel, Andreas K; Hugdahl, Kenneth; von Cramon, D Yves; Ullsperger, Markus

2008-04-22

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve approximately 30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations.

Prediction of human errors by maladaptive changes in event-related brain networks

PubMed Central

Eichele, Tom; Debener, Stefan; Calhoun, Vince D.; Specht, Karsten; Engel, Andreas K.; Hugdahl, Kenneth; von Cramon, D. Yves; Ullsperger, Markus

2008-01-01

Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional MRI and applying independent component analysis followed by deconvolution of hemodynamic responses, we studied error preceding brain activity on a trial-by-trial basis. We found a set of brain regions in which the temporal evolution of activation predicted performance errors. These maladaptive brain activity changes started to evolve ≈30 sec before the error. In particular, a coincident decrease of deactivation in default mode regions of the brain, together with a decline of activation in regions associated with maintaining task effort, raised the probability of future errors. Our findings provide insights into the brain network dynamics preceding human performance errors and suggest that monitoring of the identified precursor states may help in avoiding human errors in critical real-world situations. PMID:18427123

Perception of social synchrony induces mother-child gamma coupling in the social brain.

PubMed

Levy, Jonathan; Goldstein, Abraham; Feldman, Ruth

2017-07-01

The recent call to move from focus on one brain's functioning to two-brain communication initiated a search for mechanisms that enable two humans to coordinate brain response during social interactions. Here, we utilized the mother-child context as a developmentally salient setting to study two-brain coupling. Mothers and their 9-year-old children were videotaped at home in positive and conflictual interactions. Positive interactions were microcoded for social synchrony and conflicts for overall dialogical style. Following, mother and child underwent magnetoencephalography while observing the positive vignettes. Episodes of behavioral synchrony, compared to non-synchrony, increased gamma-band power in the superior temporal sulcus (STS), hub of social cognition, mirroring and mentalizing. This neural pattern was coupled between mother and child. Brain-to-brain coordination was anchored in behavioral synchrony; only during episodes of behavioral synchrony, but not during non-synchronous moments, mother's and child's STS gamma power was coupled. Importantly, neural synchrony was not found during observation of unfamiliar mother-child interaction Maternal empathic/dialogical conflict style predicted mothers' STS activations whereas child withdrawal predicted attenuated STS response in both partners. Results define a novel neural marker for brain-to-brain synchrony, highlight the role of rapid bottom-up oscillatory mechanisms for neural coupling and indicate that behavior-based processes may drive synchrony between two brains during social interactions. © The Author (2017). Published by Oxford University Press.

Global Brain Blood-Oxygen Level Responses to Autonomic Challenges in Obstructive Sleep Apnea

PubMed Central

Macey, Paul M.; Kumar, Rajesh; Ogren, Jennifer A.; Woo, Mary A.; Harper, Ronald M.

2014-01-01

Obstructive sleep apnea (OSA) is accompanied by brain injury, perhaps resulting from apnea-related hypoxia or periods of impaired cerebral perfusion. Perfusion changes can be determined indirectly by evaluation of cerebral blood volume and oxygenation alterations, which can be measured rapidly and non-invasively with the global blood oxygen level dependent (BOLD) signal, a magnetic resonance imaging procedure. We assessed acute BOLD responses in OSA subjects to pressor challenges that elicit cerebral blood flow changes, using a two-group comparative design with healthy subjects as a reference. We separately assessed female and male patterns, since OSA characteristics and brain injury differ between sexes. We studied 94 subjects, 37 with newly-diagnosed, untreated OSA (6 female (age mean ± std: 52.1±8.1 yrs; apnea/hypopnea index [AHI]: 27.7±15.6 events/hr and 31 male 54.3±8.4 yrs; AHI: 37.4±19.6 events/hr), and 20 female (age 50.5±8.1 yrs) and 37 male (age 45.6±9.2 yrs) healthy control subjects. We measured brain BOLD responses every 2 s while subjects underwent cold pressor, hand grip, and Valsalva maneuver challenges. The global BOLD signal rapidly changed after the first 2 s of each challenge, and differed in magnitude between groups to two challenges (cold pressor, hand grip), but not to the Valsalva maneuver (repeated measures ANOVA, p<0.05). OSA females showed greater differences from males in response magnitude and pattern, relative to healthy counterparts. Cold pressor BOLD signal increases (mean ± adjusted standard error) at the 8 s peak were: OSA 0.14±0.08% vs. Control 0.31±0.06%, and hand grip at 6 s were: OSA 0.08±0.03% vs. Control at 0.30±0.02%. These findings, indicative of reduced cerebral blood flow changes to autonomic challenges in OSA, complement earlier reports of altered resting blood flow and reduced cerebral artery responsiveness. Females are more affected than males, an outcome which may contribute to the sex-specific brain injury in the syndrome. PMID:25166862

DCE-MRI defined subvolumes of a brain metastatic lesion by principle component analysis and fuzzy-c-means clustering for response assessment of radiation therapy

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

Farjam, Reza; Tsien, Christina I.; Lawrence, Theodore S.

Purpose: To develop a pharmacokinetic modelfree framework to analyze the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data for assessment of response of brain metastases to radiation therapy. Methods: Twenty patients with 45 analyzable brain metastases had MRI scans prior to whole brain radiation therapy (WBRT) and at the end of the 2-week therapy. The volumetric DCE images covering the whole brain were acquired on a 3T scanner with approximately 5 s temporal resolution and a total scan time of about 3 min. DCE curves from all voxels of the 45 brain metastases were normalized and then temporally aligned. Amore » DCE matrix that is constructed from the aligned DCE curves of all voxels of the 45 lesions obtained prior to WBRT is processed by principal component analysis to generate the principal components (PCs). Then, the projection coefficient maps prior to and at the end of WBRT are created for each lesion. Next, a pattern recognition technique, based upon fuzzy-c-means clustering, is used to delineate the tumor subvolumes relating to the value of the significant projection coefficients. The relationship between changes in different tumor subvolumes and treatment response was evaluated to differentiate responsive from stable and progressive tumors. Performance of the PC-defined tumor subvolume was also evaluated by receiver operating characteristic (ROC) analysis in prediction of nonresponsive lesions and compared with physiological-defined tumor subvolumes. Results: The projection coefficient maps of the first three PCs contain almost all response-related information in DCE curves of brain metastases. The first projection coefficient, related to the area under DCE curves, is the major component to determine response while the third one has a complimentary role. In ROC analysis, the area under curve of 0.88 ± 0.05 and 0.86 ± 0.06 were achieved for the PC-defined and physiological-defined tumor subvolume in response assessment. Conclusions: The PC-defined subvolume of a brain metastasis could predict tumor response to therapy similar to the physiological-defined one, while the former is determined more rapidly for clinical decision-making support.« less

DCE-MRI defined subvolumes of a brain metastatic lesion by principle component analysis and fuzzy-c-means clustering for response assessment of radiation therapy

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

Farjam, Reza; Tsien, Christina I.; Lawrence, Theodore S.

2014-01-15

Purpose: To develop a pharmacokinetic modelfree framework to analyze the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) data for assessment of response of brain metastases to radiation therapy. Methods: Twenty patients with 45 analyzable brain metastases had MRI scans prior to whole brain radiation therapy (WBRT) and at the end of the 2-week therapy. The volumetric DCE images covering the whole brain were acquired on a 3T scanner with approximately 5 s temporal resolution and a total scan time of about 3 min. DCE curves from all voxels of the 45 brain metastases were normalized and then temporally aligned. Amore » DCE matrix that is constructed from the aligned DCE curves of all voxels of the 45 lesions obtained prior to WBRT is processed by principal component analysis to generate the principal components (PCs). Then, the projection coefficient maps prior to and at the end of WBRT are created for each lesion. Next, a pattern recognition technique, based upon fuzzy-c-means clustering, is used to delineate the tumor subvolumes relating to the value of the significant projection coefficients. The relationship between changes in different tumor subvolumes and treatment response was evaluated to differentiate responsive from stable and progressive tumors. Performance of the PC-defined tumor subvolume was also evaluated by receiver operating characteristic (ROC) analysis in prediction of nonresponsive lesions and compared with physiological-defined tumor subvolumes. Results: The projection coefficient maps of the first three PCs contain almost all response-related information in DCE curves of brain metastases. The first projection coefficient, related to the area under DCE curves, is the major component to determine response while the third one has a complimentary role. In ROC analysis, the area under curve of 0.88 ± 0.05 and 0.86 ± 0.06 were achieved for the PC-defined and physiological-defined tumor subvolume in response assessment. Conclusions: The PC-defined subvolume of a brain metastasis could predict tumor response to therapy similar to the physiological-defined one, while the former is determined more rapidly for clinical decision-making support.« less

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.

Common and Distinct Neural Mechanisms of Attentional Switching and Response Conflict

PubMed Central

Kim, Chobok; Johnson, Nathan F.; Gold, Brian T.

2012-01-01

The human capacities for overcoming prepotent actions and flexibly switching between tasks represent cornerstones of cognitive control. Functional neuroimaging has implicated a diverse set of brain regions contributing to each of these cognitive control processes. However, the extent to which attentional switching and response conflict draw on shared or distinct neural mechanisms remains unclear. The current study examined the neural correlates of response conflict and attentional switching using event-related functional magnetic resonance imaging (fMRI) and a fully randomized 2×2 design. We manipulated an arrow-word version of the Stroop task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict. These results suggest that the brain makes use of shared frontal regions, but can dynamically modulate the connectivity patterns of some of those regions, to deal with attentional switching and response conflict. PMID:22750124

Common and distinct neural mechanisms of attentional switching and response conflict.

PubMed

Kim, Chobok; Johnson, Nathan F; Gold, Brian T

2012-08-21

The human capacities for overcoming prepotent actions and flexibly switching between tasks represent cornerstones of cognitive control. Functional neuroimaging has implicated a diverse set of brain regions contributing to each of these cognitive control processes. However, the extent to which attentional switching and response conflict draw on shared or distinct neural mechanisms remains unclear. The current study examined the neural correlates of response conflict and attentional switching using event-related functional magnetic resonance imaging (fMRI) and a fully randomized 2×2 design. We manipulated an arrow-word version of the Stroop task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict. These results suggest that the brain makes use of shared frontal regions, but can dynamically modulate the connectivity patterns of some of those regions, to deal with attentional switching and response conflict. Copyright © 2012 Elsevier B.V. All rights reserved.

Cholinesterase (ChE) response and related mortality among birds fed ChE inhibitors

USGS Publications Warehouse

Ludke, J.L.; Hill, E.F.; Dieter, M.P.

1975-01-01

Patterns of mortality and inhibition of brain and plasma ChE in birds treated with ChE inhibitors were studied in an attempt to determine the validity of using ChE activity as a monitoring and diagnostic technique. Analysis of brain ChE activity proved to be reliable for diagnosing and monitoring effects of selected ChE inhibitors in birds. Brain ChE inhibition exceeding 20% indicated exposure, and inhibition greater than 50% was sufficient for diagnosing cause of death. Individuals that died from dietary exposure to parathion or carbofuran had brain ChE activities below 55% of normal; although individuals could survive with brain ChE activity lower than 50%. Problems associated with collection, storage, and analysis of tissues for ChE activity are discussed.

Neural Bases Of Food Perception: Coordinate-Based Meta-Analyses Of Neuroimaging Studies In Multiple Modalities

PubMed Central

Huerta, Claudia I; Sarkar, Pooja R; Duong, Timothy Q.; Laird, Angela R; Fox, Peter T

2013-01-01

Objective The purpose of this study was to compare the results of the three food-cue paradigms most commonly used for functional neuroimaging studies to determine: i) commonalities and differences in the neural response patterns by paradigm; and, ii) the relative robustness and reliability of responses to each paradigm. Design and Methods functional magnetic resonance imaging (fMRI) studies using standardized stereotactic coordinates to report brain responses to food cues were identified using on-line databases. Studies were grouped by food-cue modality as: i) tastes (8 studies); ii) odors (8 studies); and, iii) images (11 studies). Activation likelihood estimation (ALE) was used to identify statistically reliable regional responses within each stimulation paradigm. Results Brain response distributions were distinctly different for the three stimulation modalities, corresponding to known differences in location of the respective primary and associative cortices. Visual stimulation induced the most robust and extensive responses. The left anterior insula was the only brain region reliably responding to all three stimulus categories. Conclusions These findings suggest visual food-cue paradigm as promising candidate for imaging studies addressing the neural substrate of therapeutic interventions. PMID:24174404

Natural variation in maternal care and cross-tissue patterns of oxytocin receptor gene methylation in rats.

PubMed

Beery, Annaliese K; McEwen, Lisa M; MacIsaac, Julia L; Francis, Darlene D; Kobor, Michael S

2016-01-01

This article is part of a Special Issue "Parental Care". Since the first report of maternal care effects on DNA methylation in rats, epigenetic modifications of the genome in response to life experience have become the subject of intense focus across many disciplines. Oxytocin receptor expression varies in response to early experience, and both oxytocin signaling and methylation status of the oxytocin receptor gene (Oxtr) in blood have been related to disordered social behavior. It is unknown whether Oxtr DNA methylation varies in response to early life experience, and whether currently employed peripheral measures of Oxtr methylation reflect variation in the brain. We examined the effects of early life rearing experience via natural variation in maternal licking and grooming during the first week of life on behavior, physiology, gene expression, and epigenetic regulation of Oxtr across blood and brain tissues (mononucleocytes, hippocampus, striatum, and hypothalamus). Rats reared by "high" licking-grooming (HL) and "low" licking-grooming (LL) rat dams exhibited differences across study outcomes: LL offspring were more active in behavioral arenas, exhibited lower body mass in adulthood, and showed reduced corticosterone responsivity to a stressor. Oxtr DNA methylation was significantly lower at multiple CpGs in the blood of LL versus HL males, but no differences were found in the brain. Across groups, Oxtr transcript levels in the hypothalamus were associated with reduced corticosterone secretion in response to stress, congruent with the role of oxytocin signaling in this region. Methylation of specific CpGs at a high or low level was consistent across tissues, especially within the brain. However, individual variation in DNA methylation relative to these global patterns was not consistent across tissues. These results suggest that blood Oxtr DNA methylation may reflect early experience of maternal care, and that Oxtr methylation across tissues is highly concordant for specific CpGs, but that inferences across tissues are not supported for individual variation in Oxtr methylation. Copyright © 2015 Elsevier Inc. All rights reserved.

Natural variation in maternal care and cross-tissue patterns of oxytocin receptor gene methylation in rats

PubMed Central

Beery, Annaliese K.; McEwen, Lisa M.; MacIsaac, Julia L; Francis, Darlene D.; Kobor, Michael S.

2015-01-01

Since the first report of maternal care effects on DNA methylation in rats, epigenetic modifications of the genome in response to life experience have become the subject of intense focus across many disciplines. Oxytocin receptor expression varies in response to early experience, and both oxytocin signaling and methylation status of the oxytocin receptor gene (Oxtr) in blood have been related to disordered social behavior. It is unknown whether Oxtr methylation varies in response to early life experience, and whether currently employed peripheral measures of Oxtr methylation reflect variation in the brain. We examined the effects of early life rearing experience via natural variation in maternal licking and grooming during the first week of life on behavior, physiology, gene expression, and epigenetic regulation of Oxtr across blood and brain tissues (mononucleocytes, hippocampus, striatum, and hypothalamus). Rats reared by “high” licking-grooming (HL) and “low” licking-grooming (LL) rat dams exhibited differences across study outcomes: LL offspring were more active in behavioral arenas, exhibited lower body mass in adulthood, and showed reduced corticosterone responsivity to a stressor. Oxtr methylation was significantly lower at multiple CpGs in the blood of LL versus HL rats, but no differences were found in the brain. Across groups, Oxtr transcript levels in the hypothalamus were associated with reduced corticosterone secretion in response to stress, congruent with the role of oxytocin signaling in this region. Methylation of specific CpGs at a high or low level was consistent across tissues, especially within the brain. However, individual variation in methylation relative to these global patterns was not consistent across tissues. These results suggest that blood Oxtr methylation may reflect early experience of maternal care, and that Oxtr methylation across tissues is highly concordant for specific CpGs, but that inferences across tissues are not supported for individual variation in Oxtr methylation. PMID:26122287

Functional magnetic resonance imaging in awake transgenic fragile X rats: evidence of dysregulation in reward processing in the mesolimbic/habenular neural circuit.

PubMed

Kenkel, W M; Yee, J R; Moore, K; Madularu, D; Kulkarni, P; Gamber, K; Nedelman, M; Ferris, C F

2016-03-22

Anxiety and social deficits, often involving communication impairment, are fundamental clinical features of fragile X syndrome. There is growing evidence that dysregulation in reward processing is a contributing factor to the social deficits observed in many psychiatric disorders. Hence, we hypothesized that transgenic fragile X mental retardation 1 gene (fmr1) KO (FX) rats would display alterations in reward processing. To this end, awake control and FX rats were imaged for changes in blood oxygen level dependent (BOLD) signal intensity in response to the odor of almond, a stimulus to elicit the innate reward response. Subjects were 'odor naive' to this evolutionarily conserved stimulus. The resulting changes in brain activity were registered to a three-dimensional segmented, annotated rat atlas delineating 171 brain regions. Both wild-type (WT) and FX rats showed robust brain activation to a rewarding almond odor, though FX rats showed an altered temporal pattern and tended to have a higher number of voxels with negative BOLD signal change from baseline. This pattern of greater negative BOLD was especially apparent in the Papez circuit, critical to emotional processing and the mesolimbic/habenular reward circuit. WT rats showed greater positive BOLD response in the supramammillary area, whereas FX rats showed greater positive BOLD response in the dorsal lateral striatum, and greater negative BOLD response in the retrosplenial cortices, the core of the accumbens and the lateral preoptic area. When tested in a freely behaving odor-investigation paradigm, FX rats failed to show the preference for almond odor which typifies WT rats. However, FX rats showed investigation profiles similar to WT when presented with social odors. These data speak to an altered processing of this highly salient novel odor in the FX phenotype and lend further support to the notion that altered reward systems in the brain may contribute to fragile X syndrome symptomology.

fMRI responses to Jung's Word Association Test: implications for theory, treatment and research.

PubMed

Petchkovsky, Leon; Petchkovsky, Michael; Morris, Philip; Dickson, Paul; Montgomery, Danielle; Dwyer, Jonathan; Burnett, Patrick

2013-06-01

Jung's Word Association Test was performed under fMRI conditions by 12 normal subjects. Pooled complexed responses were contrasted against pooled neutral ones. The fMRI activation pattern of this generic 'complexed response' was very strong (corrected Z scores ranging from 4.90 to 5.69). The activation pattern in each hemisphere includes mirror neurone areas that track 'otherness' (perspectival empathy), anterior insula (both self-awareness and emotional empathy), and cingulated gyrus (self-awareness and conflict-monitoring). These are the sites described by Siegel and colleagues as the 'resonance circuitry' in the brain which is central to mindfulness (awareness of self) and empathy (sense of the other), negotiations between self awareness and the 'internal other'. But there is also an interhemispheric dialogue. Within 3 seconds, the left hemisphere over-rides the right (at least in our normal subjects). Mindfulness and empathy are central to good psychotherapy, and complexes can be windows of opportunity if left-brain hegemony is resisted. This study sets foundations for further research: (i) QEEG studies (with their finer temporal resolution) of complexed responses in normal subjects (ii) QEEG and fMRI studies of complexed responses in other conditions, like schizophrenia, PTSD, disorders of self organization. © 2013, The Society of Analytical Psychology.

Frequency-specific alterations in functional connectivity in treatment-resistant and -sensitive major depressive disorder.

PubMed

He, Zongling; Cui, Qian; Zheng, Junjie; Duan, Xujun; Pang, Yajing; Gao, Qing; Han, Shaoqiang; Long, Zhiliang; Wang, Yifeng; Li, Jiao; Wang, Xiao; Zhao, Jingping; Chen, Huafu

2016-11-01

Major depressive disorder (MDD) may involve alterations in brain functional connectivity in multiple neural circuits and present large-scale network dysfunction. Patients with treatment-resistant depression (TRD) and treatment-sensitive depression (TSD) show different responses to antidepressants and aberrant brain functions. This study aims to investigate functional connectivity patterns of TRD and TSD at the whole brain resting state. Seventeen patients with TRD, 17 patients with TSD, and 17 healthy controls matched with age, gender, and years of education were recruited in this study. The brain was divided using an automated anatomical labeling atlas into 90 regions of interest, which were used to construct the entire brain functional networks. An analysis method called network-based statistic was used to explore the dysconnected subnetworks of TRD and TSD at different frequency bands. At resting state, TSD and TRD present characteristic patterns of network dysfunction at special frequency bands. The dysconnected subnetwork of TSD mainly lies in the fronto-parietal top-down control network. Moreover, the abnormal neural circuits of TRD are extensive and complex. These circuits not only depend on the abnormal affective network but also involve other networks, including salience network, auditory network, visual network, and language processing cortex. Our findings reflect that the pathological mechanism of TSD may refer to impairment in cognitive control, whereas TRD mainly triggers the dysfunction of emotion processing and affective cognition. This study reveals that differences in brain functional connectivity at resting state reflect distinct pathophysiological mechanisms in TSD and TRD. These findings may be helpful in differentiating two types of MDD and predicting treatment responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inter-individual variability in response to non-invasive brain stimulation paradigms.

PubMed

López-Alonso, Virginia; Cheeran, Binith; Río-Rodríguez, Dan; Fernández-Del-Olmo, Miguel

2014-01-01

Non-invasive Brain Stimulation (NIBS) paradigms are unique in their ability to safely modulate cortical plasticity for experimental or therapeutic applications. However, increasingly, there is concern regarding inter-individual variability in the efficacy and reliability of these paradigms. Inter-individual variability in response to NIBS paradigms would be better explained if a multimodal distribution was assumed. In three different sessions for each subject (n = 56), we studied the Paired Associative Stimulation (PAS25), Anodal transcranial DC stimulation (AtDCS) and intermittent theta burst stimulation (iTBS) protocols. We applied cluster analysis to detect distinct patterns of response between individuals. Furthermore, we tested whether baseline TMS measures (such as short intracortical inhibition (SICI), resting motor threshold (RMT)) or factors such as time of day could predict each individual's response pattern. All three paradigms show similar efficacy over the first hour post stimulation--there is no significant effect on excitatory or inhibitory circuits for the whole sample, and AtDCS fares no better than iTBS or PAS25. Cluster analysis reveals a bimodal response pattern--but only 39%, 45% and 43% of subjects responded as expected to PAS25, AtDCS, and iTBS respectively. Pre-stimulation SICI accounted for 10% of the variability in response to PAS25, but no other baseline measures were predictive of response. Finally, we report implications for sample size calculation and the remarkable effect of sample enrichment. The implications of the high rate of 'dose-failure' for experimental and therapeutic applications of NIBS lead us to conclude that addressing inter-individual variability is a key area of concern for the field. Copyright © 2014 Elsevier Inc. All rights reserved.

Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures

PubMed Central

Ye, Zheng; Rae, Charlotte L.; Nombela, Cristina; Ham, Timothy; Rittman, Timothy; Jones, Peter Simon; Rodríguez, Patricia Vázquez; Coyle‐Gilchrist, Ian; Regenthal, Ralf; Altena, Ellemarije; Housden, Charlotte R.; Maxwell, Helen; Sahakian, Barbara J.; Barker, Roger A.; Robbins, Trevor W.

2016-01-01

Abstract Recent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double‐blind randomized three‐way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40 mg atomoxetine, 30 mg citalopram, or placebo. Diffusion‐weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave‐one‐out cross‐validation (LOOCV) to predict patients’ responses in terms of improved stopping efficiency. We identified two optimal models: (1) a “clinical” model that predicted the response of an individual patient with 77–79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion‐weighted imaging scan; and (2) a “mechanistic” model that explained the behavioral response with 85% accuracy for each drug, using drug‐induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features. Hum Brain Mapp 37:1026–1037, 2016. © 2016 Wiley Periodicals, Inc. PMID:26757216

Functional brain connectivity when cooperation fails.

PubMed

Balconi, Michela; Vanutelli, Maria Elide; Gatti, Laura

2018-06-01

Functional connectivity during cooperative actions is an important topic in social neuroscience that has yet to be answered. Here, we examined the effects of administration of (fictitious) negative social feedback in relation to cooperative capabilities. Cognitive performance and neural activation underlying the execution of joint actions was recorded with functional near-infrared spectroscopy (fNIRS) on prefrontal regions during a task where pairs of participants received negative feedback after their joint action. Performance (error rates (ERs) and response times (RTs)) and intra- and inter-brain connectivity indices were computed, along with the ConIndex (inter-brain/intra-brain connectivity). Finally, correlational measures were considered to assess the relation between these different measures. Results showed that the negative feedback was able to modulate participants' responses for both behavioral and neural components. Cognitive performance was decreased after the feedback. Moreover, decreased inter-brain connectivity and increased intra-brain connectivity was induced by the feedback, whereas the cooperative task pre-feedback condition was able to increase the brain-to-brain coupling, mainly localized within the dorsolateral prefrontal cortex (DLPFC). Finally, the presence of significant correlations between RTs and inter-brain connectivity revealed that ineffective joint action produces the worst cognitive performance and a more 'individual strategy' for brain activity, limiting the inter-brain connectivity. The present study provides a significant contribution to the identification of patterns of intra- and inter-brain functional connectivity when negative social reinforcement is provided in relation to cooperative actions. Copyright © 2018 Elsevier Inc. All rights reserved.

Extracellular Mitochondria and Mitochondrial Components Act as Damage-Associated Molecular Pattern Molecules in the Mouse Brain.

PubMed

Wilkins, Heather M; Koppel, Scott J; Weidling, Ian W; Roy, Nairita; Ryan, Lauren N; Stanford, John A; Swerdlow, Russell H

2016-12-01

Mitochondria and mitochondrial debris are found in the brain's extracellular space, and extracellular mitochondrial components can act as damage associated molecular pattern (DAMP) molecules. To characterize the effects of potential mitochondrial DAMP molecules on neuroinflammation, we injected either isolated mitochondria or mitochondrial DNA (mtDNA) into hippocampi of C57BL/6 mice and seven days later measured markers of inflammation. Brains injected with whole mitochondria showed increased Tnfα and decreased Trem2 mRNA, increased GFAP protein, and increased NFκB phosphorylation. Some of these effects were also observed in brains injected with mtDNA (decreased Trem2 mRNA, increased GFAP protein, and increased NFκB phosphorylation), and mtDNA injection also caused several unique changes including increased CSF1R protein and AKT phosphorylation. To further establish the potential relevance of this response to Alzheimer's disease (AD), a brain disorder characterized by neurodegeneration, mitochondrial dysfunction, and neuroinflammation we also measured App mRNA, APP protein, and Aβ 1-42 levels. We found mitochondria (but not mtDNA) injections increased these parameters. Our data show that in the mouse brain extracellular mitochondria and its components can induce neuroinflammation, extracellular mtDNA or mtDNA-associated proteins can contribute to this effect, and mitochondria derived-DAMP molecules can influence AD-associated biomarkers.

Neuroticism modulates brain visuo-vestibular and anxiety systems during a virtual rollercoaster task.

PubMed

Riccelli, Roberta; Indovina, Iole; Staab, Jeffrey P; Nigro, Salvatore; Augimeri, Antonio; Lacquaniti, Francesco; Passamonti, Luca

2017-02-01

Different lines of research suggest that anxiety-related personality traits may influence the visual and vestibular control of balance, although the brain mechanisms underlying this effect remain unclear. To our knowledge, this is the first functional magnetic resonance imaging (fMRI) study that investigates how individual differences in neuroticism and introversion, two key personality traits linked to anxiety, modulate brain regional responses and functional connectivity patterns during a fMRI task simulating self-motion. Twenty-four healthy individuals with variable levels of neuroticism and introversion underwent fMRI while performing a virtual reality rollercoaster task that included two main types of trials: (1) trials simulating downward or upward self-motion (vertical motion), and (2) trials simulating self-motion in horizontal planes (horizontal motion). Regional brain activity and functional connectivity patterns when comparing vertical versus horizontal motion trials were correlated with personality traits of the Five Factor Model (i.e., neuroticism, extraversion-introversion, openness, agreeableness, and conscientiousness). When comparing vertical to horizontal motion trials, we found a positive correlation between neuroticism scores and regional activity in the left parieto-insular vestibular cortex (PIVC). For the same contrast, increased functional connectivity between the left PIVC and right amygdala was also detected as a function of higher neuroticism scores. Together, these findings provide new evidence that individual differences in personality traits linked to anxiety are significantly associated with changes in the activity and functional connectivity patterns within visuo-vestibular and anxiety-related systems during simulated vertical self-motion. Hum Brain Mapp 38:715-726, 2017. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Assessment of pedophilia using hemodynamic brain response to sexual stimuli.

PubMed

Ponseti, Jorge; Granert, Oliver; Jansen, Olav; Wolff, Stephan; Beier, Klaus; Neutze, Janina; Deuschl, Günther; Mehdorn, Hubertus; Siebner, Hartwig; Bosinski, Hartmut

2012-02-01

Accurately assessing sexual preference is important in the treatment of child sex offenders. Phallometry is the standard method to identify sexual preference; however, this measure has been criticized for its intrusiveness and limited reliability. To evaluate whether spatial response pattern to sexual stimuli as revealed by a change in the blood oxygen level-dependent signal facilitates the identification of pedophiles. During functional magnetic resonance imaging, pedophilic and nonpedophilic participants were briefly exposed to same- and opposite-sex images of nude children and adults. We calculated differences in blood oxygen level-dependent signals to child and adult sexual stimuli for each participant. The corresponding contrast images were entered into a group analysis to calculate whole-brain difference maps between groups. We calculated an expression value that corresponded to the group result for each participant. These expression values were submitted to 2 different classification algorithms: Fisher linear discriminant analysis and κ -nearest neighbor analysis. This classification procedure was cross-validated using the leave-one-out method. Section of Sexual Medicine, Medical School, Christian Albrechts University of Kiel, Kiel, Germany. We recruited 24 participants with pedophilia who were sexually attracted to either prepubescent girls (n = 11) or prepubescent boys (n = 13) and 32 healthy male controls who were sexually attracted to either adult women (n = 18) or adult men (n = 14). Sensitivity and specificity scores of the 2 classification algorithms. The highest classification accuracy was achieved by Fisher linear discriminant analysis, which showed a mean accuracy of 95% (100% specificity, 88% sensitivity). Functional brain response patterns to sexual stimuli contain sufficient information to identify pedophiles with high accuracy. The automatic classification of these patterns is a promising objective tool to clinically diagnose pedophilia.

Parametric fMRI of paced motor responses uncovers novel whole-brain imaging biomarkers in spinocerebellar ataxia type 3.

PubMed

Duarte, João Valente; Faustino, Ricardo; Lobo, Mercês; Cunha, Gil; Nunes, César; Ferreira, Carlos; Januário, Cristina; Castelo-Branco, Miguel

2016-10-01

Machado-Joseph Disease, inherited type 3 spinocerebellar ataxia (SCA3), is the most common form worldwide. Neuroimaging and neuropathology have consistently demonstrated cerebellar alterations. Here we aimed to discover whole-brain functional biomarkers, based on parametric performance-level-dependent signals. We assessed 13 patients with early SCA3 and 14 healthy participants. We used a combined parametric behavioral/functional neuroimaging design to investigate disease fingerprints, as a function of performance levels, coupled with structural MRI and voxel-based morphometry. Functional magnetic resonance imaging (fMRI) was designed to parametrically analyze behavior and neural responses to audio-paced bilateral thumb movements at temporal frequencies of 1, 3, and 5 Hz. Our performance-level-based design probing neuronal correlates of motor coordination enabled the discovery that neural activation and behavior show critical loss of parametric modulation specifically in SCA3, associated with frequency-dependent cortico/subcortical activation/deactivation patterns. Cerebellar/cortical rate-dependent dissociation patterns could clearly differentiate between groups irrespective of grey matter loss. Our findings suggest functional reorganization of the motor network and indicate a possible role of fMRI as a tool to monitor disease progression in SCA3. Accordingly, fMRI patterns proved to be potential biomarkers in early SCA3, as tested by receiver operating characteristic analysis of both behavior and neural activation at different frequencies. Discrimination analysis based on BOLD signal in response to the applied parametric finger-tapping task significantly often reached >80% sensitivity and specificity in single regions-of-interest.Functional fingerprints based on cerebellar and cortical BOLD performance dependent signal modulation can thus be combined as diagnostic and/or therapeutic targets in hereditary ataxia. Hum Brain Mapp 37:3656-3668, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities

PubMed Central

Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2015-01-01

Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal–occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention. PMID:26419418

Mapping of Courtship Behavior-Induced Neural Activity in the Thoracic Ganglia of Silkmoth Bombyx mori by an Immediate Early Gene, Hr38.

PubMed

Morishita, Koudai; Iwami, Masafumi; Kiya, Taketoshi

2018-06-01

In the central nervous system of insects, motor patterns are generated in the thoracic ganglia under the control of brain, where sensory information is integrated and behavioral decisions are made. Previously, we established neural activity-mapping methods using an immediate early gene, BmHr38, as a neural activity marker in the brain of male silkmoth Bombyx mori. In the present study, to gain insights into neural mechanisms of motor-pattern generation in the thoracic ganglia, we investigated expression of BmHr38 in response to sex pheromone-induced courtship behavior. Levels of BmHr38 expression were strongly correlated between the brain and thoracic ganglia, suggesting that neural activity in the thoracic ganglia is tightly controlled by the brain. In situ hybridization of BmHr38 revealed that 20-30% of thoracic neurons are activated by courtship behavior. Using serial sections, we constructed a comprehensive map of courtship behaviorinduced activity in the thoracic ganglia. These results provide important clues into how complex courtship behavior is generated in the neural circuits of thoracic ganglia.

Task-evoked brain functional magnetic susceptibility mapping by independent component analysis (χICA).

PubMed

Chen, Zikuan; Calhoun, Vince D

2016-03-01

Conventionally, independent component analysis (ICA) is performed on an fMRI magnitude dataset to analyze brain functional mapping (AICA). By solving the inverse problem of fMRI, we can reconstruct the brain magnetic susceptibility (χ) functional states. Upon the reconstructed χ dataspace, we propose an ICA-based brain functional χ mapping method (χICA) to extract task-evoked brain functional map. A complex division algorithm is applied to a timeseries of fMRI phase images to extract temporal phase changes (relative to an OFF-state snapshot). A computed inverse MRI (CIMRI) model is used to reconstruct a 4D brain χ response dataset. χICA is implemented by applying a spatial InfoMax ICA algorithm to the reconstructed 4D χ dataspace. With finger-tapping experiments on a 7T system, the χICA-extracted χ-depicted functional map is similar to the SPM-inferred functional χ map by a spatial correlation of 0.67 ± 0.05. In comparison, the AICA-extracted magnitude-depicted map is correlated with the SPM magnitude map by 0.81 ± 0.05. The understanding of the inferiority of χICA to AICA for task-evoked functional map is an ongoing research topic. For task-evoked brain functional mapping, we compare the data-driven ICA method with the task-correlated SPM method. In particular, we compare χICA with AICA for extracting task-correlated timecourses and functional maps. χICA can extract a χ-depicted task-evoked brain functional map from a reconstructed χ dataspace without the knowledge about brain hemodynamic responses. The χICA-extracted brain functional χ map reveals a bidirectional BOLD response pattern that is unavailable (or different) from AICA. Copyright © 2016 Elsevier B.V. All rights reserved.

On the same wavelength: predictable language enhances speaker-listener brain-to-brain synchrony in posterior superior temporal gyrus.

PubMed

Dikker, Suzanne; Silbert, Lauren J; Hasson, Uri; Zevin, Jason D

2014-04-30

Recent research has shown that the degree to which speakers and listeners exhibit similar brain activity patterns during human linguistic interaction is correlated with communicative success. Here, we used an intersubject correlation approach in fMRI to test the hypothesis that a listener's ability to predict a speaker's utterance increases such neural coupling between speakers and listeners. Nine subjects listened to recordings of a speaker describing visual scenes that varied in the degree to which they permitted specific linguistic predictions. In line with our hypothesis, the temporal profile of listeners' brain activity was significantly more synchronous with the speaker's brain activity for highly predictive contexts in left posterior superior temporal gyrus (pSTG), an area previously associated with predictive auditory language processing. In this region, predictability differentially affected the temporal profiles of brain responses in the speaker and listeners respectively, in turn affecting correlated activity between the two: whereas pSTG activation increased with predictability in the speaker, listeners' pSTG activity instead decreased for more predictable sentences. Listeners additionally showed stronger BOLD responses for predictive images before sentence onset, suggesting that highly predictable contexts lead comprehenders to preactivate predicted words.

Event-related functional MRI: Past, present, and future

PubMed Central

Rosen, Bruce R.; Buckner, Randy L.; Dale, Anders M.

1998-01-01

The past two decades have seen an enormous growth in the field of human brain mapping. Investigators have extensively exploited techniques such as positron emission tomography and MRI to map patterns of brain activity based on changes in cerebral hemodynamics. However, until recently, most studies have investigated equilibrium changes in blood flow measured over time periods upward of 1 min. The advent of high-speed MRI methods, capable of imaging the entire brain with a temporal resolution of a few seconds, allows for brain mapping based on more transient aspects of the hemodynamic response. Today it is now possible to map changes in cerebrovascular parameters essentially in real time, conferring the ability to observe changes in brain state that occur over time periods of seconds. Furthermore, because robust hemodynamic alterations are detectable after neuronal stimuli lasting only a few tens of milliseconds, a new class of task paradigms designed to measure regional responses to single sensory or cognitive events can now be studied. Such “event related” functional MRI should provide for fundamentally new ways to interrogate brain function, and allow for the direct comparison and ultimately integration of data acquired by using more traditional behavioral and electrophysiological methods. PMID:9448240

Stress-induced brain histone H3 phosphorylation: contribution of the intensity of stressors and length of exposure.

PubMed

Rotllant, David; Pastor-Ciurana, Jordi; Armario, Antonio

2013-05-01

Expression of c-fos is used for the characterization of brain areas activated by stressors. Recently, some epigenetic markers associated with enhanced transcription have been identified that may be also useful to detect neuronal populations important for the processing of stressors: phosphorylation of histone H3 in serine 10 or 28 (pH3S₁₀ or pH3S₂₈). Then, we compared in rats the response to stress of c-fos and these epigenetic changes. More specifically, we studied the influence of the type of stressor (novel environment vs. immobilization, IMO) and the dynamics of the response to IMO. Stress increased pH3S₁₀ positive neurons, with a more restricted pattern than that of c-fos, both in terms of brain areas activated and number of positive neurons. Changes in pH3S₁₀ showed a maximum at 30 min, then progressively declining in most areas in spite of the persistence of IMO. Moreover, the decline was in general more sensitive than c-fos to the termination of IMO. The pattern of pH3S₂₈ was even more restricted that of pH3S₁₀, but they showed co-localization. The present data demonstrate a more selective pattern of stress-induced histone H3 phosphorylation than c-fos. The factors determining such a selectivity and its biological meaning remain to be studied. © 2013 International Society for Neurochemistry.

Markers of oxidative damage to lipids, nucleic acids and proteins and antioxidant enzymes activities in Alzheimer's disease brain: A meta-analysis in human pathological specimens.

PubMed

Zabel, Matthew; Nackenoff, Alex; Kirsch, Wolff M; Harrison, Fiona E; Perry, George; Schrag, Matthew

2018-02-01

Oxidative stress and decreased cellular responsiveness to oxidative stress are thought to influence brain aging and Alzheimer's disease, but the specific patterns of oxidative damage and the underlying mechanism leading to this damage are not definitively known. The objective of this study was to define the pattern of changes in oxidative-stress related markers by brain region in human Alzheimer's disease and mild cognitive impairment brain tissue. Observational case-control studies were identified from systematic queries of PubMed, ISI Web of Science and Scopus databases and studies were evaluated with appropriate quality measures. The data was used to construct a region-by-region meta-analysis of malondialdehyde, 4-hydroxynonenal, protein carbonylation, 8-hydroxyguanine levels and superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase activities. We also evaluated ascorbic acid, tocopherol, uric acid and glutathione levels. The analysis was complicated in several cases by publication bias and/or outlier data. We found that malondialdehyde levels were slightly increased in the temporal and occipital lobes and hippocampus, but this analysis was significantly impacted by publication bias. 4-hydroxynonenal levels were unchanged in every brain region. There was no change in 8-hydroxyguanine level in any brain region and protein carbonylation levels were unchanged except for a slight increase in the occipital lobe. Superoxide dismutase, glutathione peroxidase and reductase and catalase activities were not decreased in any brain region. There was limited data reporting non-enzymatic antioxidant levels in Alzheimer's disease brain, although glutathione and tocopherol levels appear to be unchanged. Minimal quantitative data is available from brain tissue from patients with mild cognitive impairment. While there is modest evidence supporting minor regional changes in markers of oxidative damage, this analysis fails to identify a consistent pattern of pro-oxidative changes and accumulation of oxidative damage in bulk tissue analysis in the setting of Alzheimer's disease, as has been widely reported. Copyright © 2017 Elsevier Inc. All rights reserved.

Hippocampal Context Processing during Acquisition of a Predictive Learning Task Is Associated with Renewal in Extinction Recall.

PubMed

Lissek, Silke; Glaubitz, Benjamin; Schmidt-Wilcke, Tobias; Tegenthoff, Martin

2016-05-01

Renewal is defined as the recovery of an extinguished response if extinction and retrieval contexts differ. The context dependency of extinction, as demonstrated by renewal, has important implications for extinction-based therapies. Persons showing renewal (REN) exhibit higher hippocampal activation during extinction in associative learning than those without renewal (NOREN), demonstrating hippocampal context processing, and recruit ventromedial pFC in retrieval. Apart from these findings, brain processes generating renewal remain largely unknown. Conceivably, processing differences in task-relevant brain regions that ultimately lead to renewal may occur already in initial acquisition of associations. Therefore, in two fMRI studies, we investigated overall brain activation and hippocampal activation in REN and NOREN during acquisition of an associative learning task in response to presentation of a context alone or combined with a cue. Results of two studies demonstrated significant activation differences between the groups: In Study 1, a support vector machine classifier correctly assigned participants' brain activation patterns to REN and NOREN groups, respectively. In Study 2, REN and NOREN showed similar hippocampal involvement during context-only presentation, suggesting processing of novelty, whereas overall hippocampal activation to the context-cue compound, suggesting compound encoding, was higher in REN. Positive correlations between hippocampal activation and renewal level indicated more prominent hippocampal processing in REN. Results suggest that hippocampal processing of the context-cue compound rather than of context only during initial learning is related to a subsequent renewal effect. Presumably, REN participants use distinct encoding strategies during acquisition of context-related tasks, which reflect in their brain activation patterns and contribute to a renewal effect.

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

PubMed

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

2012-04-02

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

Perception of social synchrony induces mother–child gamma coupling in the social brain

PubMed Central

Levy, Jonathan; Goldstein, Abraham

2017-01-01

Abstract The recent call to move from focus on one brain’s functioning to two-brain communication initiated a search for mechanisms that enable two humans to coordinate brain response during social interactions. Here, we utilized the mother–child context as a developmentally salient setting to study two-brain coupling. Mothers and their 9-year-old children were videotaped at home in positive and conflictual interactions. Positive interactions were microcoded for social synchrony and conflicts for overall dialogical style. Following, mother and child underwent magnetoencephalography while observing the positive vignettes. Episodes of behavioral synchrony, compared to non-synchrony, increased gamma-band power in the superior temporal sulcus (STS), hub of social cognition, mirroring and mentalizing. This neural pattern was coupled between mother and child. Brain-to-brain coordination was anchored in behavioral synchrony; only during episodes of behavioral synchrony, but not during non-synchronous moments, mother’s and child's STS gamma power was coupled. Importantly, neural synchrony was not found during observation of unfamiliar mother-child interaction Maternal empathic/dialogical conflict style predicted mothers’ STS activations whereas child withdrawal predicted attenuated STS response in both partners. Results define a novel neural marker for brain-to-brain synchrony, highlight the role of rapid bottom-up oscillatory mechanisms for neural coupling and indicate that behavior-based processes may drive synchrony between two brains during social interactions. PMID:28402479

Visual processing in the central bee brain.

PubMed

Paulk, Angelique C; Dacks, Andrew M; Phillips-Portillo, James; Fellous, Jean-Marc; Gronenberg, Wulfila

2009-08-12

Visual scenes comprise enormous amounts of information from which nervous systems extract behaviorally relevant cues. In most model systems, little is known about the transformation of visual information as it occurs along visual pathways. We examined how visual information is transformed physiologically as it is communicated from the eye to higher-order brain centers using bumblebees, which are known for their visual capabilities. We recorded intracellularly in vivo from 30 neurons in the central bumblebee brain (the lateral protocerebrum) and compared these neurons to 132 neurons from more distal areas along the visual pathway, namely the medulla and the lobula. In these three brain regions (medulla, lobula, and central brain), we examined correlations between the neurons' branching patterns and their responses primarily to color, but also to motion stimuli. Visual neurons projecting to the anterior central brain were generally color sensitive, while neurons projecting to the posterior central brain were predominantly motion sensitive. The temporal response properties differed significantly between these areas, with an increase in spike time precision across trials and a decrease in average reliable spiking as visual information processing progressed from the periphery to the central brain. These data suggest that neurons along the visual pathway to the central brain not only are segregated with regard to the physical features of the stimuli (e.g., color and motion), but also differ in the way they encode stimuli, possibly to allow for efficient parallel processing to occur.

A high-resolution 7-Tesla fMRI dataset from complex natural stimulation with an audio movie.

PubMed

Hanke, Michael; Baumgartner, Florian J; Ibe, Pierre; Kaule, Falko R; Pollmann, Stefan; Speck, Oliver; Zinke, Wolf; Stadler, Jörg

2014-01-01

Here we present a high-resolution functional magnetic resonance (fMRI) dataset - 20 participants recorded at high field strength (7 Tesla) during prolonged stimulation with an auditory feature film ("Forrest Gump"). In addition, a comprehensive set of auxiliary data (T1w, T2w, DTI, susceptibility-weighted image, angiography) as well as measurements to assess technical and physiological noise components have been acquired. An initial analysis confirms that these data can be used to study common and idiosyncratic brain response patterns to complex auditory stimulation. Among the potential uses of this dataset are the study of auditory attention and cognition, language and music perception, and social perception. The auxiliary measurements enable a large variety of additional analysis strategies that relate functional response patterns to structural properties of the brain. Alongside the acquired data, we provide source code and detailed information on all employed procedures - from stimulus creation to data analysis. In order to facilitate replicative and derived works, only free and open-source software was utilized.

An Animal Model for Collective Behavior in Humans: The Impact of Manipulated Trust and Aggression

DTIC Science & Technology

2014-04-30

grouped with males compared with females grouped with females. This raises the issue of the reciprocal impact of gender on the response to owl attack...337–342 Ecksteina MP, Dasa K, Phama BT, Petersona MF, Abbeya CK, Sya JL, Giesbrechta B (2012) Neural decoding of collective wisdom with multi- brain ...spiny mice flee in alternating patterns. Behav Brain Res 155:207–216 Eilam D (2003) Open-field behavior withstands drastic changes in arena size. Behav

Pseudo-polar drive patterns for brain electrical impedance tomography.

PubMed

Shi, Xuetao; Dong, Xiuzhen; Shuai, Wanjun; You, Fusheng; Fu, Feng; Liu, Ruigang

2006-11-01

Brain electrical impedance tomography (EIT) is a difficult task as brain tissues are enclosed by the skull of high resistance and cerebrospinal fluid (CSF) of low resistance, which makes internal resistivity information more difficult to extract. In order to seek a single source drive pattern that is more suitable for brain EIT, we built a more realistic experimental setting that simulates a head with the resistivity of the scalp, skull, CSF and brain, and compared the performance of adjacent, cross, polar and pseudo-polar drive patterns in terms of the boundary voltage dynamic range, independent measurement number, total boundary voltage changes and anti-noise performance based on it. The results demonstrate that the pseudo-polar drive pattern is optimal in all the aspects except for the dynamic range. The polar and cross drive patterns come next, and the adjacent drive pattern is the worst. Therefore, the pseudo-polar drive pattern should be chosen for brain EIT.

Pattern Analyses Reveal Separate Experience-Based Fear Memories in the Human Right Amygdala.

PubMed

Braem, Senne; De Houwer, Jan; Demanet, Jelle; Yuen, Kenneth S L; Kalisch, Raffael; Brass, Marcel

2017-08-23

Learning fear via the experience of contingencies between a conditioned stimulus (CS) and an aversive unconditioned stimulus (US) is often assumed to be fundamentally different from learning fear via instructions. An open question is whether fear-related brain areas respond differently to experienced CS-US contingencies than to merely instructed CS-US contingencies. Here, we contrasted two experimental conditions where subjects were instructed to expect the same CS-US contingencies while only one condition was characterized by prior experience with the CS-US contingency. Using multivoxel pattern analysis of fMRI data, we found CS-related neural activation patterns in the right amygdala (but not in other fear-related regions) that dissociated between whether a CS-US contingency had been instructed and experienced versus merely instructed. A second experiment further corroborated this finding by showing a category-independent neural response to instructed and experienced, but not merely instructed, CS presentations in the human right amygdala. Together, these findings are in line with previous studies showing that verbal fear instructions have a strong impact on both brain and behavior. However, even in the face of fear instructions, the human right amygdala still shows a separable neural pattern response to experience-based fear contingencies. SIGNIFICANCE STATEMENT In our study, we addressed a fundamental problem of the science of human fear learning and memory, namely whether fear learning via experience in humans relies on a neural pathway that can be separated from fear learning via verbal information. Using two new procedures and recent advances in the analysis of brain imaging data, we localized purely experience-based fear processing and memory in the right amygdala, thereby making a direct link between human and animal research. Copyright © 2017 the authors 0270-6474/17/378116-15$15.00/0.

Analysis for Distinctive Activation Patterns of Pain and Itchy in the Human Brain Cortex Measured Using Near Infrared Spectroscopy (NIRS)

PubMed Central

Kataoka, Aiko; Kudo, Ayako; Fujino, Fukue; Chen, Yu-Wen; Mitsuyama, Yuki; Nomura, Shinobu; Yoshioka, Tohru

2013-01-01

Pain and itch are closely related sensations, yet qualitatively quite distinct. Despite recent advances in brain imaging techniques, identifying the differences between pain and itch signals in the brain cortex is difficult due to continuous temporal and spatial changes in the signals. The high spatial resolution of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) has substantially advanced research of pain and itch, but these are uncomfortable because of expensiveness, importability and the limited operation in the shielded room. Here, we used near infrared spectroscopy (NIRS), which has more conventional usability. NIRS can be used to visualize dynamic changes in oxygenated hemoglobin and deoxyhemoglobin concentrations in the capillary networks near activated neural circuits in real-time as well as fMRI. We observed distinct activation patterns in the frontal cortex for acute pain and histamine-induced itch. The prefrontal cortex exhibited a pain-related and itch-related activation pattern of blood flow in each subject. Although it looked as though that activation pattern for pain and itching was different in each subject, further cross correlation analysis of NIRS signals between each channels showed an overall agreement with regard to prefrontal area involvement. As a result, pain-related and itch-related blood flow responses (delayed responses in prefrontal area) were found to be clearly different between pain (τ = +18.7 sec) and itch (τ = +0.63 sec) stimulation. This is the first pilot study to demonstrate the temporal and spatial separation of a pain-induced blood flow and an itch-induced blood flow in human cortex during information processing. PMID:24098378

Engaged listeners: shared neural processing of powerful political speeches.

PubMed

Schmälzle, Ralf; Häcker, Frank E K; Honey, Christopher J; Hasson, Uri

2015-08-01

Powerful speeches can captivate audiences, whereas weaker speeches fail to engage their listeners. What is happening in the brains of a captivated audience? Here, we assess audience-wide functional brain dynamics during listening to speeches of varying rhetorical quality. The speeches were given by German politicians and evaluated as rhetorically powerful or weak. Listening to each of the speeches induced similar neural response time courses, as measured by inter-subject correlation analysis, in widespread brain regions involved in spoken language processing. Crucially, alignment of the time course across listeners was stronger for rhetorically powerful speeches, especially for bilateral regions of the superior temporal gyri and medial prefrontal cortex. Thus, during powerful speeches, listeners as a group are more coupled to each other, suggesting that powerful speeches are more potent in taking control of the listeners' brain responses. Weaker speeches were processed more heterogeneously, although they still prompted substantially correlated responses. These patterns of coupled neural responses bear resemblance to metaphors of resonance, which are often invoked in discussions of speech impact, and contribute to the literature on auditory attention under natural circumstances. Overall, this approach opens up possibilities for research on the neural mechanisms mediating the reception of entertaining or persuasive messages. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

What's parenting got to do with it: emotional autonomy and brain and behavioral responses to emotional conflict in children and adolescents.

PubMed

Marusak, Hilary A; Thomason, Moriah E; Sala-Hamrick, Kelsey; Crespo, Laura; Rabinak, Christine A

2017-09-15

Healthy parenting may be protective against the development of emotional psychopathology, particularly for children reared in stressful environments. Little is known, however, about the brain and behavioral mechanisms underlying this association, particularly during childhood and adolescence, when emotional disorders frequently emerge. Here, we demonstrate that psychological control, a parenting strategy known to limit socioemotional development in children, is associated with altered brain and behavioral responses to emotional conflict in 27 at-risk (urban, lower income) youth, ages 9-16. In particular, youth reporting higher parental psychological control demonstrated lower activity in the left anterior insula, a brain area involved in emotion conflict processing, and submitted faster but less accurate behavioral responses-possibly reflecting an avoidant pattern. Effects were not replicated for parental care, and did not generalize to an analogous nonemotional conflict task. We also find evidence that behavioral responses to emotional conflict bridge the previously reported link between parental overcontrol and anxiety in children. Effects of psychological control may reflect a parenting style that limits opportunities to practice self-regulation when faced with emotionally charged situations. Results support the notion that parenting strategies that facilitate appropriate amounts of socioemotional competence and autonomy in children may be protective against social and emotional difficulties. © 2017 John Wiley & Sons Ltd.

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

PubMed Central

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

2014-01-01

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

Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain

PubMed Central

Auger, Catherine J.; Coss, Dylan; Auger, Anthony P.; Forbes-Lorman, Robin M.

2011-01-01

Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor α (ERα) mRNA expression and decreased ERα promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. The maintenance of methylated or demethylated states of some genes in the adult brain by the presence of steroid hormones may play a role in the homeostatic regulation of behaviorally relevant systems. PMID:21368111

Patterns of relapse in primary central nervous system lymphoma: inferences regarding the role of the neuro-vascular unit and monoclonal antibodies in treating occult CNS disease.

PubMed

Ambady, Prakash; Fu, Rongwei; Netto, Joao Prola; Kersch, Cymon; Firkins, Jenny; Doolittle, Nancy D; Neuwelt, Edward A

2017-06-02

The radiologic features and patterns of primary central nervous system lymphoma (PCNSL) at initial presentation are well described. High response rates can be achieved with first-line high-dose methotrexate (HD-MTX) based regimens, yet many relapse within 2 years of diagnosis. We describe the pattern of relapse and review the potential mechanisms involved in relapse. We identified 78 consecutive patients who attained complete radiographic response (CR) during or after first-line treatment for newly diagnosed PCNSL (CD20+, diffuse large B cell type). Patients were treated with HD-MTX based regimen in conjunction with blood-brain barrier disruption (HD-MTX/BBBD); 44 subsequently relapsed. Images and medical records of these 44 consecutive patients were retrospectively reviewed. The anatomical location of enhancing lesions at initial diagnosis and at the time of relapse were identified and compared. 37/44 patients fulfilled inclusion criteria and had new measureable enhancing lesions at relapse; the pattern and location of relapse of these 37 patients were identified. At relapse, the new enhancement was at a spatially distinct site in 30 of 37 patients. Local relapse was found only in seven patients. Unlike gliomas, the majority of PCNSL had radiographic relapse at spatially distinct anatomical locations within the brain behind a previously intact neurovascular unit (NVU), and in few cases outside, the central nervous system (CNS). This may suggest either (1) reactivation of occult reservoirs behind an intact NVU in the CNS (or ocular) or (2) seeding from bone marrow or other extra CNS sites. Recognizing patterns of relapse is key for early detection and may provide insight into potential mechanisms of relapse as well as help develop strategies to extend duration of complete response.

On the Pressure Response in the Brain due to Short Duration Blunt Impacts

PubMed Central

Pearce, Christopher W.; Young, Philippe G.

2014-01-01

When the head is subject to non-penetrating (blunt) impact, contusion-type injuries are commonly identified beneath the impact site (the coup) and, in some instances, at the opposite pole (the contre-coup). This pattern of injury has long eluded satisfactory explanation and blunt head injury mechanisms in general remain poorly understood. There are only a small number of studies in the open literature investigating the head's response to short duration impacts, which can occur in collisions with light projectiles. As such, the head impact literature to date has focussed almost exclusively on impact scenarios which lead to a quasi-static pressure response in the brain. In order to investigate the response of the head to a wide range of impact durations, parametric numerical studies were performed on a highly bio-fidelic finite element model of the human head created from in vivo magnetic resonance imaging (MRI) scan data with non-linear tissue material properties. We demonstrate that short duration head impacts can lead to potentially deleterious transients of positive and negative intra-cranial pressure over an order of magnitude larger than those observed in the quasi-static regime despite reduced impact force and energy. The onset of this phenomenon is shown to be effectively predicted by the ratio of impact duration to the period of oscillation of the first ovalling mode of the system. These findings point to dramatically different pressure distributions in the brain and hence different patterns of injury depending on projectile mass, and provide a potential explanation for dual coup/contre-coup injuries observed clinically. PMID:25478695

On the pressure response in the brain due to short duration blunt impacts.

PubMed

Pearce, Christopher W; Young, Philippe G

2014-01-01

When the head is subject to non-penetrating (blunt) impact, contusion-type injuries are commonly identified beneath the impact site (the coup) and, in some instances, at the opposite pole (the contre-coup). This pattern of injury has long eluded satisfactory explanation and blunt head injury mechanisms in general remain poorly understood. There are only a small number of studies in the open literature investigating the head's response to short duration impacts, which can occur in collisions with light projectiles. As such, the head impact literature to date has focussed almost exclusively on impact scenarios which lead to a quasi-static pressure response in the brain. In order to investigate the response of the head to a wide range of impact durations, parametric numerical studies were performed on a highly bio-fidelic finite element model of the human head created from in vivo magnetic resonance imaging (MRI) scan data with non-linear tissue material properties. We demonstrate that short duration head impacts can lead to potentially deleterious transients of positive and negative intra-cranial pressure over an order of magnitude larger than those observed in the quasi-static regime despite reduced impact force and energy. The onset of this phenomenon is shown to be effectively predicted by the ratio of impact duration to the period of oscillation of the first ovalling mode of the system. These findings point to dramatically different pressure distributions in the brain and hence different patterns of injury depending on projectile mass, and provide a potential explanation for dual coup/contre-coup injuries observed clinically.

Past tense in the brain's time: neurophysiological evidence for dual-route processing of past-tense verbs.

PubMed

Bakker, Iske; Macgregor, Lucy J; Pulvermüller, Friedemann; Shtyrov, Yury

2013-05-01

A controversial issue in neuro- and psycholinguistics is whether regular past-tense forms of verbs are stored lexically or generated productively by the application of abstract combinatorial schemas, for example affixation rules. The success or failure of models in accounting for this particular issue can be used to draw more general conclusions about cognition and the degree to which abstract, symbolic representations and rules are psychologically and neurobiologically real. This debate can potentially be resolved using a neurophysiological paradigm, in which alternative predictions of the brain response patterns for lexical and syntactic processing are put to the test. We used magnetoencephalography (MEG) to record neural responses to spoken monomorphemic words ('hide'), pseudowords ('smide'), regular past-tense forms ('cried') and ungrammatical (overregularised) past-tense forms ('flied') in a passive listening oddball paradigm, in which lexically and syntactically modulated stimuli are known to elicit distinct patterns of the mismatch negativity (MMN) brain response. We observed an enhanced ('lexical') MMN to monomorphemic words relative to pseudowords, but a reversed ('syntactic') MMN to ungrammatically inflected past tenses relative to grammatical forms. This dissociation between responses to monomorphemic and bimorphemic stimuli indicates that regular past tenses are processed more similarly to syntactic sequences than to lexically stored monomorphemic words, suggesting that regular past tenses are generated productively by the application of a combinatorial scheme to their separately represented stems and affixes. We suggest discrete combinatorial neuronal assemblies, which bind classes of sequentially occurring lexical elements into morphologically complex units, as the neurobiological basis of regular past tense inflection. Copyright © 2013 Elsevier Inc. All rights reserved.

Spectral properties of identified polarized-light sensitive interneurons in the brain of the desert locust Schistocerca gregaria.

PubMed

Kinoshita, Michiyo; Pfeiffer, Keram; Homberg, Uwe

2007-04-01

Many migrating animals employ a celestial compass mechanism for spatial navigation. Behavioral experiments in bees and ants have shown that sun compass navigation may rely on the spectral gradient in the sky as well as on the pattern of sky polarization. While polarized-light sensitive interneurons (POL neurons) have been identified in the brain of several insect species, there are at present no data on the neural basis of coding the spectral gradient of the sky. In the present study we have analyzed the chromatic properties of two identified POL neurons in the brain of the desert locust. Both neurons, termed TuTu1 and LoTu1, arborize in the anterior optic tubercle and respond to unpolarized light as well as to polarized light. We show here that the polarized-light response of both types of neuron relies on blue-sensitive photoreceptors. Responses to unpolarized light depended on stimulus position and wavelength. Dorsal unpolarized blue light inhibited the neurons, while stimulation from the ipsilateral side resulted in opponent responses to UV light and green light. While LoTu1 was inhibited by UV light and was excited by green light, one subtype of TuTu1 was excited by UV and inhibited by green light. In LoTu1 the sensitivity to polarized light was at least 2 log units higher than the response to unpolarized light stimuli. Taken together, the spatial and chromatic properties of the neurons may be suited to signal azimuthal directions based on a combination of the spectral gradient and the polarization pattern of the sky.

Pattern of brain injury and depressed heart rate variability in newborns with hypoxic ischemic encephalopathy.

PubMed

Metzler, Marina; Govindan, Rathinaswamy; Al-Shargabi, Tareq; Vezina, Gilbert; Andescavage, Nickie; Wang, Yunfei; du Plessis, Adre; Massaro, An N

2017-09-01

BackgroundDecreased heart rate variability (HRV) is a measure of autonomic dysfunction and brain injury in newborns with hypoxic ischemic encephalopathy (HIE). This study aimed to characterize the relationship between HRV and brain injury pattern using magnetic resonance imaging (MRI) in newborns with HIE undergoing therapeutic hypothermia.MethodsHRV metrics were quantified in the time domain (α S , α L , and root mean square at short (RMS S ) and long (RMS L ) timescales) and frequency domain (relative low-(LF) and high-frequency (HF) power) over 24-27 h of life. The brain injury pattern shown by MRI was classified as no injury, pure cortical/white matter injury, mixed watershed/mild basal ganglia injury, predominant basal ganglia or global injury, and death. HRV metrics were compared across brain injury pattern groups using a random-effects mixed model.ResultsData from 74 infants were analyzed. Brain injury pattern was significantly associated with the degree of HRV suppression. Specifically, negative associations were observed between the pattern of brain injury and RMS S (estimate -0.224, SE 0.082, P=0.006), RMS L (estimate -0.189, SE 0.082, P=0.021), and LF power (estimate -0.044, SE 0.016, P=0.006).ConclusionDegree of HRV depression is related to the pattern of brain injury. HRV monitoring may provide insights into the pattern of brain injury at the bedside.

PATTERN OF BRAIN INJURY AND DEPRESSED HEART RATE VARIABILITY IN NEWBORNS WITH HYPOXIC ISCHEMIC ENCEPHALOPATHY

PubMed Central

Metzler, Marina; Govindan, Rathinaswamy; Al-Shargabi, Tareq; Vezina, Gilbert; Andescavage, Nickie; Wang, Yunfei; du Plessis, Adre; Massaro, An N

2017-01-01

Background Decreased heart rate variability (HRV) is a measure of autonomic dysfunction and brain injury in newborns with hypoxic ischemic encephalopathy (HIE). This study aimed to characterize the relationship between HRV and brain injury pattern by MRI in newborns with HIE undergoing therapeutic hypothermia. Methods HRV metrics were quantified in the time domain (αS, αL, and root mean square at short [RMSS] and long [RMSL] time scales) and frequency domain (relative low-[LF] and high-frequency [HF] power) during the time period 24–27 hours of life. Brain injury pattern by MRI was classified as no injury, pure cortical/white matter injury, mixed watershed/mild basal nuclei injury, predominant basal nuclei or global injury, and died. HRV metrics were compared across brain injury pattern groups using a random effects mixed model. Results Data from 74 infants were analyzed. Brain injury pattern was significantly associated with degree of HRV suppression. Specifically, negative associations were observed between pattern of brain injury and RMSS (estimate −0.224, SE 0.082, p=0.006), RMSL (estimate −0.189, SE 0.082, p=0.021), and LF power (estimate −0.044, SE 0.016, p=0.006). Conclusion Degree of HRV depression is related to pattern of brain injury. HRV monitoring may provide insights into pattern of brain injury at the bedside. PMID:28376079

Electroencephalographic responses to ionizing radiation.

PubMed

GARCIA, J; BUCHWALD, N A; BACH-Y-RITA, G; FEDER, B H; KOELLING, R A

1963-04-19

Electroencephalographic recordings made from chronically implanted cortical electrodes indicate that ionizing radiation has an immediate effect upon brain wave patterns. X-rays delivered at the rate of 0.2 roentgen per second produce an arousal effect resembling that which occurs as a result of stimulation through peripheral receptor systems.

Decoding of visual activity patterns from fMRI responses using multivariate pattern analyses and convolutional neural network.

PubMed

Zafar, Raheel; Kamel, Nidal; Naufal, Mohamad; Malik, Aamir Saeed; Dass, Sarat C; Ahmad, Rana Fayyaz; Abdullah, Jafri M; Reza, Faruque

2017-01-01

Decoding of human brain activity has always been a primary goal in neuroscience especially with functional magnetic resonance imaging (fMRI) data. In recent years, Convolutional neural network (CNN) has become a popular method for the extraction of features due to its higher accuracy, however it needs a lot of computation and training data. In this study, an algorithm is developed using Multivariate pattern analysis (MVPA) and modified CNN to decode the behavior of brain for different images with limited data set. Selection of significant features is an important part of fMRI data analysis, since it reduces the computational burden and improves the prediction performance; significant features are selected using t-test. MVPA uses machine learning algorithms to classify different brain states and helps in prediction during the task. General linear model (GLM) is used to find the unknown parameters of every individual voxel and the classification is done using multi-class support vector machine (SVM). MVPA-CNN based proposed algorithm is compared with region of interest (ROI) based method and MVPA based estimated values. The proposed method showed better overall accuracy (68.6%) compared to ROI (61.88%) and estimation values (64.17%).

Spatiotemporal patterns of ERP based on combined ICA-LORETA analysis

NASA Astrophysics Data System (ADS)

Zhang, Jiacai; Guo, Taomei; Xu, Yaqin; Zhao, Xiaojie; Yao, Li

2007-03-01

In contrast to the FMRI methods widely used up to now, this method try to understand more profoundly how the brain systems work under sentence processing task map accurately the spatiotemporal patterns of activity of the large neuronal populations in the human brain from the analysis of ERP data recorded on the brain scalp. In this study, an event-related brain potential (ERP) paradigm to record the on-line responses to the processing of sentences is chosen as an example. In order to give attention to both utilizing the ERPs' temporal resolution of milliseconds and overcoming the insensibility of cerebral location ERP sources, we separate these sources in space and time based on a combined method of independent component analysis (ICA) and low-resolution tomography (LORETA) algorithms. ICA blindly separate the input ERP data into a sum of temporally independent and spatially fixed components arising from distinct or overlapping brain or extra-brain sources. And then the spatial maps associated with each ICA component are analyzed, with use of LORETA to uniquely locate its cerebral sources throughout the full brain according to the assumption that neighboring neurons are simultaneously and synchronously activated. Our results show that the cerebral computation mechanism underlies content words reading is mediated by the orchestrated activity of several spatially distributed brain sources located in the temporal, frontal, and parietal areas, and activate at distinct time intervals and are grouped into different statistically independent components. Thus ICA-LORETA analysis provides an encouraging and effective method to study brain dynamics from ERP.

Resolving human object recognition in space and time

PubMed Central

Cichy, Radoslaw Martin; Pantazis, Dimitrios; Oliva, Aude

2014-01-01

A comprehensive picture of object processing in the human brain requires combining both spatial and temporal information about brain activity. Here, we acquired human magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) responses to 92 object images. Multivariate pattern classification applied to MEG revealed the time course of object processing: whereas individual images were discriminated by visual representations early, ordinate and superordinate category levels emerged relatively later. Using representational similarity analysis, we combine human fMRI and MEG to show content-specific correspondence between early MEG responses and primary visual cortex (V1), and later MEG responses and inferior temporal (IT) cortex. We identified transient and persistent neural activities during object processing, with sources in V1 and IT., Finally, human MEG signals were correlated to single-unit responses in monkey IT. Together, our findings provide an integrated space- and time-resolved view of human object categorization during the first few hundred milliseconds of vision. PMID:24464044

Neural correlates of moral judgment in pedophilia.

PubMed

Massau, Claudia; Kärgel, Christian; Weiß, Simone; Walter, Martin; Ponseti, Jorge; Hc Krueger, Tillmann; Walter, Henrik; Schiffer, Boris

2017-09-01

Pedophilia is a sexual preference that is often associated with child sex offending (CSO). Sexual urges towards prepubescent children and specifically acting upon those urges are universally regarded as immoral. However, up until now, it is completely unknown whether moral processing of sexual offenses is altered in pedophiles. A total of 31 pedophilic men and 19 healthy controls were assessed by using functional magnetic resonance imaging (fMRI) in combination with a moral judgment paradigm consisting of 36 scenarios describing different types of offenses.Scenarios depicting sexual offenses against children compared to those depicting adults were associated with higher pattern of activation in the left temporo-parietal-junction (TPJ) and left posterior insular cortex, the posterior cingulate gyrus as well as the precuneus in controls relative to pedophiles, and vice versa. Moreover, brain activation in these areas were positively associated with ratings of moral reprehensibility and negatively associated with decision durations, but only in controls. Brain activation, found in key areas related to the broad network of moral judgment, theory of mind and (socio-)moral disgust - point to different moral processing of sexual offenses in pedophilia in general. The lack of associations between brain activation and behavioral responses in pedophiles further suggest a biased response pattern or dissected implicit valuation processes. © The Author (2017). Published by Oxford University Press.

Neural correlates of moral judgment in pedophilia

PubMed Central

Kärgel, Christian; Weiß, Simone; Walter, Martin; Ponseti, Jorge; HC Krueger, Tillmann; Walter, Henrik; Schiffer, Boris

2017-01-01

Abstract Pedophilia is a sexual preference that is often associated with child sex offending (CSO). Sexual urges towards prepubescent children and specifically acting upon those urges are universally regarded as immoral. However, up until now, it is completely unknown whether moral processing of sexual offenses is altered in pedophiles. A total of 31 pedophilic men and 19 healthy controls were assessed by using functional magnetic resonance imaging (fMRI) in combination with a moral judgment paradigm consisting of 36 scenarios describing different types of offenses. Scenarios depicting sexual offenses against children compared to those depicting adults were associated with higher pattern of activation in the left temporo-parietal-junction (TPJ) and left posterior insular cortex, the posterior cingulate gyrus as well as the precuneus in controls relative to pedophiles, and vice versa. Moreover, brain activation in these areas were positively associated with ratings of moral reprehensibility and negatively associated with decision durations, but only in controls. Brain activation, found in key areas related to the broad network of moral judgment, theory of mind and (socio-)moral disgust - point to different moral processing of sexual offenses in pedophilia in general. The lack of associations between brain activation and behavioral responses in pedophiles further suggest a biased response pattern or dissected implicit valuation processes. PMID:28992273

MSG-Evoked c-Fos Activity in the Nucleus of the Solitary Tract Is Dependent upon Fluid Delivery and Stimulation Parameters

PubMed Central

Thompson, John A.

2016-01-01

The marker of neuronal activation, c-Fos, can be used to visualize spatial patterns of neural activity in response to taste stimulation. Because animals will not voluntarily consume aversive tastes, these stimuli are infused directly into the oral cavity via intraoral cannulae, whereas appetitive stimuli are given in drinking bottles. Differences in these 2 methods make comparison of taste-evoked brain activity between results that utilize these methods problematic. Surprisingly, the intraoral cannulae experimental conditions that produce a similar pattern of c-Fos activity in response to taste stimulation remain unexplored. Stimulation pattern (e.g., constant/intermittent) and hydration state (e.g., water-restricted/hydrated) are the 2 primary differences between delivering tastes via bottles versus intraoral cannulae. Thus, we quantified monosodium glutamate (MSG)-evoked brain activity, as measured by c-Fos, in the nucleus of the solitary tract (nTS; primary taste nucleus) across several conditions. The number and pattern of c-Fos neurons in the nTS of animals that were water-restricted and received a constant infusion of MSG via intraoral cannula most closely mimicked animals that consumed MSG from a bottle. Therefore, in order to compare c-Fos activity between cannulae-stimulated and bottle-stimulated animals, cannulated animals should be water restricted prior to stimulation, and receive taste stimuli at a constant flow. PMID:26762887

Patient classification as an outlier detection problem: An application of the One-Class Support Vector Machine

PubMed Central

Mourão-Miranda, Janaina; Hardoon, David R.; Hahn, Tim; Marquand, Andre F.; Williams, Steve C.R.; Shawe-Taylor, John; Brammer, Michael

2011-01-01

Pattern recognition approaches, such as the Support Vector Machine (SVM), have been successfully used to classify groups of individuals based on their patterns of brain activity or structure. However these approaches focus on finding group differences and are not applicable to situations where one is interested in accessing deviations from a specific class or population. In the present work we propose an application of the one-class SVM (OC-SVM) to investigate if patterns of fMRI response to sad facial expressions in depressed patients would be classified as outliers in relation to patterns of healthy control subjects. We defined features based on whole brain voxels and anatomical regions. In both cases we found a significant correlation between the OC-SVM predictions and the patients' Hamilton Rating Scale for Depression (HRSD), i.e. the more depressed the patients were the more of an outlier they were. In addition the OC-SVM split the patient groups into two subgroups whose membership was associated with future response to treatment. When applied to region-based features the OC-SVM classified 52% of patients as outliers. However among the patients classified as outliers 70% did not respond to treatment and among those classified as non-outliers 89% responded to treatment. In addition 89% of the healthy controls were classified as non-outliers. PMID:21723950

Food-induced brain responses and eating behaviour.

PubMed

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

2012-11-01

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

The burden of conscientiousness? Examining brain activation and cortisol response during social evaluative stress.

PubMed

Dahm, Anne-Sophie; Schmierer, Phöbe; Veer, Ilya M; Streit, Fabian; Görgen, Anna; Kruschwitz, Johann; Wüst, Stefan; Kirsch, Peter; Walter, Henrik; Erk, Susanne

2017-04-01

Although conscientiousness has for a long time been considered generally adaptive, there are findings challenging this view, suggesting that conscientiousness might be less advantageous during uncontrollable stress. We here examined the impact of conscientiousness on brain activation during and the cortisol response following an uncontrollable social evaluative stress task in order to test this hypothesis. Brain activation and cortisol levels were measured during an fMRI stress task, where subjects (n=86) performed cognitive tasks containing preprogrammed failure under time pressure, while being monitored by a panel of experts inducing social-evaluative threat. The degree of conscientiousness was measured using the NEO-FFI. We observed a positive correlation between conscientiousness and salivary cortisol levels in response to the stressful task in male subjects only. In male subjects conscientiousness correlated positively with activation in right amygdala and left insula, and, moreover, mediated the influence of amygdala and insula activation on cortisol output. This pattern of brain activation can be interpreted as a disadvantageous response to uncontrollable stress to which highly conscientious individuals might be predisposed. This is the first study showing the effect of conscientiousness on physiology and brain activation to an uncontrollable psychosocial stressor. Our results provide neurobiological evidence for the hypothesis that conscientiousness should not just be seen as beneficial, but rather as a trait associated with either costs or benefits depending on the extent to which one is in control of the situation. Copyright © 2017 Elsevier Ltd. All rights reserved.

A target sample of adolescents and reward processing: same neural and behavioral correlates engaged in common paradigms?

PubMed

Nees, Frauke; Vollstädt-Klein, Sabine; Fauth-Bühler, Mira; Steiner, Sabina; Mann, Karl; Poustka, Luise; Banaschewski, Tobias; Büchel, Christian; Conrod, Patricia J; Garavan, Hugh; Heinz, Andreas; Ittermann, Bernd; Artiges, Eric; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Smolka, Michael N; Struve, Maren; Loth, Eva; Schumann, Gunter; Flor, Herta

2012-11-01

Adolescence is a transition period that is assumed to be characterized by increased sensitivity to reward. While there is growing research on reward processing in adolescents, investigations into the engagement of brain regions under different reward-related conditions in one sample of healthy adolescents, especially in a target age group, are missing. We aimed to identify brain regions preferentially activated in a reaction time task (monetary incentive delay (MID) task) and a simple guessing task (SGT) in a sample of 14-year-old adolescents (N = 54) using two commonly used reward paradigms. Functional magnetic resonance imaging was employed during the MID with big versus small versus no win conditions and the SGT with big versus small win and big versus small loss conditions. Analyses focused on changes in blood oxygen level-dependent contrasts during reward and punishment processing in anticipation and feedback phases. We found clear magnitude-sensitive response in reward-related brain regions such as the ventral striatum during anticipation in the MID task, but not in the SGT. This was also true for reaction times. The feedback phase showed clear reward-related, but magnitude-independent, response patterns, for example in the anterior cingulate cortex, in both tasks. Our findings highlight neural and behavioral response patterns engaged in two different reward paradigms in one sample of 14-year-old healthy adolescents and might be important for reference in future studies investigating reward and punishment processing in a target age group.

Dopamine reward prediction-error signalling: a two-component response

PubMed Central

Schultz, Wolfram

2017-01-01

Environmental stimuli and objects, including rewards, are often processed sequentially in the brain. Recent work suggests that the phasic dopamine reward prediction-error response follows a similar sequential pattern. An initial brief, unselective and highly sensitive increase in activity unspecifically detects a wide range of environmental stimuli, then quickly evolves into the main response component, which reflects subjective reward value and utility. This temporal evolution allows the dopamine reward prediction-error signal to optimally combine speed and accuracy. PMID:26865020

A Comparison of Independent Event-Related Desynchronization Responses in Motor-Related Brain Areas to Movement Execution, Movement Imagery, and Movement Observation.

PubMed

Duann, Jeng-Ren; Chiou, Jin-Chern

2016-01-01

Electroencephalographic (EEG) event-related desynchronization (ERD) induced by movement imagery or by observing biological movements performed by someone else has recently been used extensively for brain-computer interface-based applications, such as applications used in stroke rehabilitation training and motor skill learning. However, the ERD responses induced by the movement imagery and observation might not be as reliable as the ERD responses induced by movement execution. Given that studies on the reliability of the EEG ERD responses induced by these activities are still lacking, here we conducted an EEG experiment with movement imagery, movement observation, and movement execution, performed multiple times each in a pseudorandomized order in the same experimental runs. Then, independent component analysis (ICA) was applied to the EEG data to find the common motor-related EEG source activity shared by the three motor tasks. Finally, conditional EEG ERD responses associated with the three movement conditions were computed and compared. Among the three motor conditions, the EEG ERD responses induced by motor execution revealed the alpha power suppression with highest strengths and longest durations. The ERD responses of the movement imagery and movement observation only partially resembled the ERD pattern of the movement execution condition, with slightly better detectability for the ERD responses associated with the movement imagery and faster ERD responses for movement observation. This may indicate different levels of involvement in the same motor-related brain circuits during different movement conditions. In addition, because the resulting conditional EEG ERD responses from the ICA preprocessing came with minimal contamination from the non-related and/or artifactual noisy components, this result can play a role of the reference for devising a brain-computer interface using the EEG ERD features of movement imagery or observation.

Neural Correlates and Connectivity underlying Stress-related Impulse Control Difficulties in Alcoholism

PubMed Central

Seo, Dongju; Lacadie, Cheryl M.; Sinha, Rajita

2016-01-01

BACKGROUND Stress triggers impulsive and addictive behaviors, and alcoholism has been frequently associated with increased stress sensitivity and impulse control problems. However, neural correlates underlying the link between alcoholism and impulsivity in the context of stress in patients with alcohol use disorders (AUD) have not been well studied. METHOD The current study investigated neural correlates and connectivity patterns associated with impulse control difficulties in abstinent AUD patients. Using functional magnetic resonance imaging, brain responses of 37 AUD inpatients and 37 demographically-matched healthy controls were examined during brief individualized imagery trials of stress, alcohol-cue and neutral-relaxing conditions. Stress-related impulsivity was measured using a subscale score of impulse control problems from Difficulties in Emotion Regulation Scale (DERS). RESULTS Impulse control difficulties in AUD patients were significantly associated with hypoactive response to stress in the ventromedial prefrontal cortex (VmPFC), right caudate, and left lateral PFC (LPFC) compared to the neutral condition (p<0.01, whole-brain corrected). These regions were used as seed regions to further examine the connectivity patterns with other brain regions. With the VmPFC seed, AUD patients showed reduced connectivity with the anterior cingulate cortex (ACC) compared to controls, which are core regions of emotion regulation, suggesting AUD patients’ decreased ability to modulate emotional response under distressed state. With the right caudate seed, patients showed increased connectivity with the right motor cortex, suggesting increased tendency toward habitually driven behaviors. With the left LPFC seed, decreased connectivity with the dorsomedial PFC (DmPFC), but increased connectivity with sensory and motor cortices were found in AUD patients compared to controls (p<0.05, whole-brain corrected). Reduced connectivity between the left LPFC and DmPFC was further associated with increased stress-induced anxiety in AUD patients (p<0.05, with adjusted Bonferroni correction). CONCLUSION Hypoactive response to stress and altered connectivity in key emotion regulatory regions may account for greater stress-related impulse control problems in alcoholism. PMID:27501356

Neural Correlates and Connectivity Underlying Stress-Related Impulse Control Difficulties in Alcoholism.

PubMed

Seo, Dongju; Lacadie, Cheryl M; Sinha, Rajita

2016-09-01

Stress triggers impulsive and addictive behaviors, and alcoholism has been frequently associated with increased stress sensitivity and impulse control problems. However, neural correlates underlying the link between alcoholism and impulsivity in the context of stress in patients with alcohol use disorders (AUD) have not been well studied. This study investigated neural correlates and connectivity patterns associated with impulse control difficulties in abstinent AUD patients. Using functional magnetic resonance imaging, brain responses of 37 AUD inpatients, and 37 demographically matched healthy controls were examined during brief individualized imagery trials of stress, alcohol cue, and neutral-relaxing conditions. Stress-related impulsivity was measured using a subscale score of impulse control problems from Difficulties in Emotion Regulation Scale. Impulse control difficulties in AUD patients were significantly associated with hypo-active response to stress in the ventromedial prefrontal cortex (VmPFC), right caudate, and left lateral PFC (LPFC) compared to the neutral condition (p < 0.01, whole-brain corrected). These regions were used as seed regions to further examine the connectivity patterns with other brain regions. With the VmPFC seed, AUD patients showed reduced connectivity with the anterior cingulate cortex compared to controls, which are core regions of emotion regulation, suggesting AUD patients' decreased ability to modulate emotional response under distressed state. With the right caudate seed, patients showed increased connectivity with the right motor cortex, suggesting increased tendency toward habitually driven behaviors. With the left LPFC seed, decreased connectivity with the dorsomedial PFC (DmPFC), but increased connectivity with sensory and motor cortices were found in AUD patients compared to controls (p < 0.05, whole-brain corrected). Reduced connectivity between the left LPFC and DmPFC was further associated with increased stress-induced anxiety in AUD patients (p < 0.05, with adjusted Bonferroni correction). Hypo-active response to stress and altered connectivity in key emotion regulatory regions may account for greater stress-related impulse control problems in alcoholism. Copyright © 2016 by the Research Society on Alcoholism.

Tracing Activity Across the Whole Brain Neural Network with Optogenetic Functional Magnetic Resonance Imaging

PubMed Central

Lee, Jin Hyung

2011-01-01

Despite the overwhelming need, there has been a relatively large gap in our ability to trace network level activity across the brain. The complex dense wiring of the brain makes it extremely challenging to understand cell-type specific activity and their communication beyond a few synapses. Recent development of the optogenetic functional magnetic resonance imaging (ofMRI) provides a new impetus for the study of brain circuits by enabling causal tracing of activities arising from defined cell types and firing patterns across the whole brain. Brain circuit elements can be selectively triggered based on their genetic identity, cell body location, and/or their axonal projection target with temporal precision while the resulting network response is monitored non-invasively with unprecedented spatial and temporal accuracy. With further studies including technological innovations to bring ofMRI to its full potential, ofMRI is expected to play an important role in our system-level understanding of the brain circuit mechanism. PMID:22046160

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

PubMed

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

2008-02-01

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

Predictive information processing is a fundamental learning mechanism present in early development: evidence from infants.

PubMed

Trainor, Laurel J

2012-02-01

Evidence is presented that predictive coding is fundamental to brain function and present in early infancy. Indeed, mismatch responses to unexpected auditory stimuli are among the earliest robust cortical event-related potential responses, and have been measured in young infants in response to many types of deviation, including in pitch, timing, and melodic pattern. Furthermore, mismatch responses change quickly with specific experience, suggesting that predictive coding reflects a powerful, early-developing learning mechanism. Copyright © 2011 Elsevier B.V. All rights reserved.

The neural correlates of moral decision-making: A systematic review and meta-analysis of moral evaluations and response decision judgements.

PubMed

Garrigan, Beverley; Adlam, Anna L R; Langdon, Peter E

2016-10-01

The aims of this systematic review were to determine: (a) which brain areas are consistently more active when making (i) moral response decisions, defined as choosing a response to a moral dilemma, or deciding whether to accept a proposed solution, or (ii) moral evaluations, defined as judging the appropriateness of another's actions in a moral dilemma, rating moral statements as right or wrong, or identifying important moral issues; and (b) shared and significantly different activation patterns for these two types of moral judgements. A systematic search of the literature returned 28 experiments. Activation likelihood estimate analysis identified the brain areas commonly more active for moral response decisions and for moral evaluations. Conjunction analysis revealed shared activation for both types of moral judgement in the left middle temporal gyrus, cingulate gyrus, and medial frontal gyrus. Contrast analyses found no significant clusters of increased activation for the moral evaluations-moral response decisions contrast, but found that moral response decisions additionally activated the left and right middle temporal gyrus and the right precuneus. Making one's own moral decisions involves different brain areas compared to judging the moral actions of others, implying that these judgements may involve different processes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Brain activity patterns induced by interrupting the cognitive processes with online advertising.

PubMed

Rejer, Izabela; Jankowski, Jarosław

2017-11-01

As a result of the increasing role of online advertising and strong competition among advertisers, intrusive techniques are commonly used to attract web users' attention. Moreover, since marketing content is usually delivered to the target audience when they are performing typical online tasks, like searching for information or reading online content, its delivery interrupts the web user's current cognitive process. The question posed by many researchers in the field of online advertising is: how should we measure the influence of interruption of cognitive processes on human behavior and emotional state? Much research has been conducted in this field; however, most of this research has focused on monitoring activity in the simulated environment, or processing declarative responses given by users in prepared questionnaires. In this paper, a more direct real-time approach is taken, and the effect of the interruption on a web user is analyzed directly by studying the activity of his brain. This paper presents the results of an experiment that was conducted to find the brain activity patterns associated with interruptions of the cognitive process by showing internet advertisements during a text-reading task. Three specific aspects were addressed in the experiment: individual patterns, the consistency of these patterns across trials, and the intra-subject correlation of the individual patterns. Two main effects were observed for most subjects: a drop in activity in the frontal and prefrontal cortical areas across all frequency bands, and significant changes in the frontal/prefrontal asymmetry index.

A Study of the Response of the Human Cadaver Head to Impact

PubMed Central

Hardy, Warren N.; Mason, Matthew J.; Foster, Craig D.; Shah, Chirag S.; Kopacz, James M.; Yang, King H.; King, Albert I.; Bishop, Jennifer; Bey, Michael; Anderst, William; Tashman, Scott

2008-01-01

High-speed biplane x-ray and neutral density targets were used to examine brain displacement and deformation during impact. Relative motion, maximum principal strain, maximum shear strain, and intracranial pressure were measured in thirty-five impacts using eight human cadaver head and neck specimens. The effect of a helmet was evaluated. During impact, local brain tissue tends to keep its position and shape with respect to the inertial frame, resulting in relative motion between the brain and skull and deformation of the brain. The local brain motions tend to follow looping patterns. Similar patterns are observed for impact in different planes, with some degree of posterior-anterior and right-left symmetry. Peak coup pressure and pressure rate increase with increasing linear acceleration, but coup pressure pulse duration decreases. Peak average maximum principal strain and maximum shear are on the order of 0.09 for CFC 60 Hz data for these tests. Peak average maximum principal strain and maximum shear increase with increasing linear acceleration, coup pressure, and coup pressure rate. Linear and angular acceleration of the head are reduced with use of a helmet, but strain increases. These results can be used for the validation of finite element models of the human head. PMID:18278591

Measuring speaker–listener neural coupling with functional near infrared spectroscopy

PubMed Central

Liu, Yichuan; Piazza, Elise A.; Simony, Erez; Shewokis, Patricia A.; Onaral, Banu; Hasson, Uri; Ayaz, Hasan

2017-01-01

The present study investigates brain-to-brain coupling, defined as inter-subject correlations in the hemodynamic response, during natural verbal communication. We used functional near-infrared spectroscopy (fNIRS) to record brain activity of 3 speakers telling stories and 15 listeners comprehending audio recordings of these stories. Listeners’ brain activity was significantly correlated with speakers’ with a delay. This between-brain correlation disappeared when verbal communication failed. We further compared the fNIRS and functional Magnetic Resonance Imaging (fMRI) recordings of listeners comprehending the same story and found a significant relationship between the fNIRS oxygenated-hemoglobin concentration changes and the fMRI BOLD in brain areas associated with speech comprehension. This correlation between fNIRS and fMRI was only present when data from the same story were compared between the two modalities and vanished when data from different stories were compared; this cross-modality consistency further highlights the reliability of the spatiotemporal brain activation pattern as a measure of story comprehension. Our findings suggest that fNIRS can be used for investigating brain-to-brain coupling during verbal communication in natural settings. PMID:28240295

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

Intersubject synchronisation analysis of brain activity associated with the instant effects of acupuncture: an fMRI study.

PubMed

Jin, Lingmin; Sun, Jinbo; Xu, Ziliang; Yang, Xuejuan; Liu, Peng; Qin, Wei

2018-02-01

To use a promising analytical method, namely intersubject synchronisation (ISS), to evaluate the brain activity associated with the instant effects of acupuncture and compare the findings with traditional general linear model (GLM) methods. 30 healthy volunteers were recruited for this study. Block-designed manual acupuncture stimuli were delivered at SP6, and de qi sensations were measured after acupuncture stimulation. All subjects underwent functional MRI (fMRI) scanning during the acupuncture stimuli. The fMRI data were separately analysed by ISS and traditional GLM methods. All subjects experienced de qi sensations. ISS analysis showed that the regions activated during acupuncture stimulation at SP6 were mainly divided into five clusters based on the time courses. The time courses of clusters 1 and 2 were in line with the acupuncture stimulation pattern, and the active regions were mainly involved in the sensorimotor system and salience network. Clusters 3, 4 and 5 displayed an almost contrary time course relative to the stimulation pattern. The brain regions activated included the default mode network, descending pain modulation pathway and visual cortices. GLM analysis indicated that the brain responses associated with the instant effects of acupuncture were largely implicated in sensory and motor processing and sensory integration. The ISS analysis considered the sustained effect of acupuncture and uncovered additional information not shown by GLM analysis. We suggest that ISS may be a suitable approach to investigate the brain responses associated with the instant effects of acupuncture. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Brain response to visual sexual stimuli in homosexual pedophiles

PubMed Central

Schiffer, Boris; Krueger, Tillmann; Paul, Thomas; de Greiff, Armin; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Gizewski, Elke

2008-01-01

Objective The neurobiological mechanisms of deviant sexual preferences such as pedophilia are largely unknown. The objective of this study was to analyze whether brain activation patterns of homosexual pedophiles differed from those of a nonpedophile homosexual control group during visual sexual stimulation. Method A consecutive sample of 11 pedophile forensic inpatients exclusively attracted to boys and 12 age-matched homosexual control participants from a comparable socioeconomic stratum underwent functional magnetic resonance imaging during a visual sexual stimulation procedure that used sexually stimulating and emotionally neutral photographs. Sexual arousal was assessed according to a subjective rating scale. Results In contrast to sexually neutral pictures, in both groups sexually arousing pictures having both homosexual and pedophile content activated brain areas known to be involved in processing visual stimuli containing emotional content, including the occipitotemporal and prefrontal cortices. However, during presentation of the respective sexual stimuli, the thalamus, globus pallidus and striatum, which correspond to the key areas of the brain involved in sexual arousal and behaviour, showed significant activation in pedophiles, but not in control subjects. Conclusions Central processing of visual sexual stimuli in homosexual pedophiles seems to be comparable to that in nonpedophile control subjects. However, compared with homosexual control subjects, activation patterns in pedophiles refer more strongly to subcortical regions, which have previously been discussed in the context of processing reward signals and also play an important role in addictive and stimulus-controlled behaviour. Thus future studies should further elucidate the specificity of these brain regions for the processing of sexual stimuli in pedophilia and should address the generally weaker activation pattern in homosexual men. PMID:18197269

Brain response to visual sexual stimuli in homosexual pedophiles.

PubMed

Schiffer, Boris; Krueger, Tillmann; Paul, Thomas; de Greiff, Armin; Forsting, Michael; Leygraf, Norbert; Schedlowski, Manfred; Gizewski, Elke

2008-01-01

The neurobiological mechanisms of deviant sexual preferences such as pedophilia are largely unknown. The objective of this study was to analyze whether brain activation patterns of homosexual pedophiles differed from those of a nonpedophile homosexual control group during visual sexual stimulation. A consecutive sample of 11 pedophile forensic inpatients exclusively attracted to boys and 12 age-matched homosexual control participants from a comparable socioeconomic stratum underwent functional magnetic resonance imaging during a visual sexual stimulation procedure that used sexually stimulating and emotionally neutral photographs. Sexual arousal was assessed according to a subjective rating scale. In contrast to sexually neutral pictures, in both groups sexually arousing pictures having both homosexual and pedophile content activated brain areas known to be involved in processing visual stimuli containing emotional content, including the occipitotemporal and prefrontal cortices. However, during presentation of the respective sexual stimuli, the thalamus, globus pallidus and striatum, which correspond to the key areas of the brain involved in sexual arousal and behaviour, showed significant activation in pedophiles, but not in control subjects. Central processing of visual sexual stimuli in homosexual pedophiles seems to be comparable to that in nonpedophile control subjects. However, compared with homosexual control subjects, activation patterns in pedophiles refer more strongly to subcortical regions, which have previously been discussed in the context of processing reward signals and also play an important role in addictive and stimulus-controlled behaviour. Thus future studies should further elucidate the specificity of these brain regions for the processing of sexual stimuli in pedophilia and should address the generally weaker activation pattern in homosexual men.

Explicit and Implicit Second Language Training Differentially Affect the Achievement of Native-like Brain Activation Patterns

PubMed Central

Morgan-Short, Kara; Steinhauer, Karsten; Sanz, Cristina; Ullman, Michael T.

2013-01-01

It is widely believed that adults cannot learn a foreign language in the same way that children learn a first language. However, recent evidence suggests that adult learners of a foreign language can come to rely on native-like language brain mechanisms. Here, we show that the type of language training crucially impacts this outcome. We used an artificial language paradigm to examine longitudinally whether explicit training (that approximates traditional grammar-focused classroom settings) and implicit training (that approximates immersion settings) differentially affect neural (electrophysiological) and behavioral (performance) measures of syntactic processing. Results showed that performance of explicitly and implicitly trained groups did not differ at either low or high proficiency. In contrast, electrophysiological (ERP) measures revealed striking differences between the groups’ neural activity at both proficiency levels in response to syntactic violations. Implicit training yielded an N400 at low proficiency, whereas at high proficiency, it elicited a pattern typical of native speakers: an anterior negativity followed by a P600 accompanied by a late anterior negativity. Explicit training, by contrast, yielded no significant effects at low proficiency and only an anterior positivity followed by a P600 at high proficiency. Although the P600 is reminiscent of native-like processing, this response pattern as a whole is not. Thus, only implicit training led to an electrophysiological signature typical of native speakers. Overall, the results suggest that adult foreign language learners can come to rely on native-like language brain mechanisms, but that the conditions under which the language is learned may be crucial in attaining this goal. PMID:21861686

A tool for classifying individuals with chronic back pain: using multivariate pattern analysis with functional magnetic resonance imaging data.

PubMed

Callan, Daniel; Mills, Lloyd; Nott, Connie; England, Robert; England, Shaun

2014-01-01

Chronic pain is one of the most prevalent health problems in the world today, yet neurological markers, critical to diagnosis of chronic pain, are still largely unknown. The ability to objectively identify individuals with chronic pain using functional magnetic resonance imaging (fMRI) data is important for the advancement of diagnosis, treatment, and theoretical knowledge of brain processes associated with chronic pain. The purpose of our research is to investigate specific neurological markers that could be used to diagnose individuals experiencing chronic pain by using multivariate pattern analysis with fMRI data. We hypothesize that individuals with chronic pain have different patterns of brain activity in response to induced pain. This pattern can be used to classify the presence or absence of chronic pain. The fMRI experiment consisted of alternating 14 seconds of painful electric stimulation (applied to the lower back) with 14 seconds of rest. We analyzed contrast fMRI images in stimulation versus rest in pain-related brain regions to distinguish between the groups of participants: 1) chronic pain and 2) normal controls. We employed supervised machine learning techniques, specifically sparse logistic regression, to train a classifier based on these contrast images using a leave-one-out cross-validation procedure. We correctly classified 92.3% of the chronic pain group (N = 13) and 92.3% of the normal control group (N = 13) by recognizing multivariate patterns of activity in the somatosensory and inferior parietal cortex. This technique demonstrates that differences in the pattern of brain activity to induced pain can be used as a neurological marker to distinguish between individuals with and without chronic pain. Medical, legal and business professionals have recognized the importance of this research topic and of developing objective measures of chronic pain. This method of data analysis was very successful in correctly classifying each of the two groups.

A Tool for Classifying Individuals with Chronic Back Pain: Using Multivariate Pattern Analysis with Functional Magnetic Resonance Imaging Data

PubMed Central

Callan, Daniel; Mills, Lloyd; Nott, Connie; England, Robert; England, Shaun

2014-01-01

Chronic pain is one of the most prevalent health problems in the world today, yet neurological markers, critical to diagnosis of chronic pain, are still largely unknown. The ability to objectively identify individuals with chronic pain using functional magnetic resonance imaging (fMRI) data is important for the advancement of diagnosis, treatment, and theoretical knowledge of brain processes associated with chronic pain. The purpose of our research is to investigate specific neurological markers that could be used to diagnose individuals experiencing chronic pain by using multivariate pattern analysis with fMRI data. We hypothesize that individuals with chronic pain have different patterns of brain activity in response to induced pain. This pattern can be used to classify the presence or absence of chronic pain. The fMRI experiment consisted of alternating 14 seconds of painful electric stimulation (applied to the lower back) with 14 seconds of rest. We analyzed contrast fMRI images in stimulation versus rest in pain-related brain regions to distinguish between the groups of participants: 1) chronic pain and 2) normal controls. We employed supervised machine learning techniques, specifically sparse logistic regression, to train a classifier based on these contrast images using a leave-one-out cross-validation procedure. We correctly classified 92.3% of the chronic pain group (N = 13) and 92.3% of the normal control group (N = 13) by recognizing multivariate patterns of activity in the somatosensory and inferior parietal cortex. This technique demonstrates that differences in the pattern of brain activity to induced pain can be used as a neurological marker to distinguish between individuals with and without chronic pain. Medical, legal and business professionals have recognized the importance of this research topic and of developing objective measures of chronic pain. This method of data analysis was very successful in correctly classifying each of the two groups. PMID:24905072

Whole Brain Functional Connectivity Pattern Homogeneity Mapping.

PubMed

Wang, Lijie; Xu, Jinping; Wang, Chao; Wang, Jiaojian

2018-01-01

Mounting studies have demonstrated that brain functions are determined by its external functional connectivity patterns. However, how to characterize the voxel-wise similarity of whole brain functional connectivity pattern is still largely unknown. In this study, we introduced a new method called functional connectivity homogeneity (FcHo) to delineate the voxel-wise similarity of whole brain functional connectivity patterns. FcHo was defined by measuring the whole brain functional connectivity patterns similarity of a given voxel with its nearest 26 neighbors using Kendall's coefficient concordance (KCC). The robustness of this method was tested in four independent datasets selected from a large repository of MRI. Furthermore, FcHo mapping results were further validated using the nearest 18 and six neighbors and intra-subject reproducibility with each subject scanned two times. We also compared FcHo distribution patterns with local regional homogeneity (ReHo) to identify the similarity and differences of the two methods. Finally, FcHo method was used to identify the differences of whole brain functional connectivity patterns between professional Chinese chess players and novices to test its application. FcHo mapping consistently revealed that the high FcHo was mainly distributed in association cortex including parietal lobe, frontal lobe, occipital lobe and default mode network (DMN) related areas, whereas the low FcHo was mainly found in unimodal cortex including primary visual cortex, sensorimotor cortex, paracentral lobule and supplementary motor area. These results were further supported by analyses of the nearest 18 and six neighbors and intra-subject similarity. Moreover, FcHo showed both similar and different whole brain distribution patterns compared to ReHo. Finally, we demonstrated that FcHo can effectively identify the whole brain functional connectivity pattern differences between professional Chinese chess players and novices. Our findings indicated that FcHo is a reliable method to delineate the whole brain functional connectivity pattern similarity and may provide a new way to study the functional organization and to reveal neuropathological basis for brain disorders.

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.

Altered metabolic activity in the developing brain of rats predisposed to high versus low depression-like behavior

PubMed Central

Melendez-Ferro, Miguel; Perez-Costas, Emma; Glover, Matthew E.; Jackson, Nateka L.; Stringfellow, Sara A.; Pugh, Phyllis C.; Fant, Andrew D.; Clinton, Sarah M.

2016-01-01

Individual differences in human temperament can increase risk for psychiatric disorders like depression and anxiety. Our laboratory utilized a rat model of temperamental differences to assess neurodevelopmental factors underlying emotional behavior differences. Rats selectively bred for low novelty exploration (Low Responders, LR) display high levels of anxiety- and depression-like behavior compared to High Novelty Responder (HR) rats. Using transcriptome profiling, the present study uncovered vast gene expression differences in the early postnatal HR versus LR limbic brain, including changes in genes involved in cellular metabolism. These data led us to hypothesize that rats prone to high (versus low) anxiety/depression-like behavior exhibit distinct patterns of brain metabolism during the first weeks of life, which may reflect disparate patterns of synaptogenesis and brain circuit development. Thus, in a second experiment we examined activity of Cytochrome C Oxidase (COX), an enzyme responsible for ATP production and a correlate of metabolic activity, to explore functional energetic differences in HR/LR early postnatal brain. We found that HR rats display higher COX activity in the amygdala and specific hippocampal subregions compared to LRs during the first 2 weeks of life. Correlational analysis examining COX levels across several brain regions and multiple early postnatal time points suggested desynchronization in the developmental timeline of the limbic HR versus LR brain during the first two postnatal weeks. These early divergent COX activity levels may reflect altered circuitry or synaptic activity in the early postnatal HR/LR brain, which could contribute to the emergence of their distinct behavioral phenotypes. PMID:26979051

Central neural coding of sky polarization in insects.

PubMed

Homberg, Uwe; Heinze, Stanley; Pfeiffer, Keram; Kinoshita, Michiyo; el Jundi, Basil

2011-03-12

Many animals rely on a sun compass for spatial orientation and long-range navigation. In addition to the Sun, insects also exploit the polarization pattern and chromatic gradient of the sky for estimating navigational directions. Analysis of polarization-vision pathways in locusts and crickets has shed first light on brain areas involved in sky compass orientation. Detection of sky polarization relies on specialized photoreceptor cells in a small dorsal rim area of the compound eye. Brain areas involved in polarization processing include parts of the lamina, medulla and lobula of the optic lobe and, in the central brain, the anterior optic tubercle, the lateral accessory lobe and the central complex. In the optic lobe, polarization sensitivity and contrast are enhanced through convergence and opponency. In the anterior optic tubercle, polarized-light signals are integrated with information on the chromatic contrast of the sky. Tubercle neurons combine responses to the UV/green contrast and e-vector orientation of the sky and compensate for diurnal changes of the celestial polarization pattern associated with changes in solar elevation. In the central complex, a topographic representation of e-vector tunings underlies the columnar organization and suggests that this brain area serves as an internal compass coding for spatial directions.

Central neural coding of sky polarization in insects

PubMed Central

Homberg, Uwe; Heinze, Stanley; Pfeiffer, Keram; Kinoshita, Michiyo; el Jundi, Basil

2011-01-01

Many animals rely on a sun compass for spatial orientation and long-range navigation. In addition to the Sun, insects also exploit the polarization pattern and chromatic gradient of the sky for estimating navigational directions. Analysis of polarization–vision pathways in locusts and crickets has shed first light on brain areas involved in sky compass orientation. Detection of sky polarization relies on specialized photoreceptor cells in a small dorsal rim area of the compound eye. Brain areas involved in polarization processing include parts of the lamina, medulla and lobula of the optic lobe and, in the central brain, the anterior optic tubercle, the lateral accessory lobe and the central complex. In the optic lobe, polarization sensitivity and contrast are enhanced through convergence and opponency. In the anterior optic tubercle, polarized-light signals are integrated with information on the chromatic contrast of the sky. Tubercle neurons combine responses to the UV/green contrast and e-vector orientation of the sky and compensate for diurnal changes of the celestial polarization pattern associated with changes in solar elevation. In the central complex, a topographic representation of e-vector tunings underlies the columnar organization and suggests that this brain area serves as an internal compass coding for spatial directions. PMID:21282171

From phase transitions to the topological renaissance. Comment on "Topodynamics of metastable brains" by Arturo Tozzi et al.

NASA Astrophysics Data System (ADS)

Somogyvári, Zoltán; Érdi, Péter

2017-07-01

The neural topodynamics theory of Tozzi et al. [13] has two main foci: metastable brain dynamics and the topological approach based on the Borsuk-Ulam theorem (BUT). Briefly, metastable brain dynamics theory hypothesizes that temporary stable synchronization and desynchronization of large number of individual dynamical systems, formed by local neural circuits, are responsible for coding of complex concepts in the brain and sudden changes of these synchronization patterns correspond to operational steps. But what dynamical network could form the substrate for this metastable dynamics, capable of entering into a combinatorially high number of metastable synchronization patterns and exhibit rapid transient changes between them? The general problem is related to the discrimination between ;Black Swans; and ;Dragon Kings;. While BSs are related to the theory of self-organized criticality, and suggests that high-impact extreme events are unpredictable, Dragon-kings are associated with the occurrence of a phase transition, whose emergent organization is based on intermittent criticality [9]. Widening the limits of predictability is one of the big open problems in the theory and practice of complex systems (Sect. 9.3 of Érdi [2]).

Neural representation of emotion regulation goals.

PubMed

Morawetz, Carmen; Bode, Stefan; Baudewig, Juergen; Jacobs, Arthur M; Heekeren, Hauke R

2016-02-01

The use of top-down cognitive control mechanisms to regulate emotional responses as circumstances change is critical for mental and physical health. Several theoretical models of emotion regulation have been postulated; it remains unclear, however, in which brain regions emotion regulation goals (e.g., the downregulation of fear) are represented. Here, we examined the neural mechanisms of regulating emotion using fMRI and identified brain regions representing reappraisal goals. Using a multimethodological analysis approach, combining standard activation-based and pattern-information analyses, we identified a distributed network of lateral frontal, temporal, and parietal regions implicated in reappraisal and within it, a core system that represents reappraisal goals in an abstract, stimulus-independent fashion. Within this core system, the neural pattern-separability in a subset of regions including the left inferior frontal gyrus, middle temporal gyrus, and inferior parietal lobe was related to the success in emotion regulation. Those brain regions might link the prefrontal control regions with the subcortical affective regions. Given the strong association of this subsystem with inner speech functions and semantic memory, we conclude that those cognitive mechanisms may be used for orchestrating emotion regulation. Hum Brain Mapp 37:600-620, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

An fMRI study of theory of mind in schizophrenic patients with "passivity" symptoms.

PubMed

Brüne, Martin; Lissek, Silke; Fuchs, Nina; Witthaus, Henning; Peters, Sören; Nicolas, Volkmar; Juckel, Georg; Tegenthoff, Martin

2008-01-01

Several studies have shown that patients with schizophrenia underactivate brain regions involved in theory of mind relative to controls during functional brain imaging. However, in most studies the samples were fairly heterogeneous in terms of clinical symptomatology. We examined a group of nine patients with first episode or recurrent episodes, who clinically presented with predominant "passivity" symptoms such as third-person auditory hallucinations or delusion of control, using a cartoon-based theory of mind task and compared activation patterns with a group of 13 healthy controls. All patients responded well to antipsychotic treatment and were only mildly symptomatic at the time of testing. The patient group showed significantly less activation of the right anterior cingulate cortex (ACC) and right insula compared with controls, but greater activation in dorsal areas of the medial prefrontal cortex, right temporal areas and left temporo-parietal junction. Patients with schizophrenia with predominant "passivity" symptoms and good response to antipsychotic treatment show a markedly diverging pattern of brain activation during theory of mind task performance compared with healthy controls. These findings suggest abnormal activation of those brain areas involved in the evaluation of self-reference during mental state attribution.

Combining self-organizing mapping and supervised affinity propagation clustering approach to investigate functional brain networks involved in motor imagery and execution with fMRI measurements.

PubMed

Zhang, Jiang; Liu, Qi; Chen, Huafu; Yuan, Zhen; Huang, Jin; Deng, Lihua; Lu, Fengmei; Zhang, Junpeng; Wang, Yuqing; Wang, Mingwen; Chen, Liangyin

2015-01-01

Clustering analysis methods have been widely applied to identifying the functional brain networks of a multitask paradigm. However, the previously used clustering analysis techniques are computationally expensive and thus impractical for clinical applications. In this study a novel method, called SOM-SAPC that combines self-organizing mapping (SOM) and supervised affinity propagation clustering (SAPC), is proposed and implemented to identify the motor execution (ME) and motor imagery (MI) networks. In SOM-SAPC, SOM was first performed to process fMRI data and SAPC is further utilized for clustering the patterns of functional networks. As a result, SOM-SAPC is able to significantly reduce the computational cost for brain network analysis. Simulation and clinical tests involving ME and MI were conducted based on SOM-SAPC, and the analysis results indicated that functional brain networks were clearly identified with different response patterns and reduced computational cost. In particular, three activation clusters were clearly revealed, which include parts of the visual, ME and MI functional networks. These findings validated that SOM-SAPC is an effective and robust method to analyze the fMRI data with multitasks.

Association Between Brain Activation and Functional Connectivity.

PubMed

Tomasi, Dardo; Volkow, Nora D

2018-04-13

The origin of the "resting-state" brain activity recorded with functional magnetic resonance imaging (fMRI) is still uncertain. Here we provide evidence for the neurovascular origins of the amplitude of the low-frequency fluctuations (ALFF) and the local functional connectivity density (lFCD) by comparing them with task-induced blood-oxygen level dependent (BOLD) responses, which are considered a proxy for neuronal activation. Using fMRI data for 2 different tasks (Relational and Social) collected by the Human Connectome Project in 426 healthy adults, we show that ALFF and lFCD have linear associations with the BOLD response. This association was significantly attenuated by a novel task signal regression (TSR) procedure, indicating that task performance enhances lFCD and ALFF in activated regions. We also show that lFCD predicts BOLD activation patterns, as was recently shown for other functional connectivity metrics, which corroborates that resting functional connectivity architecture impacts brain activation responses. Thus, our findings indicate a common source for BOLD responses, ALFF and lFCD, which is consistent with the neurovascular origin of local hemodynamic synchrony presumably reflecting coordinated fluctuations in neuronal activity. This study also supports the development of task-evoked functional connectivity density mapping.

Reference frames for spatial frequency in face representation differ in the temporal visual cortex and amygdala.

PubMed

Inagaki, Mikio; Fujita, Ichiro

2011-07-13

Social communication in nonhuman primates and humans is strongly affected by facial information from other individuals. Many cortical and subcortical brain areas are known to be involved in processing facial information. However, how the neural representation of faces differs across different brain areas remains unclear. Here, we demonstrate that the reference frame for spatial frequency (SF) tuning of face-responsive neurons differs in the temporal visual cortex and amygdala in monkeys. Consistent with psychophysical properties for face recognition, temporal cortex neurons were tuned to image-based SFs (cycles/image) and showed viewing distance-invariant representation of face patterns. On the other hand, many amygdala neurons were influenced by retina-based SFs (cycles/degree), a characteristic that is useful for social distance computation. The two brain areas also differed in the luminance contrast sensitivity of face-responsive neurons; amygdala neurons sharply reduced their responses to low luminance contrast images, while temporal cortex neurons maintained the level of their responses. From these results, we conclude that different types of visual processing in the temporal visual cortex and the amygdala contribute to the construction of the neural representations of faces.

Temporal profile of brain response to alprazolam in patients with generalized anxiety disorder.

PubMed

Brown, Gregory G; Ostrowitzki, Susanne; Stein, Murray B; von Kienlin, Markus; Liu, Thomas T; Simmons, Alan; Wierenga, Christina; Stein, Orah Y; Bruns, Andreas; Bischoff-Grethe, Amanda; Paulus, Martin

2015-09-30

This study investigated the temporal pattern of brain response to emotional stimuli during 28 days of alprazolam treatment among patients with generalized anxiety disorder (GAD) randomized 2:1 to drug or placebo in a double-blind design. Functional magnetic resonance imaging scans obtained during an emotion face matching task (EFMT) and an affective stimulus expectancy task (STIMEX) were performed at baseline, one hour after initial drug administration and 28 days later. Alprazolam significantly reduced scores on the Hamilton Anxiety Scale and the Penn State Worry Questionnaire after one week and 28 days of treatment. Brain activation in the amygdala during the EFMT and in the insula during the STIMEX was reduced one hour after alprazolam administration but returned to baseline levels at Day 28. Exploratory analyses revealed significant treatment differences in brain activity during the STIMEX on Day 28 in frontal lobe, caudate nucleus, middle temporal gyrus, secondary visual cortex, and supramarginal gyrus. These results are consistent with the notion that the neural mechanisms supporting sustained treatment effects of benzodiazepines in GAD differ from those underlying their acute effects. Published by Elsevier Ireland Ltd.

Common resting brain dynamics indicate a possible mechanism underlying zolpidem response in severe brain injury

PubMed Central

Williams, Shawniqua T; Conte, Mary M; Goldfine, Andrew M; Noirhomme, Quentin; Gosseries, Olivia; Thonnard, Marie; Beattie, Bradley; Hersh, Jennifer; Katz, Douglas I; Victor, Jonathan D; Laureys, Steven; Schiff, Nicholas D

2013-01-01

Zolpidem produces paradoxical recovery of speech, cognitive and motor functions in select subjects with severe brain injury but underlying mechanisms remain unknown. In three diverse patients with known zolpidem responses we identify a distinctive pattern of EEG dynamics that suggests a mechanistic model. In the absence of zolpidem, all subjects show a strong low frequency oscillatory peak ∼6–10 Hz in the EEG power spectrum most prominent over frontocentral regions and with high coherence (∼0.7–0.8) within and between hemispheres. Zolpidem administration sharply reduces EEG power and coherence at these low frequencies. The ∼6–10 Hz activity is proposed to arise from intrinsic membrane properties of pyramidal neurons that are passively entrained across the cortex by locally-generated spontaneous activity. Activation by zolpidem is proposed to arise from a combination of initial direct drug effects on cortical, striatal, and thalamic populations and further activation of underactive brain regions induced by restoration of cognitively-mediated behaviors. DOI: http://dx.doi.org/10.7554/eLife.01157.001 PMID:24252875

Decreased functional brain activation in Friedreich ataxia using the Simon effect task.

PubMed

Georgiou-Karistianis, N; Akhlaghi, H; Corben, L A; Delatycki, M B; Storey, E; Bradshaw, J L; Egan, G F

2012-08-01

The present study applied the Simon effect task to examine the pattern of functional brain reorganization in individuals with Friedreich ataxia (FRDA), using functional magnetic resonance imaging (fMRI). Thirteen individuals with FRDA and 14 age and sex matched controls participated, and were required to respond to either congruent or incongruent arrow stimuli, presented either to the left or right of a screen, via laterally-located button press responses. Although the Simon effect (incongruent minus congruent stimuli) showed common regions of activation in both groups, including the superior and middle prefrontal cortices, insulae, superior and inferior parietal lobules (LPs, LPi), occipital cortex and cerebellum, there was reduced functional activation across a range of brain regions (cortical, subcortical and cerebellar) in individuals with FRDA. The greater Simon effect behaviourally in individuals with FRDA, compared with controls, together with concomitant reductions in functional brain activation and reduced functional connectivity between cortical and sub-cortical regions, implies a likely disruption of cortico-cerebellar loops and ineffective engagement of cognitive/attention regions required for response suppression. Copyright © 2012 Elsevier Inc. All rights reserved.

Single Trial Brain Electrical Patterns of an Auditory and Visual Perceptuomotor Task.

DTIC Science & Technology

1983-06-01

perceptual and cognitive processing was completed, a motor program common to both tasks was executed, regardless of differences in the stimuli or type...investigation and conclusions concerning these issues during the developmental program of 12 pilot recordings is reported in the following section. B. Task...number on the CRT screen (duration 375 msec) I second after completion of response as determined by the program . If the response was sufficiently accurate

Infants’ brain responses to speech suggest Analysis by Synthesis

PubMed Central

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

2014-01-01

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

Infants' brain responses to speech suggest analysis by synthesis.

PubMed

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

2014-08-05

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

Neural evidence of motivational conflict between social values.

PubMed

Leszkowicz, Emilia; Linden, David E J; Maio, Gregory R; Ihssen, Niklas

2017-10-01

Motivational interdependence is an organizing principle in Schwartz's circumplex model of social values, which has received abundant cross-cultural support. We used fMRI to test whether motivational relations between social values predict different brain responses in a situation of choice between values. We hypothesized that differences in brain responses would become evident when the more important value had to be selected in pairs of congruent (e.g., wealth and success) as opposed to incongruent (e.g., curiosity and stability) values as they are described in Schwartz's model, because the former serve mutually facilitating motives, whereas the latter serve mutually inhibiting motives. Consistent with the model, choosing between congruent values led to longer response times and more activation in conflict-related brain regions (e.g., the supplementary motor area, dorsolateral prefrontal cortex) than selecting between incongruent values. These results provide novel neural evidence supporting the circumplex model's predictions about motivational interdependence between social values. In particular, our results show that the neural networks underlying social values are organized in a way that allows activation patterns related to motivational similarity between congruent values to be dissociated from those related to incongruent values.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-01-01

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

Within-Subject Correlation Analysis to Detect Functional Areas Associated With Response Inhibition.

PubMed

Yamasaki, Tomoko; Ogawa, Akitoshi; Osada, Takahiro; Jimura, Koji; Konishi, Seiki

2018-01-01

Functional areas in fMRI studies are often detected by brain-behavior correlation, calculating across-subject correlation between the behavioral index and the brain activity related to a function of interest. Within-subject correlation analysis is also employed in a single subject level, which utilizes cognitive fluctuations in a shorter time period by correlating the behavioral index with the brain activity across trials. In the present study, the within-subject analysis was applied to the stop-signal task, a standard task to probe response inhibition, where efficiency of response inhibition can be evaluated by the stop-signal reaction time (SSRT). Since the SSRT is estimated, by definition, not in a trial basis but from pooled trials, the correlation across runs was calculated between the SSRT and the brain activity related to response inhibition. The within-subject correlation revealed negative correlations in the anterior cingulate cortex and the cerebellum. Moreover, the dissociation pattern was observed in the within-subject analysis when earlier vs. later parts of the runs were analyzed: negative correlation was dominant in earlier runs, whereas positive correlation was dominant in later runs. Regions of interest analyses revealed that the negative correlation in the anterior cingulate cortex, but not in the cerebellum, was dominant in earlier runs, suggesting multiple mechanisms associated with inhibitory processes that fluctuate on a run-by-run basis. These results indicate that the within-subject analysis compliments the across-subject analysis by highlighting different aspects of cognitive/affective processes related to response inhibition.

Assessment of sexual orientation using the hemodynamic brain response to visual sexual stimuli.

PubMed

Ponseti, Jorge; Granert, Oliver; Jansen, Olav; Wolff, Stephan; Mehdorn, Hubertus; Bosinski, Hartmut; Siebner, Hartwig

2009-06-01

The assessment of sexual orientation is of importance to the diagnosis and treatment of sex offenders and paraphilic disorders. Phallometry is considered gold standard in objectifying sexual orientation, yet this measurement has been criticized because of its intrusiveness and limited reliability. To evaluate whether the spatial response pattern to sexual stimuli as revealed by a change in blood oxygen level-dependent (BOLD) signal can be used for individual classification of sexual orientation. We used a preexisting functional MRI (fMRI) data set that had been acquired in a nonclinical sample of 12 heterosexual men and 14 homosexual men. During fMRI, participants were briefly exposed to pictures of same-sex and opposite-sex genitals. Data analysis involved four steps: (i) differences in the BOLD response to female and male sexual stimuli were calculated for each subject; (ii) these contrast images were entered into a group analysis to calculate whole-brain difference maps between homosexual and heterosexual participants; (iii) a single expression value was computed for each subject expressing its correspondence to the group result; and (iv) based on these expression values, Fisher's linear discriminant analysis and the kappa-nearest neighbor classification method were used to predict the sexual orientation of each subject. Sensitivity and specificity of the two classification methods in predicting individual sexual orientation. Both classification methods performed well in predicting individual sexual orientation with a mean accuracy of >85% (Fisher's linear discriminant analysis: 92% sensitivity, 85% specificity; kappa-nearest neighbor classification: 88% sensitivity, 92% specificity). Despite the small sample size, the functional response patterns of the brain to sexual stimuli contained sufficient information to predict individual sexual orientation with high accuracy. These results suggest that fMRI-based classification methods hold promise for the diagnosis of paraphilic disorders (e.g., pedophilia).

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.

Epigenetic and gene expression changes in the adolescent brain: What have we learned from animal models?

PubMed

Mychasiuk, Richelle; Metz, Gerlinde A S

2016-11-01

Adolescence is defined as the gradual period of transition between childhood and adulthood that is characterized by significant brain maturation, growth spurts, sexual maturation, and heightened social interaction. Although originally believed to be a uniquely human aspect of development, rodent and non-human primates demonstrate maturational patterns that distinctly support an adolescent stage. As epigenetic processes are essential for development and differentiation, but also transpire in mature cells in response to environmental influences, they are an important aspect of adolescent brain maturation. The purpose of this review article was to examine epigenetic programming in animal models of brain maturation during adolescence. The discussion focuses on animal models to examine three main concepts; epigenetic processes involved in normal adolescent brain maturation, the influence of fetal programming on adolescent brain development and the epigenome, and finally, postnatal experiences such as exercise and drugs that modify epigenetic processes important for adolescent brain maturation. This corollary emphasizes the utility of animal models to further our understanding of complex processes such as epigenetic regulation and brain development. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2008-01-01

Visuo-attentional deficits occur early in Alzheimer's disease (AD) and are considered more responsive to pro-cholinergic therapy than characteristic memory disturbances. We hypothesised that neural responses in AD during visual attentional processing would be impaired relative to controls, yet partially susceptible to improvement with cholinesterase inhibition. We studied 16 mild AD patients and 17 age-matched healthy controls, using fMRI-scanning to enable within-subject placebo-controlled comparisons of the effects of physostigmine on stimulus- and attention-related brain activations, and to allow between-group comparisons for these. Subjects viewed stimuli comprising faces or buildings while performing a shallow judgement (colour of image) or a deep judgement (young/old age of depicted face or building). Behaviourally, AD subjects performed poorer than controls in both tasks, while physostigmine benefited AD patients for the more demanding age-judgement task. Stimulus-selective (face minus building, and vice versa) BOLD signals in precuneus and posterior parahippocampal cortex were attenuated in AD relative to controls but increased following physostigmine. By contrast, face-selective responses in fusiform cortex were not impaired in AD and showed decreases following physostigmine for both groups. Task-dependent responses in right parietal and prefrontal cortices were diminished in AD but improved following physostigmine. A similar pattern of group and treatment effects was observed in two extrastriate cortical regions that showed enhanced stimulus-selectivity for the deep versus shallow task. Finally, for the healthy group, physostigmine decreased task-dependent effects, partly due to an exaggeration of selectivity during the shallow relative to deep task. Our results demonstrate cholinergic-mediated improvements for both stimulus- and attention-dependent responses in functionally affected extrastriate and frontoparietal regions for AD. We also show that normal stimulus- and task-dependent activity patterns can be perturbed in the healthy brain by cholinergic stimulation. PMID:18077465

The Cluster Variation Method: A Primer for Neuroscientists.

PubMed

Maren, Alianna J

2016-09-30

Effective Brain-Computer Interfaces (BCIs) require that the time-varying activation patterns of 2-D neural ensembles be modelled. The cluster variation method (CVM) offers a means for the characterization of 2-D local pattern distributions. This paper provides neuroscientists and BCI researchers with a CVM tutorial that will help them to understand how the CVM statistical thermodynamics formulation can model 2-D pattern distributions expressing structural and functional dynamics in the brain. The premise is that local-in-time free energy minimization works alongside neural connectivity adaptation, supporting the development and stabilization of consistent stimulus-specific responsive activation patterns. The equilibrium distribution of local patterns, or configuration variables , is defined in terms of a single interaction enthalpy parameter ( h ) for the case of an equiprobable distribution of bistate (neural/neural ensemble) units. Thus, either one enthalpy parameter (or two, for the case of non-equiprobable distribution) yields equilibrium configuration variable values. Modeling 2-D neural activation distribution patterns with the representational layer of a computational engine, we can thus correlate variational free energy minimization with specific configuration variable distributions. The CVM triplet configuration variables also map well to the notion of a M = 3 functional motif. This paper addresses the special case of an equiprobable unit distribution, for which an analytic solution can be found.

Receptive fields of locust brain neurons are matched to polarization patterns of the sky.

PubMed

Bech, Miklós; Homberg, Uwe; Pfeiffer, Keram

2014-09-22

Many animals, including insects, are able to use celestial cues as a reference for spatial orientation and long-distance navigation [1]. In addition to direct sunlight, the chromatic gradient of the sky and its polarization pattern are suited to serve as orientation cues [2-5]. Atmospheric scattering of sunlight causes a regular pattern of E vectors in the sky, which are arranged along concentric circles around the sun [5, 6]. Although certain insects rely predominantly on sky polarization for spatial orientation [7], it has been argued that detection of celestial E vector orientation may not suffice to differentiate between solar and antisolar directions [8, 9]. We show here that polarization-sensitive (POL) neurons in the brain of the desert locust Schistocerca gregaria can overcome this ambiguity. Extracellular recordings from POL units in the central complex and lateral accessory lobes revealed E vector tunings arranged in concentric circles within large receptive fields, matching the sky polarization pattern at certain solar positions. Modeling of neuronal responses under an idealized sky polarization pattern (Rayleigh sky) suggests that these "matched filter" properties allow locusts to unambiguously determine the solar azimuth by relying solely on the sky polarization pattern for compass navigation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Influence of Alcohol Use on Neural Response to Go/No-Go Task in College Drinkers

PubMed Central

Ahmadi, Aral; Pearlson, Godfrey D; Meda, Shashwath A; Dager, Alecia; Potenza, Marc N; Rosen, Rivkah; Austad, Carol S; Raskin, Sarah A; Fallahi, Carolyn R; Tennen, Howard; Wood, Rebecca M; Stevens, Michael C

2013-01-01

Impaired inhibition of prepotent motor response may represent an important risk factor for alcoholism. Alcohol use may also increase impulsive behavior, including impaired response inhibition. Little is known about the brain function underlying response inhibition among college-age drinkers based on their drinking patterns, despite college-age drinkers demonstrating high rates of alcohol-use disorders. Our major objective was to compare behavior and associated brain activity measured with fMRI during a response-inhibition task in matched heavy- and light-alcohol-drinking college students. Participants were light (N=36) and heavy (N=56) drinkers, aged 18–20 years. We characterized blood oxygen level-dependent (BOLD) responses, while participants performed an fMRI Go/No-Go task to quantify inhibitory behavior and brain activity. Behaviorally, group performance differences were observed for Go correct-hit and No-Go false-alarm reaction times with increased reaction times in heavy compared with light drinkers. During fMRI No-Go correct rejections, light drinkers exhibited greater BOLD response than did heavy drinkers in left supplementary motor area (SMA), bilateral parietal lobule, right hippocampus, bilateral middle frontal gyrus, left superior temporal gyrus, and cingulate gyrus/anterior cingulate cortex (Brodmann area 24). Group differences in Go/No-Go-related regional activations correlated with alcohol- and impulsivity-related measures. These findings suggest that heavy alcohol drinkers may have dysfunction in brain regions underlying attention and response inhibition, leading to diminished abilities to suppress prepotent responding. The extent to which these tendencies relate to impulsive decision-making and behaviors in real-life settings and may guide intervention development warrants additional investigation. PMID:23670589

A high-resolution 7-Tesla fMRI dataset from complex natural stimulation with an audio movie

PubMed Central

Hanke, Michael; Baumgartner, Florian J.; Ibe, Pierre; Kaule, Falko R.; Pollmann, Stefan; Speck, Oliver; Zinke, Wolf; Stadler, Jörg

2014-01-01

Here we present a high-resolution functional magnetic resonance (fMRI) dataset – 20 participants recorded at high field strength (7 Tesla) during prolonged stimulation with an auditory feature film (“Forrest Gump”). In addition, a comprehensive set of auxiliary data (T1w, T2w, DTI, susceptibility-weighted image, angiography) as well as measurements to assess technical and physiological noise components have been acquired. An initial analysis confirms that these data can be used to study common and idiosyncratic brain response patterns to complex auditory stimulation. Among the potential uses of this dataset are the study of auditory attention and cognition, language and music perception, and social perception. The auxiliary measurements enable a large variety of additional analysis strategies that relate functional response patterns to structural properties of the brain. Alongside the acquired data, we provide source code and detailed information on all employed procedures – from stimulus creation to data analysis. In order to facilitate replicative and derived works, only free and open-source software was utilized. PMID:25977761

Cortical Representations of Symbols, Objects, and Faces Are Pruned Back during Early Childhood

PubMed Central

Pinel, Philippe; Dehaene, Stanislas; Pelphrey, Kevin A.

2011-01-01

Regions of human ventral extrastriate visual cortex develop specializations for natural categories (e.g., faces) and cultural artifacts (e.g., words). In adults, category-based specializations manifest as greater neural responses in visual regions of the brain (e.g., fusiform gyrus) to some categories over others. However, few studies have examined how these specializations originate in the brains of children. Moreover, it is as yet unknown whether the development of visual specializations hinges on “increases” in the response to the preferred categories, “decreases” in the responses to nonpreferred categories, or “both.” This question is relevant to a long-standing debate concerning whether neural development is driven by building up or pruning back representations. To explore these questions, we measured patterns of visual activity in 4-year-old children for 4 categories (faces, letters, numbers, and shoes) using functional magnetic resonance imaging. We report 2 key findings regarding the development of visual categories in the brain: 1) the categories “faces” and “symbols” doubly dissociate in the fusiform gyrus before children can read and 2) the development of category-specific responses in young children depends on cortical responses to nonpreferred categories that decrease as preferred category knowledge is acquired. PMID:20457691

Visceral Inflammation and Immune Activation Stress the Brain

PubMed Central

Holzer, Peter; Farzi, Aitak; Hassan, Ahmed M.; Zenz, Geraldine; Jačan, Angela; Reichmann, Florian

2017-01-01

Stress refers to a dynamic process in which the homeostasis of an organism is challenged, the outcome depending on the type, severity, and duration of stressors involved, the stress responses triggered, and the stress resilience of the organism. Importantly, the relationship between stress and the immune system is bidirectional, as not only stressors have an impact on immune function, but alterations in immune function themselves can elicit stress responses. Such bidirectional interactions have been prominently identified to occur in the gastrointestinal tract in which there is a close cross-talk between the gut microbiota and the local immune system, governed by the permeability of the intestinal mucosa. External stressors disturb the homeostasis between microbiota and gut, these disturbances being signaled to the brain via multiple communication pathways constituting the gut–brain axis, ultimately eliciting stress responses and perturbations of brain function. In view of these relationships, the present article sets out to highlight some of the interactions between peripheral immune activation, especially in the visceral system, and brain function, behavior, and stress coping. These issues are exemplified by the way through which the intestinal microbiota as well as microbe-associated molecular patterns including lipopolysaccharide communicate with the immune system and brain, and the mechanisms whereby overt inflammation in the GI tract impacts on emotional-affective behavior, pain sensitivity, and stress coping. The interactions between the peripheral immune system and the brain take place along the gut–brain axis, the major communication pathways of which comprise microbial metabolites, gut hormones, immune mediators, and sensory neurons. Through these signaling systems, several transmitter and neuropeptide systems within the brain are altered under conditions of peripheral immune stress, enabling adaptive processes related to stress coping and resilience to take place. These aspects of the impact of immune stress on molecular and behavioral processes in the brain have a bearing on several disturbances of mental health and highlight novel opportunities of therapeutic intervention. PMID:29213271

Auditory cortical activity after intracortical microstimulation and its role for sensory processing and learning.

PubMed

Deliano, Matthias; Scheich, Henning; Ohl, Frank W

2009-12-16

Several studies have shown that animals can learn to make specific use of intracortical microstimulation (ICMS) of sensory cortex within behavioral tasks. Here, we investigate how the focal, artificial activation by ICMS leads to a meaningful, behaviorally interpretable signal. In natural learning, this involves large-scale activity patterns in widespread brain-networks. We therefore trained gerbils to discriminate closely neighboring ICMS sites within primary auditory cortex producing evoked responses largely overlapping in space. In parallel, during training, we recorded electrocorticograms (ECoGs) at high spatial resolution. Applying a multivariate classification procedure, we identified late spatial patterns that emerged with discrimination learning from the ongoing poststimulus ECoG. These patterns contained information about the preceding conditioned stimulus, and were associated with a subsequent correct behavioral response by the animal. Thereby, relevant pattern information was mainly carried by neuron populations outside the range of the lateral spatial spread of ICMS-evoked cortical activation (approximately 1.2 mm). This demonstrates that the stimulated cortical area not only encoded information about the stimulation sites by its focal, stimulus-driven activation, but also provided meaningful signals in its ongoing activity related to the interpretation of ICMS learned by the animal. This involved the stimulated area as a whole, and apparently required large-scale integration in the brain. However, ICMS locally interfered with the ongoing cortical dynamics by suppressing pattern formation near the stimulation sites. The interaction between ICMS and ongoing cortical activity has several implications for the design of ICMS protocols and cortical neuroprostheses, since the meaningful interpretation of ICMS depends on this interaction.

Face processing in autism spectrum disorders: from brain regions to brain networks

PubMed Central

Nomi, Jason S.; Uddin, Lucina Q.

2015-01-01

Autism spectrum disorder (ASD) is characterized by reduced attention to social stimuli including the human face. This hypo-responsiveness to stimuli that are engaging to typically developing individuals may result from dysfunctioning motivation, reward, and attention systems in the brain. Here we review an emerging neuroimaging literature that emphasizes a shift from focusing on hypo-activation of isolated brain regions such as the fusiform gyrus, amygdala, and superior temporal sulcus in ASD to a more holistic approach to understanding face perception as a process supported by distributed cortical and subcortical brain networks. We summarize evidence for atypical activation patterns within brain networks that may contribute to social deficits characteristic of the disorder. We conclude by pointing to gaps in the literature and future directions that will continue to shed light on aspects of face processing in autism that are still under-examined. In particular, we highlight the need for more developmental studies and studies examining ecologically valid and naturalistic social stimuli. PMID:25829246

Preserved Haptic Shape Processing after Bilateral LOC Lesions.

PubMed

Snow, Jacqueline C; Goodale, Melvyn A; Culham, Jody C

2015-10-07

The visual and haptic perceptual systems are understood to share a common neural representation of object shape. A region thought to be critical for recognizing visual and haptic shape information is the lateral occipital complex (LOC). We investigated whether LOC is essential for haptic shape recognition in humans by studying behavioral responses and brain activation for haptically explored objects in a patient (M.C.) with bilateral lesions of the occipitotemporal cortex, including LOC. Despite severe deficits in recognizing objects using vision, M.C. was able to accurately recognize objects via touch. M.C.'s psychophysical response profile to haptically explored shapes was also indistinguishable from controls. Using fMRI, M.C. showed no object-selective visual or haptic responses in LOC, but her pattern of haptic activation in other brain regions was remarkably similar to healthy controls. Although LOC is routinely active during visual and haptic shape recognition tasks, it is not essential for haptic recognition of object shape. The lateral occipital complex (LOC) is a brain region regarded to be critical for recognizing object shape, both in vision and in touch. However, causal evidence linking LOC with haptic shape processing is lacking. We studied recognition performance, psychophysical sensitivity, and brain response to touched objects, in a patient (M.C.) with extensive lesions involving LOC bilaterally. Despite being severely impaired in visual shape recognition, M.C. was able to identify objects via touch and she showed normal sensitivity to a haptic shape illusion. M.C.'s brain response to touched objects in areas of undamaged cortex was also very similar to that observed in neurologically healthy controls. These results demonstrate that LOC is not necessary for recognizing objects via touch. Copyright © 2015 the authors 0270-6474/15/3513745-16$15.00/0.

Zinc or copper deficiency-induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes.

PubMed

Penkowa, M; Giralt, M; Thomsen, P S; Carrasco, J; Hidalgo, J

2001-04-01

The role of zinc- and copper-deficient diets on the inflammatory response to traumatic brain injury (TBI) has been evaluated in adult rats. As expected, zinc deficiency decreased food intake and body weight gain, and the latter effect was higher than that observed in pair-fed rats. In noninjured brains, zinc deficiency only affected significantly lectin (increasing) and glial fibrillary acidic protein (GFAP) and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) (decreasing) immunoreactivities (irs). In injured brains, a profound gliosis was observed in the area surrounding the lesion, along with severe damage to neurons as indicated by neuron specific enolase (NSE) ir, and the number of cells undergoing apoptosis (measured by TUNEL) was dramatically increased. Zinc deficiency significantly altered brain response to TBI, potentiating the microgliosis and reducing the astrogliosis, while increasing the number of apoptotic cells. Metallothioneins (MTs) are important zinc- and copper-binding proteins in the CNS, which could influence significantly the brain response to TBI because of their putative roles in metal homeostasis and antioxidant defenses. MT-I+II expression was dramatically increased by TBI, and this response was significantly blunted by zinc deficiency. The MT-III isoform was moderately increased by both TBI and zinc deficiency. TBI strongly increased oxidative stress levels, as demonstrated by malondialdehyde (MDA), protein tyrosine nitration (NITT), and nuclear factor kappaB (NF-kappaB) levels irs, all of which were potentiated by zinc deficiency. Further analysis revealed unbalanced expression of prooxidant and antioxidant proteins besides MT, since the levels of inducible nitric oxide synthase (iNOS) and Cu,Zn-SOD were increased and decreased, respectively, by zinc deficiency. All these effects were attributable to zinc deficiency, since pair-fed rats did not differ from normally fed rats. In general, copper deficiency caused a similar pattern of responses, albeit more moderate. Results obtained in mice with a null mutation for the MT-I+II isoforms strongly suggest that most of the effects observed in the rat brain after zinc and copper deficiencies are attributable to the concomitant changes in the MT expression.

Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man.

PubMed

Kalafatakis, K; Russell, G M; Harmer, C J; Munafo, M R; Marchant, N; Wilson, A; Brooks, J C; Durant, C; Thakrar, J; Murphy, P; Thai, N J; Lightman, S L

2018-04-24

Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy.

Electrical Brain Responses to an Auditory Illusion and the Impact of Musical Expertise

PubMed Central

Ioannou, Christos I.; Pereda, Ernesto; Lindsen, Job P.; Bhattacharya, Joydeep

2015-01-01

The presentation of two sinusoidal tones, one to each ear, with a slight frequency mismatch yields an auditory illusion of a beating frequency equal to the frequency difference between the two tones; this is known as binaural beat (BB). The effect of brief BB stimulation on scalp EEG is not conclusively demonstrated. Further, no studies have examined the impact of musical training associated with BB stimulation, yet musicians' brains are often associated with enhanced auditory processing. In this study, we analysed EEG brain responses from two groups, musicians and non-musicians, when stimulated by short presentation (1 min) of binaural beats with beat frequency varying from 1 Hz to 48 Hz. We focused our analysis on alpha and gamma band EEG signals, and they were analysed in terms of spectral power, and functional connectivity as measured by two phase synchrony based measures, phase locking value and phase lag index. Finally, these measures were used to characterize the degree of centrality, segregation and integration of the functional brain network. We found that beat frequencies belonging to alpha band produced the most significant steady-state responses across groups. Further, processing of low frequency (delta, theta, alpha) binaural beats had significant impact on cortical network patterns in the alpha band oscillations. Altogether these results provide a neurophysiological account of cortical responses to BB stimulation at varying frequencies, and demonstrate a modulation of cortico-cortical connectivity in musicians' brains, and further suggest a kind of neuronal entrainment of a linear and nonlinear relationship to the beating frequencies. PMID:26065708

Electrical Brain Responses to an Auditory Illusion and the Impact of Musical Expertise.

PubMed

Ioannou, Christos I; Pereda, Ernesto; Lindsen, Job P; Bhattacharya, Joydeep

2015-01-01

The presentation of two sinusoidal tones, one to each ear, with a slight frequency mismatch yields an auditory illusion of a beating frequency equal to the frequency difference between the two tones; this is known as binaural beat (BB). The effect of brief BB stimulation on scalp EEG is not conclusively demonstrated. Further, no studies have examined the impact of musical training associated with BB stimulation, yet musicians' brains are often associated with enhanced auditory processing. In this study, we analysed EEG brain responses from two groups, musicians and non-musicians, when stimulated by short presentation (1 min) of binaural beats with beat frequency varying from 1 Hz to 48 Hz. We focused our analysis on alpha and gamma band EEG signals, and they were analysed in terms of spectral power, and functional connectivity as measured by two phase synchrony based measures, phase locking value and phase lag index. Finally, these measures were used to characterize the degree of centrality, segregation and integration of the functional brain network. We found that beat frequencies belonging to alpha band produced the most significant steady-state responses across groups. Further, processing of low frequency (delta, theta, alpha) binaural beats had significant impact on cortical network patterns in the alpha band oscillations. Altogether these results provide a neurophysiological account of cortical responses to BB stimulation at varying frequencies, and demonstrate a modulation of cortico-cortical connectivity in musicians' brains, and further suggest a kind of neuronal entrainment of a linear and nonlinear relationship to the beating frequencies.

Virtual milgram: empathic concern or personal distress? Evidence from functional MRI and dispositional measures.

PubMed

Cheetham, Marcus; Pedroni, Andreas F; Antley, Angus; Slater, Mel; Jäncke, Lutz

2009-01-01

One motive for behaving as the agent of another's aggression appears to be anchored in as yet unelucidated mechanisms of obedience to authority. In a recent partial replication of Milgram's obedience paradigm within an immersive virtual environment, participants administered pain to a female virtual human and observed her suffering. Whether the participants' response to the latter was more akin to other-oriented empathic concern for her well-being or to a self-oriented aversive state of personal distress in response to her distress is unclear. Using the stimuli from that study, this event-related fMRI-based study analysed brain activity during observation of the victim in pain versus not in pain. This contrast revealed activation in pre-defined brain areas known to be involved in affective processing but not in those commonly associated with affect sharing (e.g., ACC and insula). We then examined whether different dimensions of dispositional empathy predict activity within the same pre-defined brain regions: While personal distress and fantasy (i.e., tendency to transpose oneself into fictional situations and characters) predicted brain activity, empathic concern and perspective taking predicted no change in neuronal response associated with pain observation. These exploratory findings suggest that there is a distinct pattern of brain activity associated with observing the pain-related behaviour of the victim within the context of this social dilemma, that this observation evoked a self-oriented aversive state of personal distress, and that the objective "reality" of pain is of secondary importance for this response. These findings provide a starting point for experimentally more rigorous investigation of obedience.

Support vector machine learning-based fMRI data group analysis.

PubMed

Wang, Ze; Childress, Anna R; Wang, Jiongjiong; Detre, John A

2007-07-15

To explore the multivariate nature of fMRI data and to consider the inter-subject brain response discrepancies, a multivariate and brain response model-free method is fundamentally required. Two such methods are presented in this paper by integrating a machine learning algorithm, the support vector machine (SVM), and the random effect model. Without any brain response modeling, SVM was used to extract a whole brain spatial discriminance map (SDM), representing the brain response difference between the contrasted experimental conditions. Population inference was then obtained through the random effect analysis (RFX) or permutation testing (PMU) on the individual subjects' SDMs. Applied to arterial spin labeling (ASL) perfusion fMRI data, SDM RFX yielded lower false-positive rates in the null hypothesis test and higher detection sensitivity for synthetic activations with varying cluster size and activation strengths, compared to the univariate general linear model (GLM)-based RFX. For a sensory-motor ASL fMRI study, both SDM RFX and SDM PMU yielded similar activation patterns to GLM RFX and GLM PMU, respectively, but with higher t values and cluster extensions at the same significance level. Capitalizing on the absence of temporal noise correlation in ASL data, this study also incorporated PMU in the individual-level GLM and SVM analyses accompanied by group-level analysis through RFX or group-level PMU. Providing inferences on the probability of being activated or deactivated at each voxel, these individual-level PMU-based group analysis methods can be used to threshold the analysis results of GLM RFX, SDM RFX or SDM PMU.

Genome-Wide Association Study of Dietary Pattern Scores

PubMed Central

Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2017-01-01

Dietary patterns, representing global food supplies rather than specific nutrients or food intakes, have been associated with cardiovascular disease (CVD) incidence and mortality. The contribution of genetic factors in the determination of food intakes, preferences and dietary patterns has been previously established. The current study aimed to identify novel genetic factors associated with reported dietary pattern scores. Reported dietary patterns scores were derived from reported dietary intakes for the preceding month and were obtained through a food frequency questionnaire and genome-wide association study (GWAS) conducted in a study sample of 141 individuals. Reported Prudent and Western dietary patterns demonstrated nominal associations (p < 1 × 10−5) with 78 and 27 single nucleotide polymorphisms (SNPs), respectively. Among these, SNPs annotated to genes previously associated with neurological disorders, CVD risk factors and obesity were identified. Further assessment of SNPs demonstrated an impact on gene expression levels in blood for SNPs located within/near BCKDHB (p = 0.02) and the hypothalamic glucosensor PFKFB3 (p = 0.0004) genes, potentially mediated through an impact on the binding of transcription factors (TFs). Overrepresentations of glucose/energy homeostasis and hormone response TFs were also observed from SNP-surrounding sequences. Results from the current GWAS study suggest an interplay of genes involved in the metabolic response to dietary patterns on obesity, glucose metabolism and food-induced response in the brain in the adoption of dietary patterns. PMID:28644415

Sparse network-based models for patient classification using fMRI

PubMed Central

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

2015-01-01

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

Combined application of BDNF to the eye and brain enhances ganglion cell survival and function in the cat after optic nerve injury.

PubMed

Weber, Arthur J; Viswanáthan, Suresh; Ramanathan, Chidambaram; Harman, Christine D

2010-01-01

To determine whether application of BDNF to the eye and brain provides a greater level of neuroprotection after optic nerve injury than treatment of the eye alone. Retinal ganglion cell survival and pattern electroretinographic responses were compared in normal cat eyes and in eyes that received (1) a mild nerve crush and no treatment, (2) a single intravitreal injection of BDNF at the time of the nerve injury, or (3) intravitreal treatment combined with 1 to 2 weeks of continuous delivery of BDNF to the visual cortex, bilaterally. Relative to no treatment, administration of BDNF to the eye alone resulted in a significant increase in ganglion cell survival at both 1 and 2 weeks after nerve crush (1 week, 79% vs. 55%; 2 weeks, 60% vs. 31%). Combined treatment of the eye and visual cortex resulted in a modest additional increase (17%) in ganglion cell survival in the 1-week eyes, a further significant increase (55%) in the 2-week eyes, and ganglion cell survival levels for both that were comparable to normal (92%-93% survival). Pattern ERG responses for all the treated eyes were comparable to normal at 1 week after injury; however, at 2 weeks, only the responses of eyes receiving the combined BDNF treatment remained so. Although treatment of the eye alone with BDNF has a significant impact on ganglion cell survival after optic nerve injury, combined treatment of the eye and brain may represent an even more effective approach and should be considered in the development of future optic neuropathy-related neuroprotection strategies.

MSG-Evoked c-Fos Activity in the Nucleus of the Solitary Tract Is Dependent upon Fluid Delivery and Stimulation Parameters.

PubMed

Stratford, Jennifer M; Thompson, John A

2016-03-01

The marker of neuronal activation, c-Fos, can be used to visualize spatial patterns of neural activity in response to taste stimulation. Because animals will not voluntarily consume aversive tastes, these stimuli are infused directly into the oral cavity via intraoral cannulae, whereas appetitive stimuli are given in drinking bottles. Differences in these 2 methods make comparison of taste-evoked brain activity between results that utilize these methods problematic. Surprisingly, the intraoral cannulae experimental conditions that produce a similar pattern of c-Fos activity in response to taste stimulation remain unexplored. Stimulation pattern (e.g., constant/intermittent) and hydration state (e.g., water-restricted/hydrated) are the 2 primary differences between delivering tastes via bottles versus intraoral cannulae. Thus, we quantified monosodium glutamate (MSG)-evoked brain activity, as measured by c-Fos, in the nucleus of the solitary tract (nTS; primary taste nucleus) across several conditions. The number and pattern of c-Fos neurons in the nTS of animals that were water-restricted and received a constant infusion of MSG via intraoral cannula most closely mimicked animals that consumed MSG from a bottle. Therefore, in order to compare c-Fos activity between cannulae-stimulated and bottle-stimulated animals, cannulated animals should be water restricted prior to stimulation, and receive taste stimuli at a constant flow. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Electroencephalographic patterns of lithium poisoning: a study of the effect/concentration relationships in the rat.

PubMed

Hanak, Anne-Sophie; Malissin, Isabelle; Poupon, Joël; Risède, Patricia; Chevillard, Lucie; Mégarbane, Bruno

2017-03-01

Lithium overdose may result in encephalopathy and electroencephalographic abnormalities. Three poisoning patterns have been identified based on the ingested dose, previous treatment duration and renal function. Whether the severity of lithium-induced encephalopathy depends on the poisoning pattern has not been established. We designed a rat study to investigate lithium-induced encephalopathy and correlate its severity to plasma, erythrocyte, cerebrospinal fluid and brain lithium concentrations previously determined in rat models mimicking human poisoning patterns. Lithium-induced encephalopathy was assessed and scored using continuous electroencephalography. We demonstrated that lithium overdose was consistently responsible for encephalopathy, the severity of which depended on the poisoning pattern. Acutely poisoned rats developed rapid-onset encephalopathy which reached a maximal grade of 2/5 at 6 h and disappeared at 24 h post-injection. Acute-on-chronically poisoned rats developed persistent and slightly fluctuating encephalopathy which reached a maximal grade of 3/5. Chronically poisoned rats developed rapid-onset but gradually increasing life-threatening encephalopathy which reached a maximal grade of 4/5. None of the acutely, 20% of the acute-on-chronically and 57% of the chronically lithium-poisoned rats developed seizures. The relationships between encephalopathy severity and lithium concentrations fitted a sigmoidal E max model based on cerebrospinal fluid concentrations in acute poisoning and brain concentrations in acute-on-chronic poisoning. In chronic poisoning, worsening of encephalopathy paralleled the increase in plasma lithium concentrations. The severity of lithium-induced encephalopathy is dependent on the poisoning pattern, which was previously shown to determine lithium accumulation in the brain. Our data support the proposition that electroencephalography is a sensitive tool for scoring lithium-related neurotoxicity. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Upregulation of transcription factor NRF2-mediated oxidative stress response pathway in rat brain under short-term chronic hypobaric hypoxia.

PubMed

Sethy, Niroj Kumar; Singh, Manjulata; Kumar, Rajesh; Ilavazhagan, Govindasamy; Bhargava, Kalpana

2011-03-01

Exposure to high altitude (and thus hypobaric hypoxia) induces electrophysiological, metabolic, and morphological modifications in the brain leading to several neurological clinical syndromes. Despite the known fact that hypoxia episodes in brain are a common factor for many neuropathologies, limited information is available on the underlying cellular and molecular mechanisms. In this study, we investigated the temporal effect of short-term (0-12 h) chronic hypobaric hypoxia on global gene expression of rat brain followed by detailed canonical pathway analysis and regulatory network identification. Our analysis revealed significant alteration of 33, 17, 53, 81, and 296 genes (p < 0.05, <1.5-fold) after 0.5, 1, 3, 6, and 12 h of hypoxia, respectively. Biological processes like regulation, metabolic, and transport pathways are temporally activated along with anti- and proinflammatory signaling networks like PI3K/AKT, NF-κB, ERK/MAPK, IL-6 and IL-8 signaling. Irrespective of exposure durations, nuclear factor (erythroid-derived 2)-like 2 (NRF2)-mediated oxidative stress response pathway and genes were detected at all time points suggesting activation of NRF2-ARE antioxidant defense system. The results were further validated by assessing the expression levels of selected genes in temporal as well as brain regions with quantitative RT-PCR and western blot. In conclusion, our whole brain approach with temporal monitoring of gene expression patterns during hypobaric hypoxia has resulted in (1) deciphering sequence of pathways and signaling networks activated during onset of hypoxia, and (2) elucidation of NRF2-orchestrated antioxidant response as a major intrinsic defense mechanism. The results of this study will aid in better understanding and management of hypoxia-induced brain pathologies.

Advances in memory research: single-neuron recordings from the human medial temporal lobe aid our understanding of declarative memory.

PubMed

Viskontas, Indre V

2008-12-01

To gain a complete understanding of how the brain functions, both in illness and good health, data from multiple levels of analysis must be integrated. Technical advances have made direct recordings of neuronal activity deep inside the human brain tractable, providing a rare glimpse into cellular processes during long-term memory formation. Recent findings using intracranial recordings in the medial temporal lobe inform current neural network models of memory, and may lead to a more comprehensive understanding of the neural basis of memory-related processes. These recordings have shown that cells in the hippocampus appear to support declarative learning by distinguishing novel and familiar stimuli via changes in firing patterns. Some cells with highly selective and invariant responses have also been described, and these responses seem to represent abstract concepts such as identity, rather than superficial perceptual features of items. Importantly, however, both selective and globally responsive cells are capable of changing their preferred stimulus depending on the conscious demands of the task. Firing patterns of human medial temporal lobe neurons indicate that cells can be both plastic and stable in terms of the information that they code; although some cells show highly selective and reproducible excitatory responses when presented with a familiar object, other cells change their receptive fields in line with changes in experience and the cognitive environment.

Visual Discomfort From Flash Afterimages of Riloid Patterns.

PubMed

O'Hare, Louise

2017-06-01

Op-art-based stimuli have been shown to be uncomfortable, possibly due to a combination of fixational eye movements (microsaccades) and excessive cortical responses. Efforts have been made to measure illusory phenomena arising from these stimuli in the absence of microsaccades, but there has been no attempt thus far to decouple the effects of the cortical response from the effect of fixational eye movements. This study uses flash afterimages to stabilise the image on the retina and thus reduce the systematic effect of eye movements, in order to investigate the role of the brain in discomfort from op-art-based stimuli. There was a relationship between spatial frequency and the magnitude of the P300 response, showing a similar pattern to that of discomfort judgements, which suggests that there might be a role of discomfort and excessive neural responses independently from the effects of microsaccades.

Greater brain response to emotional expressions of their own children in mothers of preterm infants: an fMRI study.

PubMed

Montirosso, R; Arrigoni, F; Casini, E; Nordio, A; De Carli, P; Di Salle, F; Moriconi, S; Re, M; Reni, G; Borgatti, R

2017-06-01

The birth of a preterm infant and Neonatal Intensive Care Unit hospitalization constitute a potentially traumatic experience for mothers. Although behavioral studies investigated the parenting stress in preterm mothers, no study focused on the underlying neural mechanisms. We examined the effect of preterm births in mothers, by comparing brain activation in mothers of preterm and full-term infants. We used functional magnetic resonance imaging to measure the cerebral response of 10 first-time mothers of preterm infants (gestational age <32 weeks and/or birth weight <1500) and 11 mothers of full-term infants, viewing happy-, neutral- and distress-face images of their own infant, along with a matched unknown infant. While viewing own infant's face preterm mothers showed increased activation in emotional processing area (i.e., inferior frontal gyrus) and social cognition (i.e., supramarginal gyrus) and affiliative behavior (i.e., insula). Differential brain activation patterns in mothers appears to be a function of the atypical parenthood transition related to prematurity.

The diagnosis and treatment of brain metastases in EGFR mutant lung cancer.

PubMed

Minchom, Anna; Yu, Ken C; Bhosle, Jaishree; O'Brien, Mary

2014-05-01

The epidemiology of non-small-cell lung cancer (NSCLC) has changed with a new pattern of disease emerging - a form of adenocarcinoma in mostly younger female patients, who are never or light smokers and more frequently in East Asian populations. Description of EGF receptor (EGFR) mutations has allowed new management strategies to evolve. Oral targeted therapies have broadened the treatment options in the advanced setting with the potential for periods of long term response. The brain is a common site of metastases with EGFR mutated lung cancer typically displaying asymptomatic, small volume, multiple lesions that respond to treatment. We explore the role of local and system therapies for brain metastases in this disease including the role of EGFR inhibitors.

Altruistic behavior: mapping responses in the brain

PubMed Central

Filkowski, Megan M; Cochran, R Nick; Haas, Brian W

2016-01-01

Altruism is an important social construct related to human relationships and the way many interpersonal and economic decisions are made. Recent progress in social neuroscience research shows that altruism is associated with a specific pattern of brain activity. The tendency to engage in altruistic behaviors is associated with greater activity within limbic regions such as the nucleus accumbens and anterior cingulate cortex in addition to cortical regions such as the medial prefrontal cortex and temporoparietal junction. Here, we review existing theoretical models of altruism as well as recent empirical neuroimaging research demonstrating how altruism is processed within the brain. This review not only highlights the progress in neuroscience research on altruism but also shows that there exist several open questions that remain unexplored. PMID:28580317

Kernel-Based Relevance Analysis with Enhanced Interpretability for Detection of Brain Activity Patterns

PubMed Central

Alvarez-Meza, Andres M.; Orozco-Gutierrez, Alvaro; Castellanos-Dominguez, German

2017-01-01

We introduce Enhanced Kernel-based Relevance Analysis (EKRA) that aims to support the automatic identification of brain activity patterns using electroencephalographic recordings. EKRA is a data-driven strategy that incorporates two kernel functions to take advantage of the available joint information, associating neural responses to a given stimulus condition. Regarding this, a Centered Kernel Alignment functional is adjusted to learning the linear projection that best discriminates the input feature set, optimizing the required free parameters automatically. Our approach is carried out in two scenarios: (i) feature selection by computing a relevance vector from extracted neural features to facilitating the physiological interpretation of a given brain activity task, and (ii) enhanced feature selection to perform an additional transformation of relevant features aiming to improve the overall identification accuracy. Accordingly, we provide an alternative feature relevance analysis strategy that allows improving the system performance while favoring the data interpretability. For the validation purpose, EKRA is tested in two well-known tasks of brain activity: motor imagery discrimination and epileptic seizure detection. The obtained results show that the EKRA approach estimates a relevant representation space extracted from the provided supervised information, emphasizing the salient input features. As a result, our proposal outperforms the state-of-the-art methods regarding brain activity discrimination accuracy with the benefit of enhanced physiological interpretation about the task at hand. PMID:29056897

Brain response to empathy-eliciting scenarios involving pain in incarcerated psychopaths

PubMed Central

Decety, Jean; Skelly, Laurie R.; Kiehl, Kent A.

2013-01-01

Context A marked lack of empathy is a hallmark characteristic of individuals with psychopathy. However, neural response associated to empathic processing has not yet been directly examined in psychopathy especially in response to the perception of other people in pain and distress. Objective To identify potential differences in patterns of neural activity in incarcerated psychopaths and incarcerated controls during the perception of empathy-eliciting stimuli depicting other people in pain. Design In a case-control study, brain activation patterns elicited by dynamic stimuli depicting individuals being harmed and facial expression of pain were compared between incarcerated psychopaths and incarcerated controls. Setting Participants were scanned in on the grounds of a correctional facility using the Mind Research Network's mobile 1.5 T MRI system. Participants Eighty incarcerated males were classified according to scores on the Hare Psychopathy Checklist-Revised (PCL-R) as high (n = 27; PCL-R =30), intermediate (n = 28; PCL-R between 21–29), or low (n = 25; PCL-R ≤20) on psychopathy. Main Outcome Measure Neuro-hemodynamic response to empathy-eliciting dynamic scenarios revealed by functional magnetic resonance imaging. Results Psychopaths exhibited significantly less activation in the ventromedial prefrontal cortex, lateral orbitofrontal cortex, and periaqueductal gray relative to controls, but showed greater activation in the insula. Conclusion In response to pain cues expressed by others, psychopaths exhibit deficits in vmPFC and OFC regardless of stimulus type, but display selective impairment in processing facial cues of distress in regions associated with cognitive mentalizing. PMID:23615636

The hemodynamic changes in the human prefrontal cortex during the Flanker and Simon tasks: a fNIRS study

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Lin, Xiaohong

2016-03-01

Functional near-infrared spectroscopy (fNIRS) is a low-cost, portable and noninvasive functional neuroimaging technique by measuring the change in the concentrations of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR). The aim of present study is to reveal the different brain activity pattern of adult subjects during the completion of flanker and Simon tasks underlying the congruent and incongruent test conditions so as to identify the basic neural mechanism of inhibitory control in executive function. In the study, we utilized fNIRS to explore the hemodynamic changes in the prefrontal cortex and our imaging results suggested that there were notable differences for the hemodynamic responses between the flank and Simon task. A striking difference is that for the flank task, the increase in the HbO concentration during incongruent trials was larger than that during congruent trials for the channels across middle frontal cortex while for the Simon task, the hemodynamic response was stronger for the congruent condition compared to that from the incongruent one. Interestingly, the hemodynamic response exhibited similar task-related activation in the superior frontal cortex for both the congruent and incongruent conditions. Further, independent component analysis showed that different brain activation patterns were identified to accomplish different inhibitory control tasks underlying the congruent and incongruent conditions.

Unique and shared inflammatory profiles of human brain endothelia and pericytes.

PubMed

Smyth, Leon C D; Rustenhoven, Justin; Park, Thomas I-H; Schweder, Patrick; Jansson, Deidre; Heppner, Peter A; O'Carroll, Simon J; Mee, Edward W; Faull, Richard L M; Curtis, Maurice; Dragunow, Mike

2018-05-11

Pericytes and endothelial cells are critical cellular components of the blood-brain barrier (BBB) and play an important role in neuroinflammation. To date, the majority of inflammation-related studies in endothelia and pericytes have been carried out using immortalised cell lines or non-human-derived cells. Whether these are representative of primary human cells is unclear and systematic comparisons of the inflammatory responses of primary human brain-derived pericytes and endothelia has yet to be performed. To study the effects of neuroinflammation at the BBB, primary brain endothelial cells and pericytes were isolated from human biopsy tissue. Culture purity was examined using qPCR and immunocytochemistry. Electrical cell-substrate impedance sensing (ECIS) was used to determine the barrier properties of endothelial and pericyte cultures. Using immunocytochemistry, cytometric bead array, and ECIS, we compared the responses of endothelia and pericytes to a panel of inflammatory stimuli (IL-1β, TNFα, LPS, IFN-γ, TGF-β 1 , IL-6, and IL-4). Secretome analysis was performed to identify unique secretions of endothelia and pericytes in response to IL-1β. Endothelial cells were pure, moderately proliferative, retained the expression of BBB-related junctional proteins and transporters, and generated robust TEER. Both endothelia and pericytes have the same pattern of transcription factor activation in response to inflammatory stimuli but respond differently at the secretion level. Secretome analysis confirmed that endothelia and pericytes have overlapping but distinct secretome profiles in response to IL-1β. We identified several cell-type specific responses, including G-CSF and GM-CSF (endothelial-specific), and IGFBP2 and IGFBP3 (pericyte-specific). Finally, we demonstrated that direct addition of IL-1β, TNFα, LPS, and IL-4 contributed to the loss of endothelial barrier integrity in vitro. Here, we identify important cell-type differences in the inflammatory response of brain pericytes and endothelia and provide, for the first time, a comprehensive profile of the secretions of primary human brain endothelia and pericytes which has implications for understanding how inflammation affects the cerebrovasculature.

Multivariate pattern analysis of fMRI: the early beginnings.

PubMed

Haxby, James V

2012-08-15

In 2001, we published a paper on the representation of faces and objects in ventral temporal cortex that introduced a new method for fMRI analysis, which subsequently came to be called multivariate pattern analysis (MVPA). MVPA now refers to a diverse set of methods that analyze neural responses as patterns of activity that reflect the varying brain states that a cortical field or system can produce. This paper recounts the circumstances and events that led to the original study and later developments and innovations that have greatly expanded this approach to fMRI data analysis, leading to its widespread application. Copyright © 2012 Elsevier Inc. All rights reserved.

A Statistically Representative Atlas for Mapping Neuronal Circuits in the Drosophila Adult Brain.

PubMed

Arganda-Carreras, Ignacio; Manoliu, Tudor; Mazuras, Nicolas; Schulze, Florian; Iglesias, Juan E; Bühler, Katja; Jenett, Arnim; Rouyer, François; Andrey, Philippe

2018-01-01

Imaging the expression patterns of reporter constructs is a powerful tool to dissect the neuronal circuits of perception and behavior in the adult brain of Drosophila , one of the major models for studying brain functions. To date, several Drosophila brain templates and digital atlases have been built to automatically analyze and compare collections of expression pattern images. However, there has been no systematic comparison of performances between alternative atlasing strategies and registration algorithms. Here, we objectively evaluated the performance of different strategies for building adult Drosophila brain templates and atlases. In addition, we used state-of-the-art registration algorithms to generate a new group-wise inter-sex atlas. Our results highlight the benefit of statistical atlases over individual ones and show that the newly proposed inter-sex atlas outperformed existing solutions for automated registration and annotation of expression patterns. Over 3,000 images from the Janelia Farm FlyLight collection were registered using the proposed strategy. These registered expression patterns can be searched and compared with a new version of the BrainBaseWeb system and BrainGazer software. We illustrate the validity of our methodology and brain atlas with registration-based predictions of expression patterns in a subset of clock neurons. The described registration framework should benefit to brain studies in Drosophila and other insect species.

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

Rat astrocytes during anoxia: Secretome profile of cytokines and chemokines.

PubMed

Samy, Zeinab Adel; Al-Abdullah, Lulwa; Turcani, Marian; Craik, James; Redzic, Zoran

2018-06-04

The precise mechanisms of the inflammatory responses after cerebral ischemia in vivo are difficult to elucidate because of the complex nature of multiple series of interactions between cells and molecules. This study explored temporal patterns of secretion of 30 cytokines and chemokines from Sprague Dawley rat astrocytes in primary culture in order to elucidate signaling pathways that are triggered by astrocytes during anoxia. Primary cultures of rat brain astrocytes were incubated for periods of 2-24 hr in the absence of oxygen (anoxia) or under normal partial pressure of oxygen (controls). Simultaneous detection of 29 cytokines and chemokines in the samples was performed using a rat cytokine array panel, while the temporal pattern of angiopoietin-1 (Ang-1) secretion was determined separately using ELISA. Wilcoxon-Mann-Whitney test was used to compare normoxic and anoxic samples and the Hodge-Lehman estimator with exact 95% confidence intervals was computed to assess the size of differences in cytokine secretion. The obtained data were imported into the Core Analysis tool of Ingenuity Pathways Analysis software in order to relate changes in secretion of cytokines and chemokines from astrocytes during anoxia to potential molecular signal networks. With the exception of Ang-1, concentrations of all cytokines/chemokines in samples collected after anoxia exposure were either the same, or higher, than in control groups. No clear pattern of changes could be established for groups of cytokines with similar effects (i.e., pro- or anti-inflammatory cytokines). The pattern of changes in cytokine secretion during anoxia was associated with the HIF-1α-mediated response, as well as cytokines IL-1β and cathepsin S pathways, which are related to initiation of inflammation and antigen presentation, respectively, and to ciliary neurotrophic factor. These in vitro findings suggest that astrocytes may play a role in triggering inflammation during anoxia/ischemia of the brain. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Normothermic Mouse Functional MRI of Acute Focal Thermostimulation for Probing Nociception

PubMed Central

Reimann, Henning Matthias; Hentschel, Jan; Marek, Jaroslav; Huelnhagen, Till; Todiras, Mihail; Kox, Stefanie; Waiczies, Sonia; Hodge, Russ; Bader, Michael; Pohlmann, Andreas; Niendorf, Thoralf

2016-01-01

Combining mouse genomics and functional magnetic resonance imaging (fMRI) provides a promising tool to unravel the molecular mechanisms of chronic pain. Probing murine nociception via the blood oxygenation level-dependent (BOLD) effect is still challenging due to methodological constraints. Here we report on the reproducible application of acute noxious heat stimuli to examine the feasibility and limitations of functional brain mapping for central pain processing in mice. Recent technical and procedural advances were applied for enhanced BOLD signal detection and a tight control of physiological parameters. The latter includes the development of a novel mouse cradle designed to maintain whole-body normothermia in anesthetized mice during fMRI in a way that reflects the thermal status of awake, resting mice. Applying mild noxious heat stimuli to wildtype mice resulted in highly significant BOLD patterns in anatomical brain structures forming the pain matrix, which comprise temporal signal intensity changes of up to 6% magnitude. We also observed sub-threshold correlation patterns in large areas of the brain, as well as alterations in mean arterial blood pressure (MABP) in response to the applied stimulus. PMID:26821826

Diode probes for spatiotemporal optical control of multiple neurons in freely moving animals

PubMed Central

Koos, Tibor; Buzsáki, György

2012-01-01

Neuronal control with high temporal precision is possible with optogenetics, yet currently available methods do not enable to control independently multiple locations in the brains of freely moving animals. Here, we describe a diode-probe system that allows real-time and location-specific control of neuronal activity at multiple sites. Manipulation of neuronal activity in arbitrary spatiotemporal patterns is achieved by means of an optoelectronic array, manufactured by attaching multiple diode-fiber assemblies to high-density silicon probes or wire tetrodes and implanted into the brains of animals that are expressing light-responsive opsins. Each diode can be controlled separately, allowing localized light stimulation of neuronal activators and silencers in any temporal configuration and concurrent recording of the stimulated neurons. Because the only connections to the animals are via a highly flexible wire cable, unimpeded behavior is allowed for circuit monitoring and multisite perturbations in the intact brain. The capacity of the system to generate unique neural activity patterns facilitates multisite manipulation of neural circuits in a closed-loop manner and opens the door to addressing novel questions. PMID:22496529

Normothermic Mouse Functional MRI of Acute Focal Thermostimulation for Probing Nociception

NASA Astrophysics Data System (ADS)

Reimann, Henning Matthias; Hentschel, Jan; Marek, Jaroslav; Huelnhagen, Till; Todiras, Mihail; Kox, Stefanie; Waiczies, Sonia; Hodge, Russ; Bader, Michael; Pohlmann, Andreas; Niendorf, Thoralf

2016-01-01

Combining mouse genomics and functional magnetic resonance imaging (fMRI) provides a promising tool to unravel the molecular mechanisms of chronic pain. Probing murine nociception via the blood oxygenation level-dependent (BOLD) effect is still challenging due to methodological constraints. Here we report on the reproducible application of acute noxious heat stimuli to examine the feasibility and limitations of functional brain mapping for central pain processing in mice. Recent technical and procedural advances were applied for enhanced BOLD signal detection and a tight control of physiological parameters. The latter includes the development of a novel mouse cradle designed to maintain whole-body normothermia in anesthetized mice during fMRI in a way that reflects the thermal status of awake, resting mice. Applying mild noxious heat stimuli to wildtype mice resulted in highly significant BOLD patterns in anatomical brain structures forming the pain matrix, which comprise temporal signal intensity changes of up to 6% magnitude. We also observed sub-threshold correlation patterns in large areas of the brain, as well as alterations in mean arterial blood pressure (MABP) in response to the applied stimulus.

Distributed and opposing effects of incidental learning in the human brain.

PubMed

Hall, Michelle G; Naughtin, Claire K; Mattingley, Jason B; Dux, Paul E

2018-06-01

Incidental learning affords a behavioural advantage when sensory information matches regularities that have previously been encountered. Previous studies have taken a focused approach by probing the involvement of specific candidate brain regions underlying incidentally acquired memory representations, as well as expectation effects on early sensory representations. Here, we investigated the broader extent of the brain's sensitivity to violations and fulfilments of expectations, using an incidental learning paradigm in which the contingencies between target locations and target identities were manipulated without participants' overt knowledge. Multivariate analysis of functional magnetic resonance imaging data was applied to compare the consistency of neural activity for visual events that the contingency manipulation rendered likely versus unlikely. We observed widespread sensitivity to expectations across frontal, temporal, occipital, and sub-cortical areas. These activation clusters showed distinct response profiles, such that some regions displayed more reliable activation patterns under fulfilled expectations, whereas others showed more reliable patterns when expectations were violated. These findings reveal that expectations affect multiple stages of information processing during visual decision making, rather than early sensory processing stages alone. Copyright © 2018 Elsevier Inc. All rights reserved.

Feature extraction inspired by V1 in visual cortex

NASA Astrophysics Data System (ADS)

Lv, Chao; Xu, Yuelei; Zhang, Xulei; Ma, Shiping; Li, Shuai; Xin, Peng; Zhu, Mingning; Ma, Hongqiang

2018-04-01

Target feature extraction plays an important role in pattern recognition. It is the most complicated activity in the brain mechanism of biological vision. Inspired by high properties of primary visual cortex (V1) in extracting dynamic and static features, a visual perception model was raised. Firstly, 28 spatial-temporal filters with different orientations, half-squaring operation and divisive normalization were adopted to obtain the responses of V1 simple cells; then, an adjustable parameter was added to the output weight so that the response of complex cells was got. Experimental results indicate that the proposed V1 model can perceive motion information well. Besides, it has a good edge detection capability. The model inspired by V1 has good performance in feature extraction and effectively combines brain-inspired intelligence with computer vision.

Test-retest assessment of cortical activation induced by repetitive transcranial magnetic stimulation with brain atlas-guided optical topography

NASA Astrophysics Data System (ADS)

Tian, Fenghua; Kozel, F. Andrew; Yennu, Amarnath; Croarkin, Paul E.; McClintock, Shawn M.; Mapes, Kimberly S.; Husain, Mustafa M.; Liu, Hanli

2012-11-01

Repetitive transcranial magnetic stimulation (rTMS) is a technology that stimulates neurons with rapidly changing magnetic pulses with demonstrated therapeutic applications for various neuropsychiatric disorders. Functional near-infrared spectroscopy (fNIRS) is a suitable tool to assess rTMS-evoked brain responses without interference from the magnetic or electric fields generated by the TMS coil. We have previously reported a channel-wise study of combined rTMS/fNIRS on the motor and prefrontal cortices, showing a robust decrease of oxygenated hemoglobin concentration (Δ[HbO2]) at the sites of 1-Hz rTMS and the contralateral brain regions. However, the reliability of this putative clinical tool is unknown. In this study, we develop a rapid optical topography approach to spatially characterize the rTMS-evoked hemodynamic responses on a standard brain atlas. A hemispherical approximation of the brain is employed to convert the three-dimensional topography on the complex brain surface to a two-dimensional topography in the spherical coordinate system. The test-retest reliability of the combined rTMS/fNIRS is assessed using repeated measurements performed two to three days apart. The results demonstrate that the Δ[HbO2] amplitudes have moderate-to-high reliability at the group level; and the spatial patterns of the topographic images have high reproducibility in size and a moderate degree of overlap at the individual level.

Role of heat shock protein Hsp25 in the response of the orofacial nuclei motor system to physiological stress

NASA Technical Reports Server (NTRS)

Murashov, A. K.; Talebian, S.; Wolgemuth, D. J.

1998-01-01

Although expression of the small heat shock protein family member Hsp25 has been previously observed in the central nervous system (CNS), both constitutively and upon induction, its function in the CNS remains far from clear. In the present study we have characterized the spatial pattern of expression of Hsp25 in the normal adult mouse brain as well as the changes in expression patterns induced by subjecting mice to experimental hyperthermia or hypoxia. Immunohistochemical analysis revealed a surprisingly restricted pattern of constitutive expression of Hsp25 in the brain, limited to the facial, trigeminal, ambiguus, hypoglossal and vagal motor nuclei of the brainstem. After hyperthermia or hypoxia treatment, significant increases in the levels of Hsp25 were observed in these same areas and also in fibers of the facial and trigeminal nerve tracts. Immunoblot analysis of protein lysates from brainstem also showed the same pattern of induction of Hsp25. Surprisingly, no other area in the brain showed expression of Hsp25, in either control or stressed animals. The highly restricted expression of Hsp25 implies that this protein may have a specific physiological role in the orofacial motor nuclei, which govern precise coordination between muscles of mastication and the pharynx, larynx, and face. Its rapid induction after stress further suggests that Hsp25 may serve as a specific molecular chaperone in the lower cholinergic motor neurons and along their fibers under conditions of stress or injury. Copyright 1998 Elsevier Science B.V.

Cortical activation patterns to spatially presented pure tone stimuli with different intensities measured by functional near-infrared spectroscopy.

PubMed

Bauernfeind, Günther; Wriessnegger, Selina C; Haumann, Sabine; Lenarz, Thomas

2018-03-08

Functional near-infrared spectroscopy (fNIRS) is an emerging technique for the assessment of functional activity of the cerebral cortex. Recently fNIRS was also envisaged as a novel neuroimaging approach for measuring the auditory cortex activity in the field of in auditory diagnostics. This study aimed to investigate differences in brain activity related to spatially presented sounds with different intensities in 10 subjects by means of functional near-infrared spectroscopy (fNIRS). We found pronounced cortical activation patterns in the temporal and frontal regions of both hemispheres. In contrast to these activation patterns, we found deactivation patterns in central and parietal regions of both hemispheres. Furthermore our results showed an influence of spatial presentation and intensity of the presented sounds on brain activity in related regions of interest. These findings are in line with previous fMRI studies which also reported systematic changes of activation in temporal and frontal areas with increasing sound intensity. Although clear evidence for contralaterality effects and hemispheric asymmetries were absent in the group data, these effects were partially visible on the single subject level. Concluding, fNIRS is sensitive enough to capture differences in brain responses during the spatial presentation of sounds with different intensities in several cortical regions. Our results may serve as a valuable contribution for further basic research and the future use of fNIRS in the area of central auditory diagnostics. © 2018 Wiley Periodicals, Inc.

Comparative functional neuroanatomy between implicit and explicit memory tasks under negative emotional condition in schizophrenia.

PubMed

Song, Xiao-Li; Kim, Gwang-Won; Moon, Chung-Man; Jeong, Gwang-Woo

To evaluate the brain activation patterns in response to negative emotion during implicit and explicit memory in patients with schizophrenia. Fourteen patients with schizophrenia and 14 healthy controls were included in this study. The 3.0T fMRI was obtained while the subjects performed the implicit and explicit retrievals with unpleasant words. The different predominant brain activation areas were observed during the implicit retrieval and explicit with unpleasant words. The differential neural mechanisms between implicit and explicit memory tasks associated with negative emotional processing in schizophrenia. Copyright © 2017. Published by Elsevier Inc.

Model for the computation of self-motion in biological systems

NASA Technical Reports Server (NTRS)

Perrone, John A.

1992-01-01

A technique is presented by which direction- and speed-tuned cells, such as those commonly found in the middle temporal region of the primate brain, can be utilized to analyze the patterns of retinal image motion that are generated during observer movement through the environment. The developed model determines heading by finding the peak response in a population of detectors or neurons each tuned to a particular heading direction. It is suggested that a complex interaction of multiple cell networks is required for the solution of the self-motion problem in the primate brain.

Transprocessing: A Proposed Neurobiological Mechanism of Psychotherapeutic Processing

PubMed Central

Bota, Robert G.

2014-01-01

How does the human brain absorb information and turn it into skills of its own in psychotherapy? In an attempt to answer this question, the authors will review the intricacies of processing channels in psychotherapy and propose the term transprocessing (as in transduction and processing combined) for the underlying mechanisms. Through transprocessing the brain processes multimodal memories and creates reparative solutions in the course of psychotherapy. Transprocessing is proposed as a stage-sequenced mechanism of deconstruction of engrained patterns of response. Through psychotherapy, emotional-cognitive reintegration and its consolidation is accomplished. This process is mediated by cellular and neural plasticity changes. PMID:25478135

Contralateral Disconnection of the Rat Prelimbic Cortex and Dorsomedial Striatum Impairs Cue-Guided Behavioral Switching

ERIC Educational Resources Information Center

Baker, Phillip M.; Ragozzino, Michael E.

2014-01-01

Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for…

Improved Volitional Recall of Motor-Imagery-Related Brain Activation Patterns Using Real-Time Functional MRI-Based Neurofeedback.

PubMed

Bagarinao, Epifanio; Yoshida, Akihiro; Ueno, Mika; Terabe, Kazunori; Kato, Shohei; Isoda, Haruo; Nakai, Toshiharu

2018-01-01

Motor imagery (MI), a covert cognitive process where an action is mentally simulated but not actually performed, could be used as an effective neurorehabilitation tool for motor function improvement or recovery. Recent approaches employing brain-computer/brain-machine interfaces to provide online feedback of the MI during rehabilitation training have promising rehabilitation outcomes. In this study, we examined whether participants could volitionally recall MI-related brain activation patterns when guided using neurofeedback (NF) during training. The participants' performance was compared to that without NF. We hypothesized that participants would be able to consistently generate the relevant activation pattern associated with the MI task during training with NF compared to that without NF. To assess activation consistency, we used the performance of classifiers trained to discriminate MI-related brain activation patterns. Our results showed significantly higher predictive values of MI-related activation patterns during training with NF. Additionally, this improvement in the classification performance tends to be associated with the activation of middle temporal gyrus/inferior occipital gyrus, a region associated with visual motion processing, suggesting the importance of performance monitoring during MI task training. Taken together, these findings suggest that the efficacy of MI training, in terms of generating consistent brain activation patterns relevant to the task, can be enhanced by using NF as a mechanism to enable participants to volitionally recall task-related brain activation patterns.

[Magnetic resonance spectroscopy of metabolic changes in mice brain after 2-deoxy-D-glucose injection].

PubMed

Moshkin, M P; Akulov, A E; Petrovskiĭ, D V; Saĭk, O V; Petrovskiĭ, E D; Savelov, A A; Koptug, I V

2012-10-01

In vivo proton magnetic resonance spectroscopy (1H MRS) of ICR male mice was used to study the brain (hippocampus) metabolic response to the acute deficiency of the available energy or to the pro-inflammatory stimulus. Inhibition of glycolysis by means of an intraperitoneal injection with 2-deoxy-D-glucose (2DG) reduced the levels of gamma-aminobutiric acid (GABA), N-acetylaspartate (NAA) and choline compounds, and at the same time increased the levels of glutamate and glutamine. An opposite effect was found after injection with bacterial lipopolysaccharide (LPS)--a very common pro-inflammatory inducer. An increase in the amounts of GABA, NAA and choline compounds in the brain occurred three hours after the injection of LPS. Different metabolic responses to the energy deficiency and the pro-inflammatory stimuli can explain the contradictory results of the brain MRS studies under neurodegenerative pathology, which is accompanied by both mitochondrial dysfunction and inflammation. Prevalence of the excitatory metabolites such as glutamate and glutamine in 2DG treated mice is in good agreement with excitation observed during temporary reduction of the available energy under acute hypoxia or starvation. In turn, LPS, as an inducer of the sickness behavior, shifts brain metabolic pattern to prevalence of the inhibitory neurotransmitter GABA.

The Neuropeptide Y (NPY)-ergic System is Associated with Behavioral Resilience to Stress Exposure in an Animal Model of Post-Traumatic Stress Disorder

PubMed Central

Cohen, Hagit; Liu, Tianmin; Kozlovsky, Nitsan; Kaplan, Zeev; Zohar, Joseph; Mathé, Aleksander A

2012-01-01

Converging evidence implicates the regulatory neuropeptide Y (NPY) in anxiety- and depression-related behaviors. The present study sought to assess whether there is an association between the magnitude of behavioral responses to stress and patterns of NPY in selected brain areas, and subsequently, whether pharmacological manipulations of NPY levels affect behavior in an animal model of PTSD. Animals were exposed to predator-scent stress for 15 min. Behaviors were assessed with the elevated plus maze and acoustic startle response tests 7 days later. Preset cutoff criteria classified exposed animals according to their individual behavioral responses. NPY protein levels were assessed in specific brain regions 8 days after the exposure. The behavioral effects of NPY agonist, NPY-Y1-receptor antagonist, or placebo administered centrally 1 h post-exposure were evaluated in the same manner. Immunohistochemical technique was used to detect the expression of the NPY, NPY-Y1 receptor, brain-derived neurotrophic factor, and GR 1 day after the behavioral tests. Animals whose behavior was extremely disrupted (EBR) selectively displayed significant downregulation of NPY in the hippocampus, periaqueductal gray, and amygdala, compared with animals whose behavior was minimally (MBR) or partially (PBR) disrupted, and with unexposed controls. One-hour post-exposure treatment with NPY significantly reduced prevalence rates of EBR and reduced trauma-cue freezing responses, compared with vehicle controls. The distinctive pattern of NPY downregulation that correlated with EBR as well as the resounding behavioral effects of pharmacological manipulation of NPY indicates an intimate association between NPY and behavioral responses to stress, and potentially between molecular and psychopathological processes, which underlie the observed changes in behavior. The protective qualities attributed to NPY are supported by the extreme reduction of its expression in animals severely affected by the stressor and imply a role in promoting resilience and/or recovery. PMID:21976046

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

PubMed

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

2018-01-01

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

Distinct fMRI Responses to Self-Induced versus Stimulus Motion during Free Viewing in the Macaque

PubMed Central

Kaneko, Takaaki; Saleem, Kadharbatcha S.; Berman, Rebecca A.; Leopold, David A.

2016-01-01

Visual motion responses in the brain are shaped by two distinct sources: the physical movement of objects in the environment and motion resulting from one's own actions. The latter source, termed visual reafference, stems from movements of the head and body, and in primates from the frequent saccadic eye movements that mark natural vision. To study the relative contribution of reafferent and stimulus motion during natural vision, we measured fMRI activity in the brains of two macaques as they freely viewed >50 hours of naturalistic video footage depicting dynamic social interactions. We used eye movements obtained during scanning to estimate the level of reafferent retinal motion at each moment in time. We also estimated the net stimulus motion by analyzing the video content during the same time periods. Mapping the responses to these distinct sources of retinal motion, we found a striking dissociation in the distribution of visual responses throughout the brain. Reafferent motion drove fMRI activity in the early retinotopic areas V1, V2, V3, and V4, particularly in their central visual field representations, as well as lateral aspects of the caudal inferotemporal cortex (area TEO). However, stimulus motion dominated fMRI responses in the superior temporal sulcus, including areas MT, MST, and FST as well as more rostral areas. We discuss this pronounced separation of motion processing in the context of natural vision, saccadic suppression, and the brain's utilization of corollary discharge signals. SIGNIFICANCE STATEMENT Visual motion arises not only from events in the external world, but also from the movements of the observer. For example, even if objects are stationary in the world, the act of walking through a room or shifting one's eyes causes motion on the retina. This “reafferent” motion propagates into the brain as signals that must be interpreted in the context of real object motion. The delineation of whole-brain responses to stimulus versus self-generated retinal motion signals is critical for understanding visual perception and is of pragmatic importance given the increasing use of naturalistic viewing paradigms. The present study uses fMRI to demonstrate that the brain exhibits a fundamentally different pattern of responses to these two sources of retinal motion. PMID:27629710

Distinct fMRI Responses to Self-Induced versus Stimulus Motion during Free Viewing in the Macaque.

PubMed

Russ, Brian E; Kaneko, Takaaki; Saleem, Kadharbatcha S; Berman, Rebecca A; Leopold, David A

2016-09-14

Visual motion responses in the brain are shaped by two distinct sources: the physical movement of objects in the environment and motion resulting from one's own actions. The latter source, termed visual reafference, stems from movements of the head and body, and in primates from the frequent saccadic eye movements that mark natural vision. To study the relative contribution of reafferent and stimulus motion during natural vision, we measured fMRI activity in the brains of two macaques as they freely viewed >50 hours of naturalistic video footage depicting dynamic social interactions. We used eye movements obtained during scanning to estimate the level of reafferent retinal motion at each moment in time. We also estimated the net stimulus motion by analyzing the video content during the same time periods. Mapping the responses to these distinct sources of retinal motion, we found a striking dissociation in the distribution of visual responses throughout the brain. Reafferent motion drove fMRI activity in the early retinotopic areas V1, V2, V3, and V4, particularly in their central visual field representations, as well as lateral aspects of the caudal inferotemporal cortex (area TEO). However, stimulus motion dominated fMRI responses in the superior temporal sulcus, including areas MT, MST, and FST as well as more rostral areas. We discuss this pronounced separation of motion processing in the context of natural vision, saccadic suppression, and the brain's utilization of corollary discharge signals. Visual motion arises not only from events in the external world, but also from the movements of the observer. For example, even if objects are stationary in the world, the act of walking through a room or shifting one's eyes causes motion on the retina. This "reafferent" motion propagates into the brain as signals that must be interpreted in the context of real object motion. The delineation of whole-brain responses to stimulus versus self-generated retinal motion signals is critical for understanding visual perception and is of pragmatic importance given the increasing use of naturalistic viewing paradigms. The present study uses fMRI to demonstrate that the brain exhibits a fundamentally different pattern of responses to these two sources of retinal motion. Copyright © 2016 the authors 0270-6474/16/369580-10$15.00/0.

TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke.

PubMed

Doyle, Kristian P; Cekanaviciute, Egle; Mamer, Lauren E; Buckwalter, Marion S

2010-10-11

TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging. We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia. TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes. We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial scar formation and the immune response to stroke.

Revealing the cerebral regions and networks mediating vulnerability to depression: oxidative metabolism mapping of rat brain.

PubMed

Harro, Jaanus; Kanarik, Margus; Kaart, Tanel; Matrov, Denis; Kõiv, Kadri; Mällo, Tanel; Del Río, Joaquin; Tordera, Rosa M; Ramirez, Maria J

2014-07-01

The large variety of available animal models has revealed much on the neurobiology of depression, but each model appears as specific to a significant extent, and distinction between stress response, pathogenesis of depression and underlying vulnerability is difficult to make. Evidence from epidemiological studies suggests that depression occurs in biologically predisposed subjects under impact of adverse life events. We applied the diathesis-stress concept to reveal brain regions and functional networks that mediate vulnerability to depression and response to chronic stress by collapsing data on cerebral long term neuronal activity as measured by cytochrome c oxidase histochemistry in distinct animal models. Rats were rendered vulnerable to depression either by partial serotonergic lesion or by maternal deprivation, or selected for a vulnerable phenotype (low positive affect, low novelty-related activity or high hedonic response). Environmental adversity was brought about by applying chronic variable stress or chronic social defeat. Several brain regions, most significantly median raphe, habenula, retrosplenial cortex and reticular thalamus, were universally implicated in long-term metabolic stress response, vulnerability to depression, or both. Vulnerability was associated with higher oxidative metabolism levels as compared to resilience to chronic stress. Chronic stress, in contrast, had three distinct patterns of effect on oxidative metabolism in vulnerable vs. resilient animals. In general, associations between regional activities in several brain circuits were strongest in vulnerable animals, and chronic stress disrupted this interrelatedness. These findings highlight networks that underlie resilience to stress, and the distinct response to stress that occurs in vulnerable subjects. Copyright © 2014 Elsevier B.V. All rights reserved.

Patterns of differences in brain morphology in humans as compared to extant apes.

PubMed

Aldridge, Kristina

2011-01-01

Although human evolution is characterized by a vast increase in brain size, it is not clear whether or not certain regions of the brain are enlarged disproportionately in humans, or how this enlargement relates to differences in overall neural morphology. The aim of this study is to determine whether or not there are specific suites of features that distinguish the morphology of the human brain from that of apes. The study sample consists of whole brain, in vivo magnetic resonance images (MRIs) of anatomically modern humans (Homo sapiens sapiens) and five ape species (gibbons, orangutans, gorillas, chimpanzees, bonobos). Twenty-nine 3D landmarks, including surface and internal features of the brain were located on 3D MRI reconstructions of each individual using MEASURE software. Landmark coordinate data were scaled for differences in size and analyzed using Euclidean Distance Matrix Analysis (EDMA) to statistically compare the brains of each non-human ape species to the human sample. Results of analyses show both a pattern of brain morphology that is consistently different between all apes and humans, as well as patterns that differ among species. Further, both the consistent and species-specific patterns include cortical and subcortical features. The pattern that remains consistent across species indicates a morphological reorganization of 1) relationships between cortical and subcortical frontal structures, 2) expansion of the temporal lobe and location of the amygdala, and 3) expansion of the anterior parietal region. Additionally, results demonstrate that, although there is a pattern of morphology that uniquely defines the human brain, there are also patterns that uniquely differentiate human morphology from the morphology of each non-human ape species, indicating that reorganization of neural morphology occurred at the evolutionary divergence of each of these groups. Copyright © 2010 Elsevier Ltd. All rights reserved.

Patterns of differences in brain morphology in humans as compared to extant apes

PubMed Central

Aldridge, Kristina

2010-01-01

Although human evolution is characterized by a vast increase in brain size, it is not clear whether or not certain regions of the brain are enlarged disproportionately in humans, or how this enlargement relates to differences in overall neural morphology. The aim of this study is to determine whether or not there are specific suites of features that distinguish the morphology of the human brain from that of apes. The study sample consists of whole brain, in vivo magnetic resonance images (MRIs) of anatomically modern humans (Homo sapiens sapiens) and five ape species (gibbons, orangutans, gorillas, chimpanzees, bonobos). Twenty-nine 3D landmarks, including surface and internal features of the brain were located on 3D MRI reconstructions of each individual using MEASURE software. Landmark coordinate data were scaled for differences in size and analyzed using Euclidean Distance Matrix Analysis (EDMA) to statistically compare the brains of each non-human ape species to the human sample. Results of analyses show both a pattern of brain morphology that is consistently different between all apes and humans, as well as patterns that differ among species. Further, both the consistent and species-specific patterns include cortical and subcortical features. The pattern that remains consistent across species indicates a morphological reorganization of 1) relationships between cortical and subcortical frontal structures, 2) expansion of the temporal lobe and location of the amygdala, and 3) expansion of the anterior parietal region. Additionally, results demonstrate that, although there is a pattern of morphology that uniquely defines the human brain, there are also patterns that uniquely differentiate human morphology from the morphology of each non-human ape species, indicating that reorganization of neural morphology occurred at the evolutionary divergence of each of these groups. PMID:21056456

Cortical Activation in Response to Pure Taste Stimuli During the Physiological States of Hunger and Satiety

PubMed Central

Haase, Lori; Cerf-Ducastel, Barbara; Murphy, Claire

2009-01-01

This event-related functional magnetic resonance imaging (er-fMRI) study investigated BOLD signal change in response to a series of pure gustatory stimuli that varied in stimulus quality when subjects were hungry and sated with a nutritional preload. Group analyses showed significant differences in activation in the hunger minus satiety condition in response to sucrose, caffeine, saccharin, and citric acid within the thalamus, hippocampus, and parahippocampus. When examining the hunger and satiety conditions, activation varied as a function of stimulus, with the majority of the stimuli exhibiting significantly greater activation in the hunger state within the insula, thalamus, and substantia nigra, in contrast to decreased activation in the satiated state within the parahippocampus, hippocampus, amygdala, and anterior cingulate. Region of interest (ROI) analysis revealed two significant interactions, ROI by physiology and ROI by physiology by stimulus. In the satiety condition, the primary (inferior and superior insulae) and secondary (OFC 11 and OFC 47) taste regions exhibited significantly greater brain activation in response to all stimuli than regions involved in processing eating behavior (hypothalamus), affect (amygdala), and memory (hippocampus, parahippocampus and entorhinal cortex). These same regions demonstrated significantly greater activation within the hunger condition than the satiety condition, with the exception of the superior insula. Furthermore, the patterns of activation differed as a function taste stimulus, with greater activation in response to sucrose than to the other stimuli. These differential patterns of activation suggest that the physiological states of hunger and satiety produce divergent activation in multiple brain areas in response to different pure gustatory stimuli. PMID:19007893

Cortical activation in response to pure taste stimuli during the physiological states of hunger and satiety.

PubMed

Haase, Lori; Cerf-Ducastel, Barbara; Murphy, Claire

2009-02-01

This event-related functional magnetic resonance imaging (er-fMRI) study investigated BOLD signal change in response to a series of pure gustatory stimuli that varied in stimulus quality when subjects were hungry and sated with a nutritional pre-load. Group analyses showed significant differences in activation in the hunger minus satiety condition in response to sucrose, caffeine, saccharin, and citric acid within the thalamus, hippocampus, and parahippocampus. When examining the hunger and satiety conditions, activation varied as a function of stimulus, with the majority of the stimuli exhibiting significantly greater activation in the hunger state within the insula, thalamus, and substantia nigra, in contrast to decreased activation in the satiated state within the parahippocampus, hippocampus, amygdala, and anterior cingulate. Region of interest (ROI) analysis revealed two significant interactions, ROI by physiology and ROI by physiology by stimulus. In the satiety condition, the primary (inferior and superior insulae) and secondary (OFC 11 and OFC 47) taste regions exhibited significantly greater brain activation in response to all stimuli than regions involved in processing eating behavior (hypothalamus), affect (amygdala), and memory (hippocampus, parahippocampus and entorhinal cortex). These same regions demonstrated significantly greater activation within the hunger condition than the satiety condition, with the exception of the superior insula. Furthermore, the patterns of activation differed as a function taste stimulus, with greater activation in response to sucrose than to the other stimuli. These differential patterns of activation suggest that the physiological states of hunger and satiety produce divergent activation in multiple brain areas in response to different pure gustatory stimuli.

Neural substrates of treatment response to cognitive-behavioral therapy in panic disorder with agoraphobia.

PubMed

Lueken, Ulrike; Straube, Benjamin; Konrad, Carsten; Wittchen, Hans-Ulrich; Ströhle, Andreas; Wittmann, André; Pfleiderer, Bettina; Uhlmann, Christina; Arolt, Volker; Jansen, Andreas; Kircher, Tilo

2013-11-01

Although exposure-based cognitive-behavioral therapy (CBT) is an effective treatment option for panic disorder with agoraphobia, the neural substrates of treatment response remain unknown. Evidence suggests that panic disorder with agoraphobia is characterized by dysfunctional safety signal processing. Using fear conditioning as a neurofunctional probe, the authors investigated neural baseline characteristics and neuroplastic changes after CBT that were associated with treatment outcome in patients with panic disorder with agoraphobia. Neural correlates of fear conditioning and extinction were measured using functional MRI before and after a manualized CBT program focusing on behavioral exposure in 49 medication-free patients with a primary diagnosis of panic disorder with agoraphobia. Treatment response was defined as a reduction exceeding 50% in Hamilton Anxiety Rating Scale scores. At baseline, nonresponders exhibited enhanced activation in the right pregenual anterior cingulate cortex, the hippocampus, and the amygdala in response to a safety signal. While this activation pattern partly resolved in nonresponders after CBT, successful treatment was characterized by increased right hippocampal activation when processing stimulus contingencies. Treatment response was associated with an inhibitory functional coupling between the anterior cingulate cortex and the amygdala that did not change over time. This study identified brain activation patterns associated with treatment response in patients with panic disorder with agoraphobia. Altered safety signal processing and anterior cingulate cortex-amygdala coupling may indicate individual differences among these patients that determine the effectiveness of exposure-based CBT and associated neuroplastic changes. Findings point to brain networks by which successful CBT in this patient population is mediated.

Contralateral disconnection of the rat prelimbic cortex and dorsomedial striatum impairs cue-guided behavioral switching

PubMed Central

Baker, Phillip M.

2014-01-01

Switches in reward outcomes or reward-predictive cues are two fundamental ways in which information is used to flexibly shift response patterns. The rat prelimbic cortex and dorsomedial striatum support behavioral flexibility based on a change in outcomes. The present experiments investigated whether these two brain regions are necessary for conditional discrimination performance in which a switch in reward-predictive cues occurs every three to six trials. The GABA agonists baclofen and muscimol infused into the prelimbic cortex significantly impaired performance leading rats to adopt an inappropriate turn strategy. The NMDA receptor antagonist D-AP5 infused into the dorsomedial striatum or prelimbic cortex and dorsomedial striatum contralateral disconnection impaired performance due to a rat failing to switch a response choice for an entire trial block in about two out of 13 test blocks. In an additional study, contralateral disconnection did not affect nonswitch discrimination performance. The results suggest that the prelimbic cortex and dorsomedial striatum are necessary to support cue-guided behavioral switching. The prelimbic cortex may be critical for generating alternative response patterns while the dorsomedial striatum supports the selection of an appropriate response when cue information must be used to flexibly switch response patterns. PMID:25028395

Role of mechanical factors in cortical folding development

NASA Astrophysics Data System (ADS)

Razavi, Mir Jalil; Zhang, Tuo; Li, Xiao; Liu, Tianming; Wang, Xianqiao

2015-09-01

Deciphering mysteries of the structure-function relationship in cortical folding has emerged as the cynosure of recent research on brain. Understanding the mechanism of convolution patterns can provide useful insight into the normal and pathological brain function. However, despite decades of speculation and endeavors the underlying mechanism of the brain folding process remains poorly understood. This paper focuses on the three-dimensional morphological patterns of a developing brain under different tissue specification assumptions via theoretical analyses, computational modeling, and experiment verifications. The living human brain is modeled with a soft structure having outer cortex and inner core to investigate the brain development. Analytical interpretations of differential growth of the brain model provide preliminary insight into the critical growth ratio for instability and crease formation of the developing brain followed by computational modeling as a way to offer clues for brain's postbuckling morphology. Especially, tissue geometry, growth ratio, and material properties of the cortex are explored as the most determinant parameters to control the morphogenesis of a growing brain model. As indicated in results, compressive residual stresses caused by the sufficient growth trigger instability and the brain forms highly convoluted patterns wherein its gyrification degree is specified with the cortex thickness. Morphological patterns of the developing brain predicted from the computational modeling are consistent with our neuroimaging observations, thereby clarifying, in part, the reason of some classical malformation in a developing brain.

1H-MRSI pattern perturbation in a mouse glioma: the effects of acute hyperglycemia and moderate hypothermia.

PubMed

Simões, R V; Delgado-Goñi, T; Lope-Piedrafita, S; Arús, C

2010-01-01

MR spectroscopic Imaging (MRSI), with PRESS localization, is used here to monitor the effects of acute hyperglycemia in the spectral pattern of 11 mice bearing GL261 gliomas at normothermia (36.5-37.5 degrees C) and at hypothermia (28.5-29.5 degrees C). These in vivo studies were complemented by ex vivo high resolution magic angle spinning (HR-MAS) analysis of GL261 tumor samples from 6 animals sacrificed by focused microwave irradiation, and blood glucose measurements in 12 control mice. Apparent glucose levels, monitored by in vivo MRSI in brain tumors during acute hyperglycemia, rose to an average of 1.6-fold during hypothermia (p < 0.05), while no significant changes were detected at normothermia, or in control experiments performed at euglycemia, or in normal/peritumoral brain regions. Ex vivo analysis of glioma-bearing mouse brains at hypothermia revealed higher glucose increases in distinct regions during the acute hyperglycemic challenge (up to 6.6-fold at the tumor center), in agreement with maximal in vivo blood glucose changes (5-fold). Phantom studies on taurine plus glucose containing solutions explained the differences between in vivo and ex vivo measurements. Our results also indicate brain tumor heterogeneity in the four animal tumors investigated in response to a defined metabolic challenge.

How emotional abilities modulate the influence of early life stress on hippocampal functioning.

PubMed

Aust, Sabine; Alkan Härtwig, Elif; Koelsch, Stefan; Heekeren, Hauke R; Heuser, Isabella; Bajbouj, Malek

2014-07-01

Early life stress (ELS) is known to have considerable influence on brain development, mental health and affective functioning. Previous investigations have shown that alexithymia, a prevalent personality trait associated with difficulties experiencing and verbalizing emotions, is particularly related to ELS. The aim of the present study was to investigate how neural correlates of emotional experiences in alexithymia are altered in the presence and absence of ELS. Therefore, 50 healthy individuals with different levels of alexithymia were matched regarding ELS and investigated with respect to neural correlates of audio-visually induced emotional experiences via functional magnetic resonance imaging. The main finding was that ELS modulated hippocampal responses to pleasant (>neutral) stimuli in high-alexithymic individuals, whereas there was no such modulation in low-alexithymic individuals matched for ELS. Behavioral and psychophysiological results followed a similar pattern. When considered independent of ELS, alexithymia was associated with decreased responses in insula (pleasant > neutral) and temporal pole (unpleasant > neutral). Our results show that the influence of ELS on emotional brain responses seems to be modulated by an individual's degree of alexithymia. Potentially, protective and adverse effects of emotional abilities on brain responses to emotional experiences are discussed. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

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.

Modelling Peri-Perceptual Brain Processes in a Deep Learning Spiking Neural Network Architecture.

PubMed

Gholami Doborjeh, Zohreh; Kasabov, Nikola; Gholami Doborjeh, Maryam; Sumich, Alexander

2018-06-11

Familiarity of marketing stimuli may affect consumer behaviour at a peri-perceptual processing level. The current study introduces a method for deep learning of electroencephalogram (EEG) data using a spiking neural network (SNN) approach that reveals the complexity of peri-perceptual processes of familiarity. The method is applied to data from 20 participants viewing familiar and unfamiliar logos. The results support the potential of SNN models as novel tools in the exploration of peri-perceptual mechanisms that respond differentially to familiar and unfamiliar stimuli. Specifically, the activation pattern of the time-locked response identified by the proposed SNN model at approximately 200 milliseconds post-stimulus suggests greater connectivity and more widespread dynamic spatio-temporal patterns for familiar than unfamiliar logos. The proposed SNN approach can be applied to study other peri-perceptual or perceptual brain processes in cognitive and computational neuroscience.

A microfluidic device to study neuronal and motor responses to acute chemical stimuli in zebrafish.

PubMed

Candelier, Raphaël; Murmu, Meena Sriti; Romano, Sebastián Alejo; Jouary, Adrien; Debrégeas, Georges; Sumbre, Germán

2015-07-21

Zebrafish larva is a unique model for whole-brain functional imaging and to study sensory-motor integration in the vertebrate brain. To take full advantage of this system, one needs to design sensory environments that can mimic the complex spatiotemporal stimulus patterns experienced by the animal in natural conditions. We report on a novel open-ended microfluidic device that delivers pulses of chemical stimuli to agarose-restrained larvae with near-millisecond switching rate and unprecedented spatial and concentration accuracy and reproducibility. In combination with two-photon calcium imaging and recordings of tail movements, we found that stimuli of opposite hedonic values induced different circuit activity patterns. Moreover, by precisely controlling the duration of the stimulus (50-500 ms), we found that the probability of generating a gustatory-induced behavior is encoded by the number of neurons activated. This device may open new ways to dissect the neural-circuit principles underlying chemosensory perception.

Changes in EEG alpha power to different disgust elicitors: the specificity of mutilations.

PubMed

Sarlo, Michela; Buodo, Giulia; Poli, Silvia; Palomba, Daniela

2005-07-15

It is unclear in the literature whether the various disgust elicitors are differentially processed by the brain and/or able to elicit distinct psychophysiological response patterns. On the other hand, disgusting stimuli depicting mutilations have been proved to elicit a distinct autonomic response pattern and to demand greater attentional resources, as compared with other unpleasant visual stimuli. In this EEG study, 34 participants viewed 4 film-clips depicting surgery, cockroach invasion, human attack and neutral landscape during EEG recording, and then rated the clips for valence, arousal and the basic emotions. Independent of location, the highest cortical activation was found during the viewing of the surgery scene. Moreover, the above activation was prominent over the right posterior regions.

Inferring consistent functional interaction patterns from natural stimulus FMRI data

PubMed Central

Sun, Jiehuan; Hu, Xintao; Huang, Xiu; Liu, Yang; Li, Kaiming; Li, Xiang; Han, Junwei; Guo, Lei

2014-01-01

There has been increasing interest in how the human brain responds to natural stimulus such as video watching in the neuroimaging field. Along this direction, this paper presents our effort in inferring consistent and reproducible functional interaction patterns under natural stimulus of video watching among known functional brain regions identified by task-based fMRI. Then, we applied and compared four statistical approaches, including Bayesian network modeling with searching algorithms: greedy equivalence search (GES), Peter and Clark (PC) analysis, independent multiple greedy equivalence search (IMaGES), and the commonly used Granger causality analysis (GCA), to infer consistent and reproducible functional interaction patterns among these brain regions. It is interesting that a number of reliable and consistent functional interaction patterns were identified by the GES, PC and IMaGES algorithms in different participating subjects when they watched multiple video shots of the same semantic category. These interaction patterns are meaningful given current neuroscience knowledge and are reasonably reproducible across different brains and video shots. In particular, these consistent functional interaction patterns are supported by structural connections derived from diffusion tensor imaging (DTI) data, suggesting the structural underpinnings of consistent functional interactions. Our work demonstrates that specific consistent patterns of functional interactions among relevant brain regions might reflect the brain's fundamental mechanisms of online processing and comprehension of video messages. PMID:22440644

Estimating repetitive spatiotemporal patterns from resting-state brain activity data.

PubMed

Takeda, Yusuke; Hiroe, Nobuo; Yamashita, Okito; Sato, Masa-Aki

2016-06-01

Repetitive spatiotemporal patterns in spontaneous brain activities have been widely examined in non-human studies. These studies have reported that such patterns reflect past experiences embedded in neural circuits. In human magnetoencephalography (MEG) and electroencephalography (EEG) studies, however, spatiotemporal patterns in resting-state brain activities have not been extensively examined. This is because estimating spatiotemporal patterns from resting-state MEG/EEG data is difficult due to their unknown onsets. Here, we propose a method to estimate repetitive spatiotemporal patterns from resting-state brain activity data, including MEG/EEG. Without the information of onsets, the proposed method can estimate several spatiotemporal patterns, even if they are overlapping. We verified the performance of the method by detailed simulation tests. Furthermore, we examined whether the proposed method could estimate the visual evoked magnetic fields (VEFs) without using stimulus onset information. The proposed method successfully detected the stimulus onsets and estimated the VEFs, implying the applicability of this method to real MEG data. The proposed method was applied to resting-state functional magnetic resonance imaging (fMRI) data and MEG data. The results revealed informative spatiotemporal patterns representing consecutive brain activities that dynamically change with time. Using this method, it is possible to reveal discrete events spontaneously occurring in our brains, such as memory retrieval. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Measuring adult attachment representation in an fMRI environment: concepts and assessment.

PubMed

Buchheim, Anna; George, Carol; Kachele, Horst; Erk, Susanne; Walter, Henrik

2006-01-01

Human attachment is defined as a biologically based behavioral system that influences motivational, cognitive, emotional, and memory processes with respect to intimate relationships (parents, life partner, own children). Recent neurobiological studies in this field have in common that they investigated social relationships by examining fMRI neuroimaging patterns while individuals viewed pictures of their beloved relationship partner versus friends, acquaintances, strangers, or mothers' responses to their young children. The researchers showed that the neural underpinnings of these unique intimate emotional states are linked to functionally specialized areas in the brain. Conceptualizing this work from a behavioral systems-attachment theory perspective, these studies did not directly address the subject's attachment representational system. Traditional attachment theory and research has been built on the analysis of attachment narratives, called 'attachment representation'. The Adult Attachment Projective developed by George and West in 2001 is a set of attachment-based schematic pictures. It is constructed to increasingly activate the participant's attachment system in the course of the task, that is, by the introduction of increasingly stressful attachment scenes concluding with pictures of individuals facing death and potential abuse alone. The attachment patterns are evaluated based on individuals' overall verbal response to the picture set. This paper proposes that the AAP is a fruitful measure to use in an fMRI environment to examine brain activation patterns in adults while they are speaking overtly about attachment stories in a standardized setting.

Selective alignment of brain responses by task demands during semantic processing.

PubMed

Baggio, Giosuè

2012-04-01

The way the brain binds together words to form sentences may depend on whether and how the arising cognitive representation is to be used in behavior. The amplitude of the N400 effect in event-related brain potentials is inversely correlated with the degree of fit of a word's meaning into a semantic representation of the preceding discourse. This study reports a double dissociation in the latency characteristics of the N400 effect depending on task demands. When participants silently read words in a sentence context, without issuing a relevant overt response, greater temporal alignment over recording sites occurs for N400 onsets than peaks. If however a behavior is produced - here pressing a button in a binary probe selection task - exactly the opposite pattern is observed, with stronger alignment of N400 peaks than onsets. The peak amplitude of the N400 effect correlates best with the latency characteristic showing less temporal dispersion. These findings suggest that meaning construction in the brain is subtly affected by task demands, and that there is complex functional integration between semantic combinatorics and control systems handling behavioral goals. Copyright © 2012 Elsevier Ltd. All rights reserved.

Rewiring the Brain: Potential Role of the Premotor Cortex in Motor Control, Learning, and Recovery of Function Following Brain Injury

PubMed Central

Kantak, Shailesh S.; Stinear, James W.; Buch, Ethan R.; Cohen, Leonardo G.

2016-01-01

The brain is a plastic organ with a capability to reorganize in response to behavior and/or injury. Following injury to the motor cortex or emergent corticospinal pathways, recovery of function depends on the capacity of surviving anatomical resources to recover and repair in response to task-specific training. One such area implicated in poststroke reorganization to promote recovery of upper extremity recovery is the premotor cortex (PMC). This study reviews the role of distinct subdivisions of PMC: dorsal (PMd) and ventral (PMv) premotor cortices as critical anatomical and physiological nodes within the neural networks for the control and learning of goal-oriented reach and grasp actions in healthy individuals and individuals with stroke. Based on evidence emerging from studies of intrinsic and extrinsic connectivity, transcranial magnetic stimulation, functional neuroimaging, and experimental studies in animals and humans, the authors propose 2 distinct patterns of reorganization that differentially engage ipsilesional and contralesional PMC. Research directions that may offer further insights into the role of PMC in motor control, learning, and poststroke recovery are also proposed. This research may facilitate neuroplasticity for maximal recovery of function following brain injury. PMID:21926382

Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain.

PubMed

Sawicki, C M; McKim, D B; Wohleb, E S; Jarrett, B L; Reader, B F; Norden, D M; Godbout, J P; Sheridan, J F

2015-08-27

Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b(+) cells (microglia/macrophages) and enriched GLAST-1(+)/CD11b(-) cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain region-dependent manner. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Social defeat promotes a reactive endothelium in a brain region-dependent manner with increased expression of key adhesion molecules, selectins and chemokines associated with the recruitment of myeloid cells to the brain

PubMed Central

Sawicki, Caroline M.; McKim, Daniel B.; Wohleb, Eric S.; Jarrett, Brant L.; Reader, Brenda F.; Norden, Diana M.; Godbout, Jonathan P.; Sheridan, John F.

2014-01-01

Repeated social defeat (RSD) in mice causes myeloid cell trafficking to the brain that contributes to the development of prolonged anxiety-like behavior. Myeloid cell recruitment following RSD occurs in regions where neuronal and microglia activation is observed. Thus, we hypothesized that crosstalk between neurons, microglia, and endothelial cells contributes to brain-myeloid cell trafficking via chemokine signaling and vascular adhesion molecules. Here we show that social defeat caused an exposure- and brain region-dependent increase in several key adhesion molecules and chemokines involved in the recruitment of myeloid cells. For example, RSD induced distinct patterns of adhesion molecule expression that may explain brain region-dependent myeloid cell trafficking. VCAM-1 and ICAM-1 mRNA expression were increased in an exposure-dependent manner. Furthermore, RSD-induced VCAM-1 and ICAM-1 protein expression were localized to the vasculature of brain regions implicated in fear and anxiety responses, which spatially corresponded to previously reported patterns of myeloid cell trafficking. Next, mRNA expression of additional adhesion molecules (E- and P-selectin, PECAM-1) and chemokines (CXCL1, CXCL2, CXCL12, CCL2) were determined in the brain. Social defeat induced an exposure-dependent increase in mRNA levels of E-selectin, CXCL1, and CXCL2 that increased with additional days of social defeat. While CXCL12 was unaffected by RSD, CCL2 expression was increased by six days of social defeat. Last, comparison between enriched CD11b+ cells (microglia/macrophages) and enriched GLAST-1+/CD11b− cells (astrocytes) revealed RSD increased mRNA expression of IL-1β, CCL2, and CXCL2 in microglia/macrophages but not in astrocytes. Collectively, these data indicate that key mediators of leukocyte recruitment were increased in the brain vasculature following RSD in an exposure- and brain-region dependent manner. PMID:25445193

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.

The role of sensorimotor learning in the perception of letter-like forms: tracking the causes of neural specialization for letters.

PubMed

James, Karin H; Atwood, Thea P

2009-02-01

Functional specialization in the brain is considered a hallmark of efficient processing. It is therefore not surprising that there are brain areas specialized for processing letters. To better understand the causes of functional specialization for letters, we explore the emergence of this pattern of response in the ventral processing stream through a training paradigm. Previously, we hypothesized that the specialized response pattern seen during letter perception may be due in part to our experience in writing letters. The work presented here investigates whether or not this aspect of letter processing-the integration of sensorimotor systems through writing-leads to functional specialization in the visual system. To test this idea, we investigated whether or not different types of experiences with letter-like stimuli ("pseudoletters") led to functional specialization similar to that which exists for letters. Neural activation patterns were measured using functional magnetic resonance imaging (fMRI) before and after three different types of training sessions. Participants were trained to recognize pseudoletters by writing, typing, or purely visual practice. Results suggested that only after writing practice did neural activation patterns to pseudoletters resemble patterns seen for letters. That is, neural activation in the left fusiform and dorsal precentral gyrus was greater when participants viewed pseudoletters than other, similar stimuli but only after writing experience. Neural activation also increased after typing practice in the right fusiform and left precentral gyrus, suggesting that in some areas, any motor experience may change visual processing. The results of this experiment suggest an intimate interaction among perceptual and motor systems during pseudoletter perception that may be extended to everyday letter perception.

Resting-state brain activity in the motor cortex reflects task-induced activity: A multi-voxel pattern analysis.

PubMed

Kusano, Toshiki; Kurashige, Hiroki; Nambu, Isao; Moriguchi, Yoshiya; Hanakawa, Takashi; Wada, Yasuhiro; Osu, Rieko

2015-08-01

It has been suggested that resting-state brain activity reflects task-induced brain activity patterns. In this study, we examined whether neural representations of specific movements can be observed in the resting-state brain activity patterns of motor areas. First, we defined two regions of interest (ROIs) to examine brain activity associated with two different behavioral tasks. Using multi-voxel pattern analysis with regularized logistic regression, we designed a decoder to detect voxel-level neural representations corresponding to the tasks in each ROI. Next, we applied the decoder to resting-state brain activity. We found that the decoder discriminated resting-state neural activity with accuracy comparable to that associated with task-induced neural activity. The distribution of learned weighted parameters for each ROI was similar for resting-state and task-induced activities. Large weighted parameters were mainly located on conjunctive areas. Moreover, the accuracy of detection was higher than that for a decoder whose weights were randomly shuffled, indicating that the resting-state brain activity includes multi-voxel patterns similar to the neural representation for the tasks. Therefore, these results suggest that the neural representation of resting-state brain activity is more finely organized and more complex than conventionally considered.

Visual brain activity patterns classification with simultaneous EEG-fMRI: A multimodal approach.

PubMed

Ahmad, Rana Fayyaz; Malik, Aamir Saeed; Kamel, Nidal; Reza, Faruque; Amin, Hafeez Ullah; Hussain, Muhammad

2017-01-01

Classification of the visual information from the brain activity data is a challenging task. Many studies reported in the literature are based on the brain activity patterns using either fMRI or EEG/MEG only. EEG and fMRI considered as two complementary neuroimaging modalities in terms of their temporal and spatial resolution to map the brain activity. For getting a high spatial and temporal resolution of the brain at the same time, simultaneous EEG-fMRI seems to be fruitful. In this article, we propose a new method based on simultaneous EEG-fMRI data and machine learning approach to classify the visual brain activity patterns. We acquired EEG-fMRI data simultaneously on the ten healthy human participants by showing them visual stimuli. Data fusion approach is used to merge EEG and fMRI data. Machine learning classifier is used for the classification purposes. Results showed that superior classification performance has been achieved with simultaneous EEG-fMRI data as compared to the EEG and fMRI data standalone. This shows that multimodal approach improved the classification accuracy results as compared with other approaches reported in the literature. The proposed simultaneous EEG-fMRI approach for classifying the brain activity patterns can be helpful to predict or fully decode the brain activity patterns.

A Statistically Representative Atlas for Mapping Neuronal Circuits in the Drosophila Adult Brain

PubMed Central

Arganda-Carreras, Ignacio; Manoliu, Tudor; Mazuras, Nicolas; Schulze, Florian; Iglesias, Juan E.; Bühler, Katja; Jenett, Arnim; Rouyer, François; Andrey, Philippe

2018-01-01

Imaging the expression patterns of reporter constructs is a powerful tool to dissect the neuronal circuits of perception and behavior in the adult brain of Drosophila, one of the major models for studying brain functions. To date, several Drosophila brain templates and digital atlases have been built to automatically analyze and compare collections of expression pattern images. However, there has been no systematic comparison of performances between alternative atlasing strategies and registration algorithms. Here, we objectively evaluated the performance of different strategies for building adult Drosophila brain templates and atlases. In addition, we used state-of-the-art registration algorithms to generate a new group-wise inter-sex atlas. Our results highlight the benefit of statistical atlases over individual ones and show that the newly proposed inter-sex atlas outperformed existing solutions for automated registration and annotation of expression patterns. Over 3,000 images from the Janelia Farm FlyLight collection were registered using the proposed strategy. These registered expression patterns can be searched and compared with a new version of the BrainBaseWeb system and BrainGazer software. We illustrate the validity of our methodology and brain atlas with registration-based predictions of expression patterns in a subset of clock neurons. The described registration framework should benefit to brain studies in Drosophila and other insect species. PMID:29628885

The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults

PubMed Central

Cortese, Bernadette M.; Uhde, Thomas W.; Brady, Kathleen T.; McClernon, F. Joseph; Yang, Qing X.; Collins, Heather R.; LeMatty, Todd; Hartwell, Karen J.

2015-01-01

Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor + picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multi-sensory, but not unisensory cues, was significantly related to participants’ level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. PMID:26475784

The fMRI BOLD response to unisensory and multisensory smoking cues in nicotine-dependent adults.

PubMed

Cortese, Bernadette M; Uhde, Thomas W; Brady, Kathleen T; McClernon, F Joseph; Yang, Qing X; Collins, Heather R; LeMatty, Todd; Hartwell, Karen J

2015-12-30

Given that the vast majority of functional magnetic resonance imaging (fMRI) studies of drug cue reactivity use unisensory visual cues, but that multisensory cues may elicit greater craving-related brain responses, the current study sought to compare the fMRI BOLD response to unisensory visual and multisensory, visual plus odor, smoking cues in 17 nicotine-dependent adult cigarette smokers. Brain activation to smoking-related, compared to neutral, pictures was assessed under cigarette smoke and odorless odor conditions. While smoking pictures elicited a pattern of activation consistent with the addiction literature, the multisensory (odor+picture) smoking cues elicited significantly greater and more widespread activation in mainly frontal and temporal regions. BOLD signal elicited by the multisensory, but not unisensory cues, was significantly related to participants' level of control over craving as well. Results demonstrated that the co-presentation of cigarette smoke odor with smoking-related visual cues, compared to the visual cues alone, elicited greater levels of craving-related brain activation in key regions implicated in reward. These preliminary findings support future research aimed at a better understanding of multisensory integration of drug cues and craving. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Changes in Regional Brain Homogeneity Induced by Electro-Acupuncture Stimulation at the Baihui Acupoint in Healthy Subjects: A Functional Magnetic Resonance Imaging Study.

PubMed

Deng, Demao; Duan, Gaoxiong; Liao, Hai; Liu, Yanfei; Wang, Geliang; Liu, Huimei; Tang, Lijun; Pang, Yong; Tao, Jien; He, Xin; Yuan, Wenzhao; Liu, Peng

2016-10-01

According to the Traditional Chinese Medicine theory of acupuncture, Baihui (GV20) is applied to treat neurological and psychiatric disorders. However, the relationships between neural responses and GV20 remain unknown. Thus, the main aim of this study was to examine the brain responses induced by electro-acupuncture stimulation (EAS) at GV20. Functional magnetic resonance imaging (fMRI) was performed in 33 healthy subjects. Based on the non-repeated event-related (NRER) paradigm, group differences were examined between GV20 and a sham acupoint using the regional homogeneity (ReHo) method. Compared with the sham acupoint, EAS at GV20 induced increased ReHo in regions including the orbital frontal cortex (OFC), middle cingulate cortex (MCC), precentral cortex, and precuneus (preCUN). Decreased ReHo was found in the anterior cingulate cortex (ACC), supplementary motor area (SMA), thalamus, putamen, and cerebellum. The current findings provide preliminary neuroimaging evidence to indicate that EAS at GV20 could induce a specific pattern of neural responses by analysis of ReHo of brain activity. These findings might improve the understanding of mechanisms of acupuncture stimulation at GV20.

Virtual Milgram: Empathic Concern or Personal Distress? Evidence from Functional MRI and Dispositional Measures

PubMed Central

Cheetham, Marcus; Pedroni, Andreas F.; Antley, Angus; Slater, Mel; Jäncke, Lutz

2009-01-01

One motive for behaving as the agent of another's aggression appears to be anchored in as yet unelucidated mechanisms of obedience to authority. In a recent partial replication of Milgram's obedience paradigm within an immersive virtual environment, participants administered pain to a female virtual human and observed her suffering. Whether the participants’ response to the latter was more akin to other-oriented empathic concern for her well-being or to a self-oriented aversive state of personal distress in response to her distress is unclear. Using the stimuli from that study, this event-related fMRI-based study analysed brain activity during observation of the victim in pain versus not in pain. This contrast revealed activation in pre-defined brain areas known to be involved in affective processing but not in those commonly associated with affect sharing (e.g., ACC and insula). We then examined whether different dimensions of dispositional empathy predict activity within the same pre-defined brain regions: While personal distress and fantasy (i.e., tendency to transpose oneself into fictional situations and characters) predicted brain activity, empathic concern and perspective taking predicted no change in neuronal response associated with pain observation. These exploratory findings suggest that there is a distinct pattern of brain activity associated with observing the pain-related behaviour of the victim within the context of this social dilemma, that this observation evoked a self-oriented aversive state of personal distress, and that the objective “reality” of pain is of secondary importance for this response. These findings provide a starting point for experimentally more rigorous investigation of obedience. PMID:19876407

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

Inflammatory Disequilibrium in Stroke

PubMed Central

Petrovic-Djergovic, Danica; Goonewardena, Sascha N.; Pinsky, David J.

2016-01-01

Over the past several decades, there have been substantial advances in our knowledge of the pathophysiology of stroke. Understanding the benefits of timely reperfusion has led to the development of thrombolytic therapy as the cornerstone of current management of ischemic stroke, but there remains much to be learned about mechanisms of neuronal ischemic and reperfusion injury and associated inflammation. For ischemic stroke, novel therapeutic targets have continued to remain elusive. When considering modern molecular biologic techniques, advanced translational stroke models, and clinical studies, a consistent pattern emerges, implicating perturbation of the immune equilibrium by stroke in both central nervous system injury and repair responses. Stroke triggers activation of the neuroimmune axis, comprised of multiple cellular constituents of the immune system resident within the parenchyma of the brain, leptomeninges, and vascular beds, as well as through secretion of biological response modifiers and recruitment of immune effector cells. This neuroimmune activation can directly impact the initiation, propagation, and resolution phases of ischemic brain injury. In order to leverage a potential opportunity to modulate local and systemic immune responses to favorably affect the stroke disease curve, it is necessary to expand our mechanistic understanding of the neuroimmune axis in ischemic stroke. This review explores the frontiers of current knowledge of innate and adaptive immune responses in the brain and how these responses together shape the course of ischemic stroke. PMID:27340273

Efficiency of weak brain connections support general cognitive functioning.

PubMed

Santarnecchi, Emiliano; Galli, Giulia; Polizzotto, Nicola Riccardo; Rossi, Alessandro; Rossi, Simone

2014-09-01

Brain network topology provides valuable information on healthy and pathological brain functioning. Novel approaches for brain network analysis have shown an association between topological properties and cognitive functioning. Under the assumption that "stronger is better", the exploration of brain properties has generally focused on the connectivity patterns of the most strongly correlated regions, whereas the role of weaker brain connections has remained obscure for years. Here, we assessed whether the different strength of connections between brain regions may explain individual differences in intelligence. We analyzed-functional connectivity at rest in ninety-eight healthy individuals of different age, and correlated several connectivity measures with full scale, verbal, and performance Intelligent Quotients (IQs). Our results showed that the variance in IQ levels was mostly explained by the distributed communication efficiency of brain networks built using moderately weak, long-distance connections, with only a smaller contribution of stronger connections. The variability in individual IQs was associated with the global efficiency of a pool of regions in the prefrontal lobes, hippocampus, temporal pole, and postcentral gyrus. These findings challenge the traditional view of a prominent role of strong functional brain connections in brain topology, and highlight the importance of both strong and weak connections in determining the functional architecture responsible for human intelligence variability. Copyright © 2014 Wiley Periodicals, Inc.

Brain network dysfunction in youth with obsessive-compulsive disorder induced by simple uni-manual behavior: The role of the dorsal anterior cingulate cortex

PubMed Central

Friedman, Amy L.; Burgess, Ashley; Ramaseshan, Karthik; Easter, Phil; Khatib, Dalal; Chowdury, Asadur; Arnold, Paul D.; Hanna, Gregory L.; Rosenberg, David R.; Diwadkar, Vaibhav A.

2017-01-01

In an effort to elucidate differences in functioning brain networks between youth with obsessive-compulsive disorder and controls, we used fMRI signals to analyze brain network interactions of the dorsal anterior cingulate cortex (dACC) during visually coordinated motor responses. Subjects made a uni-manual response to briefly presented probes, at periodic (allowing participants to maintain a “motor set”) or random intervals (demanding reactive responses). Network interactions were assessed using psycho-physiological interaction (PPI), a basic model of functional connectivity evaluating modulatory effects of the dACC in the context of each task condition. Across conditions, OCD were characterized by hyper-modulation by the dACC, with loci alternatively observed as both condition-general and condition-specific. Thus, dynamically driven task demands during simple uni-manual motor control induce compensatory network interactions in cortical-thalamic regions in OCD. These findings support previous research in OCD showing compensatory network interactions during complex memory tasks, but establish that these network effects are observed during basic sensorimotor processing. Thus, these patterns of network dysfunction may in fact be independent of the complexity of tasks used to induce brain network activity. Hypothesis-driven approaches coupled with sophisticated network analyses are a highly valuable approach in using fMRI to uncover mechanisms in disorders like OCD. PMID:27992792

Developmental pattern of diacylglycerol lipase-α (DAGLα) immunoreactivity in brain regions important for song learning and control in the zebra finch (Taeniopygia guttata).

PubMed

Soderstrom, Ken; Wilson, Ashley R

2013-11-01

Zebra finch song is a learned behavior dependent upon successful progress through a sensitive period of late-postnatal development. This learning is associated with maturation of distinct brain nuclei and the fiber tract interconnections between them. We have previously found remarkably distinct and dense CB1 cannabinoid receptor expression within many of these song control brain regions, implying a normal role for endocannabinoid signaling in vocal learning. Activation of CB1 receptors via daily treatments with exogenous agonist during sensorimotor stages of song learning (but not in adulthood) results in persistent alteration of song patterns. Now we are working to understand physiological changes responsible for this cannabinoid-altered vocal learning. We have found that song-altering developmental treatments are associated with changes in expression of endocannabinoid signaling elements, including CB1 receptors and the principal CNS endogenous agonist, 2-AG. Within CNS, 2-AG is produced largely through activity of the α isoform of the enzyme diacylglycerol lipase (DAGLα). To better appreciate the role of 2-AG production in normal vocal development we have determined the spatial distribution of DAGLα expression within zebra finch CNS during vocal development. Early during vocal development at 25 days, DAGLα staining is typically light and of fibroid processes. Staining peaks late in the sensorimotor stage of song learning at 75 days and is characterized by fiber, neuropil and some staining of both small and large cell somata. Results provide insight to the normal role for endocannabinoid signaling in the maturation of brain regions responsible for song learning and vocal-motor output, and suggest mechanisms by which exogenous cannabinoid exposure alters acquisition of this form of vocal communication. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of Different Movement Speed Modes on Human Action Observation: An EEG Study.

PubMed

Luo, Tian-Jian; Lv, Jitu; Chao, Fei; Zhou, Changle

2018-01-01

Action observation (AO) generates event-related desynchronization (ERD) suppressions in the human brain by activating partial regions of the human mirror neuron system (hMNS). The activation of the hMNS response to AO remains controversial for several reasons. Therefore, this study investigated the activation of the hMNS response to a speed factor of AO by controlling the movement speed modes of a humanoid robot's arm movements. Since hMNS activation is reflected by ERD suppressions, electroencephalography (EEG) with BCI analysis methods for ERD suppressions were used as the recording and analysis modalities. Six healthy individuals were asked to participate in experiments comprising five different conditions. Four incremental-speed AO tasks and a motor imagery (MI) task involving imaging of the same movement were presented to the individuals. Occipital and sensorimotor regions were selected for BCI analyses. The experimental results showed that hMNS activation was higher in the occipital region but more robust in the sensorimotor region. Since the attended information impacts the activations of the hMNS during AO, the pattern of hMNS activations first rises and subsequently falls to a stable level during incremental-speed modes of AO. The discipline curves suggested that a moderate speed within a decent inter-stimulus interval (ISI) range produced the highest hMNS activations. Since a brain computer/machine interface (BCI) builds a path-way between human and computer/mahcine, the discipline curves will help to construct BCIs made by patterns of action observation (AO-BCI). Furthermore, a new method for constructing non-invasive brain machine brain interfaces (BMBIs) with moderate AO-BCI and motor imagery BCI (MI-BCI) was inspired by this paper.

Inflammation in Alzheimer's disease: amyloid-beta oligomers trigger innate immunity defence via pattern recognition receptors.

PubMed

Salminen, Antero; Ojala, Johanna; Kauppinen, Anu; Kaarniranta, Kai; Suuronen, Tiina

2009-02-01

The inflammatory process has a fundamental role in the pathogenesis of Alzheimer's disease (AD). Recent studies indicate that inflammation is not merely a bystander in neurodegeneration but a powerful pathogenetic force in the disease process. Increased production of amyloid-beta peptide species can activate the innate immunity system via pattern recognition receptors (PRRs) and evoke Alzheimer's pathology. We will focus on the role of innate immunity system of brain in the initiation and the propagation of inflammatory process in AD. We examine here in detail the significance of amyloid-beta oligomers and fibrils as danger-associated molecular patterns (DAMPs) in the activation of a wide array of PRRs in glial cells and neurons, such as Toll-like, NOD-like, formyl peptide, RAGE and scavenger receptors along with complement and pentraxin systems. We also characterize the signaling pathways triggered by different PRRs in evoking inflammatory responses. In addition, we will discuss whether AD pathology could be the outcome of chronic activation of the innate immunity defence in the brain of AD patients.

Addition of deep brain stimulation signal to a local field potential driven Izhikevich model masks the pathological firing pattern of an STN neuron.

PubMed

Michmizos, Kostis P; Nikita, Konstantina S

2011-01-01

The crucial engagement of the subthalamic nucleus (STN) with the neurosurgical procedure of deep brain stimulation (DBS) that alleviates medically intractable Parkinsonian tremor augments the need to refine our current understanding of STN. To enhance the efficacy of DBS as a result of precise targeting, STN boundaries are accurately mapped using extracellular microelectrode recordings (MERs). We utilized the intranuclear MER to acquire the local field potential (LFP) and drive an Izhikevich model of an STN neuron. Using the model as the test bed for clinically acquired data, we demonstrated that stimulation of the STN neuron produces excitatory responses that tonically increase its average firing rate and alter the pattern of its neuronal activity. We also found that the spiking rhythm increases linearly with the increase of amplitude, frequency, and duration of the DBS pulse, inside the clinical range. Our results are in agreement with the current hypothesis that DBS increases the firing rate of STN and masks its pathological bursting firing pattern.

Identifying ADHD children using hemodynamic responses during a working memory task measured by functional near-infrared spectroscopy.

PubMed

Gu, Yue; Miao, Shuo; Han, Junxia; Liang, Zhenhu; Ouyang, Gaoxiang; Yang, Jian; Li, Xiaoli

2018-06-01

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting children and adults. Previous studies found that functional near-infrared spectroscopy (fNIRS) can reveal significant group differences in several brain regions between ADHD children and healthy controls during working memory tasks. This study aimed to use fNIRS activation patterns to identify ADHD children from healthy controls. FNIRS signals from 25 ADHD children and 25 healthy controls performing the n-back task were recorded; then, multivariate pattern analysis was used to discriminate ADHD individuals from healthy controls, and classification performance was evaluated for significance by the permutation test. The results showed that 86.0% ([Formula: see text]) of participants can be correctly classified in leave-one-out cross-validation. The most discriminative brain regions included the bilateral dorsolateral prefrontal cortex, inferior medial prefrontal cortex, right posterior prefrontal cortex, and right temporal cortex. This study demonstrated that, in a small sample, multivariate pattern analysis can effectively identify ADHD children from healthy controls based on fNIRS signals, which argues for the potential utility of fNIRS in future assessments.

Differential brain responses to cries of infants with autistic disorder and typical development: an fMRI study.

PubMed

Venuti, Paola; Caria, Andrea; Esposito, Gianluca; De Pisapia, Nicola; Bornstein, Marc H; de Falco, Simona

2012-01-01

This study used fMRI to measure brain activity during adult processing of cries of infants with autistic disorder (AD) compared to cries of typically developing (TD) infants. Using whole brain analysis, we found that cries of infants with AD compared to those of TD infants elicited enhanced activity in brain regions associated with verbal and prosodic processing, perhaps because altered acoustic patterns of AD cries render them especially difficult to interpret, and increased activity in brain regions associated with emotional processing, indicating that AD cries also elicit more negative feelings and may be perceived as more aversive and/or arousing. Perceived distress engendered by AD cries related to increased activation in brain regions associated with emotional processing. This study supports the hypothesis that cry is an early and meaningful anomaly displayed by children with AD. It could be that cries associated with AD alter parent-child interactions much earlier than the time that reliable AD diagnosis normally occurs. Copyright © 2012 Elsevier Ltd. All rights reserved.

Developing a Performance Brain Training™ approach for baseball: a process analysis with descriptive data.

PubMed

Sherlin, Leslie H; Larson, Noel C; Sherlin, Rebecca M

2013-03-01

Neurofeedback may be useful for improving sports performance but few studies have examined this potential. Here we present data of five development players from a major league baseball team. The aims were to evaluate the feasibility of conducting sessions within a professional organization, assess changes in quantitative electroencephalograph (QEEG), NeuroPerformance Profile™, and report qualitative self-report data before and after brain training. The EEG was recorded with 19 electrodes for 20 min of baseline conditions and approximately 21 min of a continuous performance test. The fast Fourier transform analysis provided average cross-spectral matrices for bands delta (1-3.5 Hz), theta (4-7.5 Hz), alpha (8-12 Hz), low beta (13-16 Hz), beta 1 (13-21 Hz), beta 2 (22-32 Hz), and gamma (32-45 Hz) from the pre and post intervention evaluations in the baseline condition of eyes open. The continuous performance test metrics included the errors of omission, errors of commission, response time and response time variability. The 9 scales of the NeuroPerformance Profile™ were examined. The QEEG data, CPT data and NeuroPerformance Profile™ data were all compared between the pre and post 15 sessions of brain training using a within subject paired t test design corrected for multiple comparisons using false discovery rate method. Following brain training, comparative QEEG, CPT and NeuroPerformance Profile™ analyses illustrated significant differences. The QEEG findings of all participants illustrated significant changes within the training parameters but also across other frequency bands and electrode sites. Overall, the positive findings in both objective and subjective measures suggest further inquiry into the utility of brain training for performance enhancement with the specific application of sport is warranted. Particularly QEEG and CPT gains were noted in the areas that correspond to client self-report data demonstrating improvement in attention, decreased intrusive thought patterns and improvements in sleep patterns.

Functional Connectivity During Exposure to Favorite-Food, Stress, and Neutral-Relaxing Imagery Differs Between Smokers and Nonsmokers.

PubMed

Garrison, Kathleen A; Sinha, Rajita; Lacadie, Cheryl M; Scheinost, Dustin; Jastreboff, Ania M; Constable, R Todd; Potenza, Marc N

2016-09-01

Tobacco-use disorder is a complex condition involving multiple brain networks and presenting with multiple behavioral correlates including changes in diet and stress. In a previous functional magnetic resonance imaging (fMRI) study of neural responses to favorite-food, stress, and neutral-relaxing imagery, smokers versus nonsmokers demonstrated blunted corticostriatal-limbic responses to favorite-food cues. Based on other recent reports of alterations in functional brain networks in smokers, the current study examined functional connectivity during exposure to favorite-food, stress, and neutral-relaxing imagery in smokers and nonsmokers, using the same dataset. The intrinsic connectivity distribution was measured to identify brain regions that differed in degree of functional connectivity between groups during each imagery condition. Resulting clusters were evaluated for seed-to-voxel connectivity to identify the specific connections that differed between groups during each imagery condition. During exposure to favorite-food imagery, smokers versus nonsmokers showed lower connectivity in the supramarginal gyrus, and differences in connectivity between the supramarginal gyrus and the corticostriatal-limbic system. During exposure to neutral-relaxing imagery, smokers versus nonsmokers showed greater connectivity in the precuneus, and greater connectivity between the precuneus and the posterior insula and rolandic operculum. During exposure to stress imagery, smokers versus nonsmokers showed lower connectivity in the cerebellum. These findings provide data-driven insights into smoking-related alterations in brain functional connectivity patterns related to appetitive, relaxing, and stressful states. This study uses a data-driven approach to demonstrate that smokers and nonsmokers show differential patterns of functional connectivity during guided imagery related to personalized favorite-food, stress, and neutral-relaxing cues, in brain regions implicated in attention, reward-related, emotional, and motivational processes. For smokers, these differences in connectivity may impact appetite, stress, and relaxation, and may interfere with smoking cessation. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Functional Connectivity During Exposure to Favorite-Food, Stress, and Neutral-Relaxing Imagery Differs Between Smokers and Nonsmokers

PubMed Central

Sinha, Rajita; Lacadie, Cheryl M.; Scheinost, Dustin; Jastreboff, Ania M.; Constable, R. Todd; Potenza, Marc N.

2016-01-01

Introduction: Tobacco-use disorder is a complex condition involving multiple brain networks and presenting with multiple behavioral correlates including changes in diet and stress. In a previous functional magnetic resonance imaging (fMRI) study of neural responses to favorite-food, stress, and neutral-relaxing imagery, smokers versus nonsmokers demonstrated blunted corticostriatal-limbic responses to favorite-food cues. Based on other recent reports of alterations in functional brain networks in smokers, the current study examined functional connectivity during exposure to favorite-food, stress, and neutral-relaxing imagery in smokers and nonsmokers, using the same dataset. Methods: The intrinsic connectivity distribution was measured to identify brain regions that differed in degree of functional connectivity between groups during each imagery condition. Resulting clusters were evaluated for seed-to-voxel connectivity to identify the specific connections that differed between groups during each imagery condition. Results: During exposure to favorite-food imagery, smokers versus nonsmokers showed lower connectivity in the supramarginal gyrus, and differences in connectivity between the supramarginal gyrus and the corticostriatal-limbic system. During exposure to neutral-relaxing imagery, smokers versus nonsmokers showed greater connectivity in the precuneus, and greater connectivity between the precuneus and the posterior insula and rolandic operculum. During exposure to stress imagery, smokers versus nonsmokers showed lower connectivity in the cerebellum. Conclusions: These findings provide data-driven insights into smoking-related alterations in brain functional connectivity patterns related to appetitive, relaxing, and stressful states. Implications: This study uses a data-driven approach to demonstrate that smokers and nonsmokers show differential patterns of functional connectivity during guided imagery related to personalized favorite-food, stress, and neutral-relaxing cues, in brain regions implicated in attention, reward-related, emotional, and motivational processes. For smokers, these differences in connectivity may impact appetite, stress, and relaxation, and may interfere with smoking cessation. PMID:26995796

Harmonic Brain Modes: A Unifying Framework for Linking Space and Time in Brain Dynamics.

PubMed

Atasoy, Selen; Deco, Gustavo; Kringelbach, Morten L; Pearson, Joel

2018-06-01

A fundamental characteristic of spontaneous brain activity is coherent oscillations covering a wide range of frequencies. Interestingly, these temporal oscillations are highly correlated among spatially distributed cortical areas forming structured correlation patterns known as the resting state networks, although the brain is never truly at "rest." Here, we introduce the concept of harmonic brain modes-fundamental building blocks of complex spatiotemporal patterns of neural activity. We define these elementary harmonic brain modes as harmonic modes of structural connectivity; that is, connectome harmonics, yielding fully synchronous neural activity patterns with different frequency oscillations emerging on and constrained by the particular structure of the brain. Hence, this particular definition implicitly links the hitherto poorly understood dimensions of space and time in brain dynamics and its underlying anatomy. Further we show how harmonic brain modes can explain the relationship between neurophysiological, temporal, and network-level changes in the brain across different mental states ( wakefulness, sleep, anesthesia, psychedelic). Notably, when decoded as activation of connectome harmonics, spatial and temporal characteristics of neural activity naturally emerge from the interplay between excitation and inhibition and this critical relation fits the spatial, temporal, and neurophysiological changes associated with different mental states. Thus, the introduced framework of harmonic brain modes not only establishes a relation between the spatial structure of correlation patterns and temporal oscillations (linking space and time in brain dynamics), but also enables a new dimension of tools for understanding fundamental principles underlying brain dynamics in different states of consciousness.

Electrophysiology quantitative electroencephalography/low resolution brain electromagnetic tomography functional brain imaging (QEEG LORETA): Case report: Subjective idiopathic tinnitus - predominantly central type severe disabling tinnitus.

PubMed

Shulman, Abraham; Goldstein, Barbara

2014-01-01

The clinical significance of QEEG LORETA data analysis performed sequentially within 6 months is presented in a case report of a predominantly central type severe disabling subjective idiopathic tinnitus (SIT) before and following treatment. The QEEG LORETA data is reported as Z-scores of z = ± 2.54, p < 0.013. The focus is on demonstration of patterns of brain wave oscillations reflecting multiple brain functions in multiple ROIs in the presence of the tinnitus signal (SIT). The patterns of brain activity both high, middle and low frequencies are hypothesized to reflect connectivities within and between multiple neuronal networks in brain. The Loreta source localization non auditory ROI Images at the maximal abnormality in the very narrow band frequency spectra (24.21 Hz), showed the mathematically most probable underlying sources of the scalp recorded data to be greatest in the mid-cingulate, bilateral precuneus, cingulate and the bilateral caudate nucleus. Clinical correlation of the data with the history and course of the SIT is considered an objective demonstration of the affect, behavioral, and emotional component of the SIT. The correlation of the caudate activity, SIT as the traumatic event with the clinical course of PTSD, and the clinical diagnosis of PTSD is discussed. The clinical translation for patient care is highlighted in a SIT patient with multiple comorbidities by translation of QEEG/LORETA electrophysiologic data, as an adjunct to: provide an objectivity of patterns of brain wave activity in multiple regions of interest (ROIs) reflecting multiple brain functions, in response to and in the presence of the tinnitus signal, recorded from the scalp and analyzed with the metrics of absolute power, relative power, asymmetry, and coherence, for the subjective tinnitus complaint (SIT); 2) provide an increase in the accuracy of the tinnitus diagnosis; 3) assess/monitor treatment efficacy; 4) provide a rationale for selection of a combined tinnitus targeted therapy of behavioral, pharmacologic, sound therapy modalities of treatment attempting tinnitus relief; 5) provide insight into the medical significance of the SIT; 6) attempt discriminant function analysis for identification of a particular diagnostic clinical category of CNS neuropsychiatric disease; and 7) attempt to translate what is known of the neuroscience of sensation, brain function, QEEG/LORETA source localization, for the etiology and prognosis of the individual SIT patient.

Probabilistic atlases for face and biological motion perception: an analysis of their reliability and overlap.

PubMed

Engell, Andrew D; McCarthy, Gregory

2013-07-01

Neuroimaging research has identified several category-selective regions in visual cortex that respond most strongly when viewing an exemplar image from a preferred category, such as faces. Recent studies, however, have suggested a more complex pattern of activation that has been heretofore unrecognized, e.g., the presence of additional patches of activation to faces beyond the well-studied fusiform face area, and the activation of ostensible face selective regions by animate motion of non-biological forms. Here, we characterize the spatial pattern of brain activity evoked by viewing faces or biological motion in large fMRI samples (N>120). We create probabilistic atlases for both face and biological motion activation, and directly compare their spatial patterns of activation. Our findings support the suggestion that the fusiform face area is composed of at least two separable foci of activation. The face-evoked response in the fusiform and nearby ventral temporal cortex has good reliability across runs; however, we found surprisingly high variability in lateral brain regions by faces, and for all brain regions by biological motion, which had an overall much lower effect size. We found that faces and biological motion evoke substantially overlapping activation distributions in both ventral and lateral occipitotemporal cortices. The peaks of activation for these different categories within these overlapping regions were close but distinct. Copyright © 2013 Elsevier Inc. All rights reserved.

The problem with value

PubMed Central

O’Doherty, John P.

2015-01-01

Neural correlates of value have been extensively reported in a diverse set of brain regions. However, in many cases it is difficult to determine whether a particular neural response pattern corresponds to a value-signal per se as opposed to an array of alternative non-value related processes, such as outcome-identity coding, informational coding, encoding of autonomic and skeletomotor consequences, alongside previously described “salience” or “attentional” effects. Here, I review a number of experimental manipulations that can be used to test for value, and I identify the challenges in ascertaining whether a particular neural response is or is not a value signal. Finally, I emphasize that some non-value related signals may be especially informative as a means of providing insight into the nature of the decision-making related computations that are being implemented in a particular brain region. PMID:24726573

Foster Mother-Infant Bonding: Associations Between Foster Mothers’ Oxytocin Production, Electrophysiological Brain Activity, Feelings of Commitment, and Caregiving Quality

PubMed Central

Bick, Johanna; Dozier, Mary; Bernard, Kristin; Simons, Robert; Grasso, Damion

2012-01-01

This study examined the biological processes associated with foster mother-infant bonding. In an examination of foster mother-infant dyads (N = 41, mean infant age = 8.5 months), foster mothers’ oxytocin production was associated with their expressions of behavioral delight toward their foster infant and their average P3 response to images of all infant faces in the first two months of the relationship. Three months later, foster mothers’ oxytocin production was still associated with delight toward their foster infant and was also specifically associated with their P3 response to an image of their foster infant. Similar to biologically-related mothers and infants, oxytocin appears to be associated with foster mothers’ brain activity and caregiving behavior, with patterns suggestive of bond formation. PMID:23163703

Shaping the aging brain: role of auditory input patterns in the emergence of auditory cortical impairments

PubMed Central

Kamal, Brishna; Holman, Constance; de Villers-Sidani, Etienne

2013-01-01

Age-related impairments in the primary auditory cortex (A1) include poor tuning selectivity, neural desynchronization, and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function. PMID:24062649

Neurocircuit function in eating disorders.

PubMed

Friederich, Hans-Christoph; Wu, Mudan; Simon, Joe J; Herzog, Wolfgang

2013-07-01

Eating disorders are serious psychosomatic disorders with high morbidity and lifetime mortality. Inadequate response to current therapeutic interventions constitutes a challenging clinical problem. A better understanding of the underlying neurobiological mechanisms could improve psychotherapeutic and drug treatment strategies. A review highlighting the current state of brain imaging in eating disorders related to the anxiety and pathological fear learning model of anorexia nervosa (AN) and the impulsivity model of binge eating in bulimia nervosa (BN). Available neuroimaging studies in patients with acute AN primarily suggest a hyper-responsive emotional and fear network to food, but not necessarily to eating disorder-unrelated, salient stimuli. Furthermore, patients with AN show decreased activation in the ventral fronto-striatal circuits during the performance of a cognitive flexibility task. Results in patients with BN primarily suggest a hypo-responsive reward system to food stimuli, especially to taste reward. Additionally, patients with BN exhibit impaired brain activation in the inhibitory control network during the performance of general response-inhibition tasks. Anxiety and pathological fear learning may lead to conditioned neural stimulus-response patterns to food stimuli and increased cognitive rigidity, which could account for the phobic avoidance of food intake in patients with acute AN. However, further neurobiological studies are required to investigate pathological fear learning in patients with AN. Patients with BN may binge eat to compensate for a hypo-responsive reward system. The impaired brain activation in the inhibitory control network may facilitate the loss of control over food intake in patients with BN. Copyright © 2013 Wiley Periodicals, Inc.

Identification of early and distinct glioblastoma response patterns treated by boron neutron capture therapy not predicted by standard radiographic assessment using functional diffusion map

PubMed Central

2013-01-01

Background Radiologic response of brain tumors is traditionally assessed according to the Macdonald criteria 10 weeks from the start of therapy. Because glioblastoma (GB) responds in days rather than weeks after boron neutron capture therapy (BNCT) that is a form of tumor-selective particle radiation, it is inconvenient to use the Macdonald criteria to assess the therapeutic efficacy of BNCT by gadolinium-magnetic resonance imaging (Gd-MRI). Our study assessed the utility of functional diffusion map (fDM) for evaluating response patterns in GB treated by BNCT. Methods The fDM is an image assessment using time-dependent changes of apparent diffusion coefficient (ADC) in tumors on a voxel-by-voxel approach. Other than time-dependent changes of ADC, fDM can automatically assess minimum/maximum ADC, Response Evaluation Criteria In Solid Tumors (RECIST), and the volume of enhanced lesions on Gd-MRI over time. We assessed 17 GB patients treated by BNCT using fDM. Additionally, in order to verify our results, we performed a histopathological examination using F98 rat glioma models. Results Only the volume of tumor with decreased ADC by fDM at 2 days after BNCT was a good predictor for GB patients treated by BNCT (P value = 0.022 by log-rank test and 0.033 by wilcoxon test). In a histopathological examination, brain sections of F98 rat glioma models treated by BNCT showed cell swelling of both the nuclei and the cytoplasm compared with untreated rat glioma models. Conclusions The fDM could identify response patterns in BNCT-treated GB earlier than a standard radiographic assessment. Early detection of treatment failure can allow a change or supplementation before tumor progression and might lead to an improvement of GB patients’ prognosis. PMID:23915330

Dissociating maternal responses to sad and happy facial expressions of their own child: An fMRI study.

PubMed

Kluczniok, Dorothea; Hindi Attar, Catherine; Stein, Jenny; Poppinga, Sina; Fydrich, Thomas; Jaite, Charlotte; Kappel, Viola; Brunner, Romuald; Herpertz, Sabine C; Boedeker, Katja; Bermpohl, Felix

2017-01-01

Maternal sensitive behavior depends on recognizing one's own child's affective states. The present study investigated distinct and overlapping neural responses of mothers to sad and happy facial expressions of their own child (in comparison to facial expressions of an unfamiliar child). We used functional MRI to measure dissociable and overlapping activation patterns in 27 healthy mothers in response to happy, neutral and sad facial expressions of their own school-aged child and a gender- and age-matched unfamiliar child. To investigate differential activation to sad compared to happy faces of one's own child, we used interaction contrasts. During the scan, mothers had to indicate the affect of the presented face. After scanning, they were asked to rate the perceived emotional arousal and valence levels for each face using a 7-point Likert-scale (adapted SAM version). While viewing their own child's sad faces, mothers showed activation in the amygdala and anterior cingulate cortex whereas happy facial expressions of the own child elicited activation in the hippocampus. Conjoint activation in response to one's own child happy and sad expressions was found in the insula and the superior temporal gyrus. Maternal brain activations differed depending on the child's affective state. Sad faces of the own child activated areas commonly associated with a threat detection network, whereas happy faces activated reward related brain areas. Overlapping activation was found in empathy related networks. These distinct neural activation patterns might facilitate sensitive maternal behavior.

Baseline brain energy supports the state of consciousness.

PubMed

Shulman, Robert G; Hyder, Fahmeed; Rothman, Douglas L

2009-07-07

An individual, human or animal, is defined to be in a conscious state empirically by the behavioral ability to respond meaningfully to stimuli, whereas the loss of consciousness is defined by unresponsiveness. PET measurements of glucose or oxygen consumption show a widespread approximately 45% reduction in cerebral energy consumption with anesthesia-induced loss of consciousness. Because baseline brain energy consumption has been shown by (13)C magnetic resonance spectroscopy to be almost exclusively dedicated to neuronal signaling, we propose that the high level of brain energy is a necessary property of the conscious state. Two additional neuronal properties of the conscious state change with anesthesia. The delocalized fMRI activity patterns in rat brain during sensory stimulation at a higher energy state (close to the awake) collapse to a contralateral somatosensory response at lower energy state (deep anesthesia). Firing rates of an ensemble of neurons in the rat somatosensory cortex shift from the gamma-band range (20-40 Hz) at higher energy state to <10 Hz at lower energy state. With the conscious state defined by the individual's behavior and maintained by high cerebral energy, measurable properties of that state are the widespread fMRI patterns and high frequency neuronal activity, both of which support the extensive interregional communication characteristic of consciousness. This usage of high brain energies when the person is in the "state" of consciousness differs from most studies, which attend the smaller energy increments observed during the stimulations that form the "contents" of that state.

Dynamic Connectivity Patterns in Conscious and Unconscious Brain

PubMed Central

Ma, Yuncong; Hamilton, Christina

2017-01-01

Abstract Brain functional connectivity undergoes dynamic changes from the awake to unconscious states. However, how the dynamics of functional connectivity patterns are linked to consciousness at the behavioral level remains elusive. In this study, we acquired resting-state functional magnetic resonance imaging data during wakefulness and graded levels of consciousness in rats. Data were analyzed using a dynamic approach combining the sliding window method and k-means clustering. Our results demonstrate that whole-brain networks contained several quasi-stable patterns that dynamically recurred from the awake state into anesthetized states. Remarkably, two brain connectivity states with distinct spatial similarity to the structure of anatomical connectivity were strongly biased toward high and low consciousness levels, respectively. These results provide compelling neuroimaging evidence linking the dynamics of whole-brain functional connectivity patterns and states of consciousness at the behavioral level. PMID:27846731

Response to traumatic brain injury neurorehabilitation through an artificial intelligence and statistics hybrid knowledge discovery from databases methodology.

PubMed

Gibert, Karina; García-Rudolph, Alejandro; García-Molina, Alberto; Roig-Rovira, Teresa; Bernabeu, Montse; Tormos, José María

2008-01-01

Develop a classificatory tool to identify different populations of patients with Traumatic Brain Injury based on the characteristics of deficit and response to treatment. A KDD framework where first, descriptive statistics of every variable was done, data cleaning and selection of relevant variables. Then data was mined using a generalization of Clustering based on rules (CIBR), an hybrid AI and Statistics technique which combines inductive learning (AI) and clustering (Statistics). A prior Knowledge Base (KB) is considered to properly bias the clustering; semantic constraints implied by the KB hold in final clusters, guaranteeing interpretability of the resultis. A generalization (Exogenous Clustering based on rules, ECIBR) is presented, allowing to define the KB in terms of variables which will not be considered in the clustering process itself, to get more flexibility. Several tools as Class panel graph are introduced in the methodology to assist final interpretation. A set of 5 classes was recommended by the system and interpretation permitted profiles labeling. From the medical point of view, composition of classes is well corresponding with different patterns of increasing level of response to rehabilitation treatments. All the patients initially assessable conform a single group. Severe impaired patients are subdivided in four profiles which clearly distinct response patterns. Particularly interesting the partial response profile, where patients could not improve executive functions. Meaningful classes were obtained and, from a semantics point of view, the results were sensibly improved regarding classical clustering, according to our opinion that hybrid AI & Stats techniques are more powerful for KDD than pure ones.

Two Parallel Olfactory Pathways for Processing General Odors in a Cockroach

PubMed Central

Watanabe, Hidehiro; Nishino, Hiroshi; Mizunami, Makoto; Yokohari, Fumio

2017-01-01

In animals, sensory processing via parallel pathways, including the olfactory system, is a common design. However, the mechanisms that parallel pathways use to encode highly complex and dynamic odor signals remain unclear. In the current study, we examined the anatomical and physiological features of parallel olfactory pathways in an evolutionally basal insect, the cockroach Periplaneta americana. In this insect, the entire system for processing general odors, from olfactory sensory neurons to higher brain centers, is anatomically segregated into two parallel pathways. Two separate populations of secondary olfactory neurons, type1 and type2 projection neurons (PNs), with dendrites in distinct glomerular groups relay olfactory signals to segregated areas of higher brain centers. We conducted intracellular recordings, revealing olfactory properties and temporal patterns of both types of PNs. Generally, type1 PNs exhibit higher odor-specificities to nine tested odorants than type2 PNs. Cluster analyses revealed that odor-evoked responses were temporally complex and varied in type1 PNs, while type2 PNs exhibited phasic on-responses with either early or late latencies to an effective odor. The late responses are 30–40 ms later than the early responses. Simultaneous intracellular recordings from two different PNs revealed that a given odor activated both types of PNs with different temporal patterns, and latencies of early and late responses in type2 PNs might be precisely controlled. Our results suggest that the cockroach is equipped with two anatomically and physiologically segregated parallel olfactory pathways, which might employ different neural strategies to encode odor information. PMID:28529476

Dexamethasone increases production of C-type natriuretic peptide in the sheep brain.

PubMed

Wilson, Michele O; McNeill, Bryony A; Barrell, Graham K; Prickett, Timothy C R; Espiner, Eric A

2017-10-01

Although C-type natriuretic peptide (CNP) has high abundance in brain tissues and cerebrospinal fluid (CSF), the source and possible factors regulating its secretion within the central nervous system (CNS) are unknown. Here we report the dynamic effects of a single IV bolus of dexamethasone or saline solution on plasma, CSF, CNS and pituitary tissue content of CNP products in adult sheep, along with changes in CNP gene expression in selected tissues. Both CNP and NTproCNP (the amino-terminal product of proCNP) in plasma and CSF showed dose-responsive increases lasting 12-16 h after dexamethasone, whereas other natriuretic peptides were unaffected. CNS tissue concentrations of CNP and NTproCNP were increased by dexamethasone in all of the 12 regions examined. Abundance was highest in limbic tissues, pons and medulla oblongata. Relative to controls, CNP gene expression ( NPPC ) was upregulated by dexamethasone in 5 of 7 brain tissues examined. Patterns of responses differed in pituitary tissue. Whereas the abundance of CNP in both lobes of the pituitary gland greatly exceeded that of brain tissues, neither CNP nor NTproCNP concentration was affected by dexamethasone, despite an increase in NPPC expression. This is the first report of enhanced production and secretion of CNP in brain tissues in response to a corticosteroid. Activation of CNP secretion within CNS tissues by dexamethasone, not exhibited by other natriuretic peptides, suggests an important role for CNP in settings of acute stress. Differential findings in pituitary tissues likely relate to altered processing of proCNP storage and secretion. © 2017 Society for Endocrinology.

Brain responses to bladder filling in older women without urgency incontinence.

PubMed

Tadic, Stasa D; Tannenbaum, Cara; Resnick, Neil M; Griffiths, Derek

2013-06-01

To investigate normal brain responses to bladder filling, especially when there is little or no sensation as in much of daily life. We performed an functional magnetic resonance imaging (fMRI) study of brain responses to bladder filling in normal female subjects, evoked by infusion and withdrawal of fluid in and out of the bladder. Using the contrast (infusion-withdrawal), we imaged brain activity at small bladder volumes with weak filling sensation and also with full bladder and strong desire to void. Eleven women, average age 65 years (range: 60-71 years) were included. With full bladder and strong desire to void, filling provoked a well-known pattern of activation near the right insula and (as a trend) in the dorsal anterior cingulate cortex and supplementary motor area. There was no significant deactivation. With small bladder volume filling provoked widespread apparent deactivation and no significant activation. Apparent deactivation was associated with increased fMRI signal during withdrawal rather than decrease during infusion, suggesting artifact. A correction for global changes in cerebral blood flow eliminated it and revealed significant subcortical activation, although none in frontal or parietal cortex. In older women with normal bladder function, infusion into an already full bladder resulted in strong sensation and brain activation near the insula and in the dorsal anterior cingulate/supplementary motor complex. With near-empty bladder and little sensation, the situation during much of daily life, these cortical areas were not detectably activated, but activation in midbrain and parahippocampal regions presumably indicated unconscious monitoring of ascending bladder signals. Copyright © 2013 Wiley Periodicals, Inc.

On Expression Patterns and Developmental Origin of Human Brain Regions.

PubMed

Kirsch, Lior; Chechik, Gal

2016-08-01

Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions.

On Expression Patterns and Developmental Origin of Human Brain Regions

PubMed Central

Kirsch, Lior; Chechik, Gal

2016-01-01

Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions. PMID:27564987

Optimized temporal pattern of brain stimulation designed by computational evolution

PubMed Central

Brocker, David T.; Swan, Brandon D.; So, Rosa Q.; Turner, Dennis A.; Gross, Robert E.; Grill, Warren M.

2017-01-01

Brain stimulation is a promising therapy for several neurological disorders, including Parkinson’s disease. Stimulation parameters are selected empirically and are limited to the frequency and intensity of stimulation. We used the temporal pattern of stimulation as a novel parameter of deep brain stimulation to ameliorate symptoms in a parkinsonian animal model and in humans with Parkinson’s disease. We used model-based computational evolution to optimize the stimulation pattern. The optimized pattern produced symptom relief comparable to that from standard high-frequency stimulation (a constant rate of 130 or 185 Hz) and outperformed frequency-matched standard stimulation in the parkinsonian rat and in patients. Both optimized and standard stimulation suppressed abnormal oscillatory activity in the basal ganglia of rats and humans. The results illustrate the utility of model-based computational evolution to design temporal pattern of stimulation to increase the efficiency of brain stimulation in Parkinson’s disease, thereby requiring substantially less energy than traditional brain stimulation. PMID:28053151

Structural whole-brain covariance of the anterior and posterior hippocampus: Associations with age and memory.

PubMed

Nordin, Kristin; Persson, Jonas; Stening, Eva; Herlitz, Agneta; Larsson, Elna-Marie; Söderlund, Hedvig

2018-02-01

The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole-brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole-brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole-brain covariance of the HC in addition to regional volume, in young, middle-aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior-specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single-item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole-brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age-related alterations. © 2017 Wiley Periodicals, Inc.

Electroconvulsive therapy-induced brain functional connectivity predicts therapeutic efficacy in patients with schizophrenia: a multivariate pattern recognition study.

PubMed

Li, Peng; Jing, Ri-Xing; Zhao, Rong-Jiang; Ding, Zeng-Bo; Shi, Le; Sun, Hong-Qiang; Lin, Xiao; Fan, Teng-Teng; Dong, Wen-Tian; Fan, Yong; Lu, Lin

2017-05-11

Previous studies suggested that electroconvulsive therapy can influence regional metabolism and dopamine signaling, thereby alleviating symptoms of schizophrenia. It remains unclear what patients may benefit more from the treatment. The present study sought to identify biomarkers that predict the electroconvulsive therapy response in individual patients. Thirty-four schizophrenia patients and 34 controls were included in this study. Patients were scanned prior to treatment and after 6 weeks of treatment with antipsychotics only (n = 16) or a combination of antipsychotics and electroconvulsive therapy (n = 13). Subject-specific intrinsic connectivity networks were computed for each subject using a group information-guided independent component analysis technique. Classifiers were built to distinguish patients from controls and quantify brain states based on intrinsic connectivity networks. A general linear model was built on the classification scores of first scan (referred to as baseline classification scores) to predict treatment response. Classifiers built on the default mode network, the temporal lobe network, the language network, the corticostriatal network, the frontal-parietal network, and the cerebellum achieved a cross-validated classification accuracy of 83.82%, with specificity of 91.18% and sensitivity of 76.47%. After the electroconvulsive therapy, psychosis symptoms of the patients were relieved and classification scores of the patients were decreased. Moreover, the baseline classification scores were predictive for the treatment outcome. Schizophrenia patients exhibited functional deviations in multiple intrinsic connectivity networks which were able to distinguish patients from healthy controls at an individual level. Patients with lower classification scores prior to treatment had better treatment outcome, indicating that the baseline classification scores before treatment is a good predictor for treatment outcome. CONNECTIVITY NETWORKS REVEAL GOOD CANDIDATES FOR BRAIN STIMULATION: Connectivity patterns in the brain may help identify patients with schizophrenia most likely to benefit from electroconvulsive therapy. A team led by Lin Lu from Peking University, China, and Yong Fan from the University of Pennsylvania, USA, took functional magnetic resonance imaging (MRI) scans of 34 people with schizophrenia and 34 control individuals without mental illness. Those with schizophrenia were scanned before and after treatment; some received antipsychotics alone, others received medication plus electroconvulsive therapy. The researchers created organizational brain maps known as "intrinsic connectivity networks" for each individual, and showed that the neuroimaging pattern could discriminate between people with and without schizophrenia. For the schizophrenia patients, the connectivity networks taken prior to treatment also helped predict who would benefit from the brain-stimulation procedure. Such a biomarker could prove a useful diagnostic tool for clinicians.

Determination of Vascular Dementia Brain in Distinct Frequency Bands with Whole Brain Functional Connectivity Patterns

PubMed Central

Zhang, Delong; Liu, Bo; Chen, Jun; Peng, Xiaoling; Liu, Xian; Fan, Yuanyuan; Liu, Ming; Huang, Ruiwang

2013-01-01

Recent studies have shown that multivariate pattern analysis (MVPA) can be useful for distinguishing brain disorders into categories. Such analyses can substantially enrich and facilitate clinical diagnoses. Using MPVA methods, whole brain functional networks, especially those derived using different frequency windows, can be applied to detect brain states. We constructed whole brain functional networks for groups of vascular dementia (VaD) patients and controls using resting state BOLD-fMRI (rsfMRI) data from three frequency bands - slow-5 (0.01∼0.027 Hz), slow-4 (0.027∼0.073 Hz), and whole-band (0.01∼0.073 Hz). Then we used the support vector machine (SVM), a type of MVPA classifier, to determine the patterns of functional connectivity. Our results showed that the brain functional networks derived from rsfMRI data (19 VaD patients and 20 controls) in these three frequency bands appear to reflect neurobiological changes in VaD patients. Such differences could be used to differentiate the brain states of VaD patients from those of healthy individuals. We also found that the functional connectivity patterns of the human brain in the three frequency bands differed, as did their ability to differentiate brain states. Specifically, the ability of the functional connectivity pattern to differentiate VaD brains from healthy ones was more efficient in the slow-5 (0.01∼0.027 Hz) band than in the other two frequency bands. Our findings suggest that the MVPA approach could be used to detect abnormalities in the functional connectivity of VaD patients in distinct frequency bands. Identifying such abnormalities may contribute to our understanding of the pathogenesis of VaD. PMID:23359801

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.

151. Bromocriptine Challenge Affects Working Memory Processing in Humans Depending on DRD2-Related Genes

PubMed Central

Pergola, Giulio; Selvaggi, Pierluigi; Gelao, Barbara; Di Carlo, Pasquale; Nettis, Maria Antonietta; Amico, Graziella; Felici, Valentina; Fazio, Leonardo; Rampino, Antonio; Sambataro, Fabio; Blasi, Giuseppe; Bertolino, Alessandro

2017-01-01

Abstract Background: Dopamine D2 receptors (D2R) contribute to the inverted-U shaped relationship between dopamine dorsolateral prefrontal cortex (DLPFC) and working memory (WM). Genetic variation in DRD2 coding for D2Rs modulates D2 signaling, but other genes in its pathway may be involved. In a previous work, using gene co-expression networks we identified 84 partner genes coregulated with DRD2 and eight single nucleotide polymorphisms (SNPs) predicting coexpression of the whole gene set in the human DLPFC [1]. These SNPs combined into a polygenic coexpression index (PCI) predicted WM performance and DLPFC activity in two independent samples of living healthy humans [1]. Here, we asked whether response to D2R targeting drugs is associated with this PCI. Thus, we investigated the interaction between WM behavioral/brain response to the D2R agonist Bromocriptine (BRO) and the PCI. [1] Pergola G, Di Carlo P, et al. (In press). Translational Psychiatry. Methods: Fifty healthy volunteers entered a double-blind, crossover, randomized, placebo-controlled fMRI study with BRO 1.25 mg and performed the N-Back WM task during the fMRI scanning session. We computed the PCI for all participants and investigated its association with WM-related behavior and brain activity using general linear models. Results: A PCI by drug interaction was significant on both DLPFC signal (right BA46, 242 voxels, F(1, 48) = 24; right BA9, 177 voxels, F(1, 48) = 19; P < .05 cluster-level FWE corrected) and behavioral scores, F(1, 46) = 4.6, P = .045, using a U-shaped quadratic model. The U-shaped relationship between the PCI and WM processing found on placebo was reversed on BRO. Furthermore, the increase in behavioral performance on BRO correlated with a decrease in BA46 activity, t(48) = −2.0, P = .049). Conclusion: The combined effect of multiple alleles on DRD2 coexpression covaried with drug response such that different allelic patterns were associated with similar responses, as in the inverted U-shaped model of WM. Thus, multiple genes and multiple allelic patterns are implicated in the inverted U-shaped dopamine/WM relationship. This relationship is reversed when individuals are administered BRO, suggesting that brain and behavioral response to this pharmacological challenge depends on a pleiotropic individual genetic background. Hence, pharmacogenomics in schizophrenia should take into account allelic patterns associated with molecular phenomena such as gene expression to predict drug response.

Audiovisual synchrony enhances BOLD responses in a brain network including multisensory STS while also enhancing target-detection performance for both modalities

PubMed Central

Marchant, Jennifer L; Ruff, Christian C; Driver, Jon

2012-01-01

The brain seeks to combine related inputs from different senses (e.g., hearing and vision), via multisensory integration. Temporal information can indicate whether stimuli in different senses are related or not. A recent human fMRI study (Noesselt et al. [2007]: J Neurosci 27:11431–11441) used auditory and visual trains of beeps and flashes with erratic timing, manipulating whether auditory and visual trains were synchronous or unrelated in temporal pattern. A region of superior temporal sulcus (STS) showed higher BOLD signal for the synchronous condition. But this could not be related to performance, and it remained unclear if the erratic, unpredictable nature of the stimulus trains was important. Here we compared synchronous audiovisual trains to asynchronous trains, while using a behavioral task requiring detection of higher-intensity target events in either modality. We further varied whether the stimulus trains had predictable temporal pattern or not. Synchrony (versus lag) between auditory and visual trains enhanced behavioral sensitivity (d') to intensity targets in either modality, regardless of predictable versus unpredictable patterning. The analogous contrast in fMRI revealed BOLD increases in several brain areas, including the left STS region reported by Noesselt et al. [2007: J Neurosci 27:11431–11441]. The synchrony effect on BOLD here correlated with the subject-by-subject impact on performance. Predictability of temporal pattern did not affect target detection performance or STS activity, but did lead to an interaction with audiovisual synchrony for BOLD in inferior parietal cortex. PMID:21953980

Search for Patterns of Functional Specificity in the Brain: A Nonparametric Hierarchical Bayesian Model for Group fMRI Data

PubMed Central

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

2012-01-01

Functional MRI studies have uncovered a number of brain areas that demonstrate highly specific functional patterns. In the case of visual object recognition, small, focal regions have been characterized with selectivity for visual categories such as human faces. In this paper, we develop an algorithm that automatically learns patterns of functional specificity from fMRI data in a group of subjects. The method does not require spatial alignment of functional images from different subjects. The 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 sets of activation variables in all subjects. We use a Hierarchical Dirichlet Process as the prior in order to learn the patterns of functional specificity shared across the group, which we call functional systems, and estimate the number of these systems. Inference based on our model enables automatic discovery and characterization of dominant and consistent functional systems. We apply the method to data from a visual fMRI study comprised of 69 distinct stimulus images. The discovered system activation profiles correspond to selectivity for a number of image categories such as faces, bodies, and scenes. Among systems found by our method, we identify new areas that are deactivated by face stimuli. In empirical comparisons with perviously proposed exploratory methods, our results appear superior in capturing the structure in the space of visual categories of stimuli. PMID:21884803

Model of the transient neurovascular response based on prompt arterial dilation

PubMed Central

Kim, Jung Hwan; Khan, Reswanul; Thompson, Jeffrey K; Ress, David

2013-01-01

Brief neural stimulation results in a stereotypical pattern of vascular and metabolic response that is the basis for popular brain-imaging methods such as functional magnetic resonance imagine. However, the mechanisms of transient oxygen transport and its coupling to cerebral blood flow (CBF) and oxygen metabolism (CMRO2) are poorly understood. Recent experiments show that brief stimulation produces prompt arterial vasodilation rather than venous vasodilation. This work provides a neurovascular response model for brief stimulation based on transient arterial effects using one-dimensional convection–diffusion transport. Hemoglobin oxygen dissociation is included to enable predictions of absolute oxygen concentrations. Arterial CBF response is modeled using a lumped linear flow model, and CMRO2 response is modeled using a gamma function. Using six parameters, the model successfully fit 161/166 measured extravascular oxygen time courses obtained for brief visual stimulation in cat cerebral cortex. Results show how CBF and CMRO2 responses compete to produce the observed features of the hemodynamic response: initial dip, hyperoxic peak, undershoot, and ringing. Predicted CBF and CMRO2 response amplitudes are consistent with experimental measurements. This model provides a powerful framework to quantitatively interpret oxygen transport in the brain; in particular, its intravascular oxygen concentration predictions provide a new model for fMRI responses. PMID:23756690

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

PubMed

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

2017-07-01

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

Group-level spatio-temporal pattern recovery in MEG decoding using multi-task joint feature learning.

PubMed

Kia, Seyed Mostafa; Pedregosa, Fabian; Blumenthal, Anna; Passerini, Andrea

2017-06-15

The use of machine learning models to discriminate between patterns of neural activity has become in recent years a standard analysis approach in neuroimaging studies. Whenever these models are linear, the estimated parameters can be visualized in the form of brain maps which can aid in understanding how brain activity in space and time underlies a cognitive function. However, the recovered brain maps often suffer from lack of interpretability, especially in group analysis of multi-subject data. To facilitate the application of brain decoding in group-level analysis, we present an application of multi-task joint feature learning for group-level multivariate pattern recovery in single-trial magnetoencephalography (MEG) decoding. The proposed method allows for recovering sparse yet consistent patterns across different subjects, and therefore enhances the interpretability of the decoding model. Our experimental results demonstrate that the mutli-task joint feature learning framework is capable of recovering more meaningful patterns of varying spatio-temporally distributed brain activity across individuals while still maintaining excellent generalization performance. We compare the performance of the multi-task joint feature learning in terms of generalization, reproducibility, and quality of pattern recovery against traditional single-subject and pooling approaches on both simulated and real MEG datasets. These results can facilitate the usage of brain decoding for the characterization of fine-level distinctive patterns in group-level inference. Considering the importance of group-level analysis, the proposed approach can provide a methodological shift towards more interpretable brain decoding models. Copyright © 2017 Elsevier B.V. All rights reserved.

The Neural Basis of Maternal Bonding

PubMed Central

Wan, Ming Wai; Downey, Darragh; Strachan, Hilary; Elliott, Rebecca; Williams, Steve R.; Abel, Kathryn M.

2014-01-01

Background Accumulating evidence suggests that mothers show a different pattern of brain responses when viewing their own compared to other infants. However, there is inconsistency across functional imaging studies regarding the key areas involved, and none have examined relationships between brain and behavioural responses to infants. We examined the brain regions activated when mothers viewed videos of their own infant contrasted with an unknown infant, and whether these are associated with behavioural and self-reported measures of mother-infant relations. Method Twenty right-handed mothers viewed alternating 30-sec blocks of video of own 4–9 month infant and an unfamiliar matched infant, interspersed with neutral video. Whole brain functional magnetic resonance images (fMRI) were acquired on a 1.5T Philips Intera scanner using a TR of 2.55 s. Videotaped mother-infant interactions were systematically evaluated blind to family information to generate behavioural measures for correlational analysis. Results Enhanced blood oxygenation functional imaging responses were found in the own versus unknown infant contrast in the bilateral precuneus, right superior temporal gyrus, right medial and left middle frontal gyri and left amygdala. Positive mother-infant interaction (less directive parent behaviour; more positive/attentive infant behaviour) was significantly associated with greater activation in several regions on viewing own versus unknown infant, particularly the middle frontal gyrus. Mothers' perceived warmth of her infant was correlated with activations in the same contrast, particularly in sensory and visual areas. Conclusion This study partially replicates previous reports of the brain regions activated in mothers in response to the visual presentation of their own infant. It is the first to report associations between mothers' unique neural responses to viewing their own infant with the quality of her concurrent behaviour when interacting with her infant and with her perceptions of infant warmth. These findings provide support for developing fMRI as a potential biomarker of parenting risk and change. PMID:24594508

The Yin and Yang of innate immunity in stroke.

PubMed

Xu, Xiaomeng; Jiang, Yongjun

2014-01-01

Immune system plays an elementary role in the pathophysiological progress of ischemic stroke. It consists of innate and adaptive immune system. Activated within minutes after ischemic onset, innate immunity is responsible for the elimination of necrotic cells and tissue repair, while it is critically involved in the initiation and amplification of poststroke inflammation that amplifies ischemic damage to the brain tissue. Innate immune response requires days to be fully developed, providing a considerable time window for therapeutic intervention, suggesting prospect of novel immunomodulatory therapies against poststroke inflammation-induced brain injury. However, obstacles still exist and a comprehensive understanding of ischemic stroke and innate immune reaction is essential. In this review, we highlighted the current experimental and clinical data depicting the innate immune response following ischemic stroke, mainly focusing on the recognition of damage-associated molecular patterns, activation and recruitment of innate immune cells, and involvement of various cytokines. In addition, clinical trials targeting innate immunity were also documented regardless of the outcome, stressing the requirements for further investigation.

When the threat comes from inside the body: a neuroscience based learning perspective of the etiology of panic disorder.

PubMed

Hamm, Alfons O; Richter, Jan; Pané-Farré, Christiane A

2014-01-01

Unexpected, recurrent panic attacks and anxious apprehension are two distinct emotional phenomena that constitute the core symptoms for diagnosing panic disorder. Taking a neuroscience perspective the current review paper presents both epidemiological and experimental psychophysiological evidence suggesting that panic attacks can be conceptualized as an unconditioned circa defense response pattern to intense internal threat stimuli, characterized by strong autonomic surge and escape behavior and abnormal plastic changes of the brain. Anxious apprehension develops after the experience of such severe panic attacks as conditioned responses to mild body symptoms. Theoretically these conditioned fear responses can be considered as post-encounter defense characterized by increased selective attention, increased threat appraisal and defensive freezing and startle potentiation evidencing altered brain circuits evoked by mild body symptoms. Agoraphobic avoidance starts very early during the defensive cascade and can be conceived as motivated behavior driven by the incentive to be in a safe context that is under control of the individual.

Circadian genes, the stress axis, and alcoholism.

PubMed

Sarkar, Dipak K

2012-01-01

The body's internal system to control the daily rhythm of the body's functions (i.e., the circadian system), the body's stress response, and the body's neurobiology are highly interconnected. Thus, the rhythm of the circadian system impacts alcohol use patterns; at the same time, alcohol drinking also can alter circadian functions. The sensitivity of the circadian system to alcohol may result from alcohol's effects on the expression of several of the clock genes that regulate circadian function. The stress response system involves the hypothalamus and pituitary gland in the brain and the adrenal glands, as well as the hormones they secrete, including corticotrophin-releasing hormone, adrenocorticotrophic hormone, and glucocorticoids. It is controlled by brain-signaling molecules, including endogenous opioids such as β-endorphin. Alcohol consumption influences the activity of this system and vice versa. Finally, interactions exist between the circadian system, the hypothalamic-pituitary-adrenal axis, and alcohol consumption. Thus, it seems that certain clock genes may control functions of the stress response system and that these interactions are affected by alcohol.

Differential DNA damage in response to the neonatal and adult excitotoxic hippocampal lesion in rats.

PubMed

Khaing, Z Z; Weickert, C S; Weinberger, D R; Lipska, B K

2000-12-01

We examined the developmental profile of excitotoxin-induced nuclear DNA fragmentation using the transferase dUTP nick-end labelling (TUNEL) technique, as a marker of DNA damage and cell death in rats with neonatal and adult excitotoxic lesions of the ventral hippocampus. We hypothesized that infusion of neurotoxin may result in a differential pattern of cell death in neonatally and adult lesioned rats, both in the infusion site and in remote brain regions presumably involved in mediating behavioural changes observed in these animals. Brains of rats lesioned at 7 days of age and in adulthood were collected at several survival times 1-21 days after the lesion. In the lesioned neonates 1-3 days postlesion, marked increases in TUNEL-positive cells occurred in the ventral hippocampus, the site of neurotoxin infusion, and in a wide surrounding area. Adult lesioned brains showed more positive cells than controls only at the infusion site. In the lesioned neonates, TUNEL-labelled cells were also present in the striatum and nucleus accumbens 1 day postlesion but not at later survival times. Our findings indicate that cell death in remote regions is more prominent in immature than adult brains, that it may lead to distinct alterations in development of these brain regions, and thus may be responsible for functional differences between neonatally and adult lesioned rats.

Temporal Profiles Dissociate Regional Extracellular Ethanol versus Dopamine Concentrations

PubMed Central

2015-01-01

In vivo monitoring of dopamine via microdialysis has demonstrated that acute, systemic ethanol increases extracellular dopamine in regions innervated by dopaminergic neurons originating in the ventral tegmental area and substantia nigra. Simultaneous measurement of dialysate dopamine and ethanol allows comparison of the time courses of their extracellular concentrations. Early studies demonstrated dissociations between the time courses of brain ethanol concentrations and dopaminergic responses in the nucleus accumbens (NAc) elicited by acute ethanol administration. Both brain ethanol and extracellular dopamine levels peak during the first 5 min following systemic ethanol administration, but the dopamine response returns to baseline while brain ethanol concentrations remain elevated. Post hoc analyses examined ratios of the dopamine response (represented as a percent above baseline) to tissue concentrations of ethanol at different time points within the first 25–30 min in the prefrontal cortex, NAc core and shell, and dorsomedial striatum following a single intravenous infusion of ethanol (1 g/kg). The temporal patterns of these “response ratios” differed across brain regions, possibly due to regional differences in the mechanisms underlying the decline of the dopamine signal associated with acute intravenous ethanol administration and/or to the differential effects of acute ethanol on the properties of subpopulations of midbrain dopamine neurons. This Review draws on neurochemical, physiological, and molecular studies to summarize the effects of acute ethanol administration on dopamine activity in the prefrontal cortex and striatal regions, to explore the potential reasons for the regional differences observed in the decline of ethanol-induced dopamine signals, and to suggest directions for future research. PMID:25537116

Stressed (acute) mice display neuroimmunodysregulation and defective innate immune response against coliform infection.

PubMed

Mehrzad, Jalil; Shajari, Majid; Saleh-Moghaddam, Massoud; Sarmad-Nabavi, Mohammad

2015-09-01

We examined the impact of acute restraint stress (ARS) with(out) intraperitoneal E. coli infection on TLR4 mRNA abundance in brain and spleen, clinical signs, cytokines and oxidative loads and peritoneal E. coli growth in balb/c mice. ARS exacerbated E. coli virulence and behavioral abnormality. At different post-stress hour the pattern and intensity of TLR4 activity differed in brain and spleen. While TLR4 stimulation in spleen of E. coli-infected mice was maximal, it superseded in brain of post-stressed E. coli-infected mice. ARS and E. coli infection elicited systemic pro-inflammatory and pro-oxidant status, with defective peritoneal E. coli clearance in post-ARS mice. Continuous TLR4 activation in post-stressed mice partially disarms innate immune response, and contributes to inappropriate host-E. coli interactions and thus neuroimmune dysregulation/toxicity. The description of these observed novel effects induced by ARS will provide a basis for deeper investigations of the effects from increasingly stress-oriented rural/urban life upon neuroimmune system. Copyright © 2015 Elsevier B.V. All rights reserved.

The motivation to control and the origin of mind: exploring the life-mind joint point in the Tree of Knowledge System.

PubMed

Geary, David C

2005-01-01

The evolved function of brain, cognitive, affective, conscious-psychological, and behavioral systems is to enable animals to attempt to gain control of the social (e.g., mates), biological (e.g., prey), and physical (e.g., nesting spots) resources that have tended to covary with survival and reproductive outcomes during the species' evolutionary history. These resources generate information patterns that range from invariant to variant. Invariant information is consistent across generations and within lifetimes (e.g., the prototypical shape of a human face) and is associated with modular brain and cognitive systems that coalesce around the domains of folk psychology, folk biology, and folk physics. The processing of information in these domains is implicit and results in automatic bottom-up behavioral responses. Variant information varies across generations and within lifetimes (e.g., as in social dynamics) and is associated with plastic brain and cognitive systems and explicit, consciously driven top-down behavioral responses. The fundamentals of this motivation-to-control model are outlined and links are made to Henriques' (2004) Tree of Knowledge System and Behavioral Investment Theory.

Task positive and default mode networks during a working memory in children with primary monosymptomatic nocturnal enuresis and healthy controls.

PubMed

Zhang, Kaihua; Ma, Jun; Lei, Du; Wang, Mengxing; Zhang, Jilei; Du, Xiaoxia

2015-10-01

Nocturnal enuresis is a common developmental disorder in children, and primary monosymptomatic nocturnal enuresis (PMNE) is the dominant subtype. This study investigated brain functional abnormalities that are specifically related to working memory in children with PMNE using function magnetic resonance imaging (fMRI) in combination with an n-back task. Twenty children with PMNE and 20 healthy children, group-matched for age and sex, participated in this experiment. Several brain regions exhibited reduced activation during the n-back task in children with PMNE, including the right precentral gyrus and the right inferior parietal lobule extending to the postcentral gyrus. Children with PMNE exhibited decreased cerebral activation in the task-positive network, increased task-related cerebral deactivation during a working memory task, and longer response times. Patients exhibited different brain response patterns to different levels of working memory and tended to compensate by greater default mode network deactivation to sustain normal working memory function. Our results suggest that children with PMNE have potential working memory dysfunction.

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

PubMed Central

Danese, Andrea; J Lewis, Stephanie

2017-01-01

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

Developmental differences in the neural mechanisms of facial emotion labeling

PubMed Central

Adleman, Nancy E.; Kim, Pilyoung; Oakes, Allison H.; Hsu, Derek; Reynolds, Richard C.; Chen, Gang; Pine, Daniel S.; Brotman, Melissa A.; Leibenluft, Ellen

2016-01-01

Adolescence is a time of increased risk for the onset of psychological disorders associated with deficits in face emotion labeling. We used functional magnetic resonance imaging (fMRI) to examine age-related differences in brain activation while adolescents and adults labeled the emotion on fearful, happy and angry faces of varying intensities [0% (i.e. neutral), 50%, 75%, 100%]. Adolescents and adults did not differ on accuracy to label emotions. In the superior temporal sulcus, ventrolateral prefrontal cortex and middle temporal gyrus, adults show an inverted-U-shaped response to increasing intensities of fearful faces and a U-shaped response to increasing intensities of happy faces, whereas adolescents show the opposite patterns. In addition, adults, but not adolescents, show greater inferior occipital gyrus activation to negative (angry, fearful) vs positive (happy) emotions. In sum, when subjects classify subtly varying facial emotions, developmental differences manifest in several ‘ventral stream’ brain regions. Charting the typical developmental course of the brain mechanisms of socioemotional processes, such as facial emotion labeling, is an important focus for developmental psychopathology research. PMID:26245836

Amplitude-integrated EEG in newborns with critical congenital heart disease predicts preoperative brain magnetic resonance imaging findings.

PubMed

Mulkey, Sarah B; Yap, Vivien L; Bai, Shasha; Ramakrishnaiah, Raghu H; Glasier, Charles M; Bornemeier, Renee A; Schmitz, Michael L; Bhutta, Adnan T

2015-06-01

The study aims are to evaluate cerebral background patterns using amplitude-integrated electroencephalography in newborns with critical congenital heart disease, determine if amplitude-integrated electroencephalography is predictive of preoperative brain injury, and assess the incidence of preoperative seizures. We hypothesize that amplitude-integrated electroencephalography will show abnormal background patterns in the early preoperative period in infants with congenital heart disease that have preoperative brain injury on magnetic resonance imaging. Twenty-four newborns with congenital heart disease requiring surgery at younger than 30 days of age were prospectively enrolled within the first 3 days of age at a tertiary care pediatric hospital. Infants had amplitude-integrated electroencephalography for 24 hours beginning close to birth and preoperative brain magnetic resonance imaging. The amplitude-integrated electroencephalographies were read to determine if the background pattern was normal, mildly abnormal, or severely abnormal. The presence of seizures and sleep-wake cycling were noted. The preoperative brain magnetic resonance imaging scans were used for brain injury and brain atrophy assessment. Fifteen of 24 infants had abnormal amplitude-integrated electroencephalography at 0.71 (0-2) (mean [range]) days of age. In five infants, the background pattern was severely abnormal. (burst suppression and/or continuous low voltage). Of the 15 infants with abnormal amplitude-integrated electroencephalography, 9 (60%) had brain injury. One infant with brain injury had a seizure on amplitude-integrated electroencephalography. A severely abnormal background pattern on amplitude-integrated electroencephalography was associated with brain atrophy (P = 0.03) and absent sleep-wake cycling (P = 0.022). Background cerebral activity is abnormal on amplitude-integrated electroencephalography following birth in newborns with congenital heart disease who have findings of brain injury and/or brain atrophy on preoperative brain magnetic resonance imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury.

PubMed

Tu, Tsang-Wei; Lescher, Jacob D; Williams, Rashida A; Jikaria, Neekita; Turtzo, L Christine; Frank, Joseph A

2017-01-01

Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate the interpretation of imaging and IHC observations.

Abnormal Injury Response in Spontaneous Mild Ventriculomegaly Wistar Rat Brains: A Pathological Correlation Study of Diffusion Tensor and Magnetization Transfer Imaging in Mild Traumatic Brain Injury

PubMed Central

Lescher, Jacob D.; Williams, Rashida A.; Jikaria, Neekita; Turtzo, L. Christine; Frank, Joseph A.

2017-01-01

Abstract Spontaneous mild ventriculomegaly (MVM) was previously reported in ∼43% of Wistar rats in association with vascular anomalies without phenotypic manifestation. This mild traumatic brain injury (TBI) weight drop model study investigates whether MVM rats (n = 15) have different injury responses that could inadvertently complicate the interpretation of imaging studies compared with normal rats (n = 15). Quantitative MRI, including diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI), and immunohistochemistry (IHC) analysis were used to examine the injury pattern up to 8 days post-injury in MVM and normal rats. Prior to injury, the MVM brain showed significant higher mean diffusivity, axial diffusivity, and radial diffusivity, and lower fractional anisotropy (FA) and magnetization transfer ratio (MTR) in the corpus callosum than normal brain (p < 0.05). Following TBI, normal brains exhibited significant decreases of FA in the corpus callosum, whereas MVM brains demonstrated insignificant changes in FA, suggesting less axonal injury. At day 8 after mild TBI, MTR of the normal brains significantly decreased whereas the MTR of the MVM brains significantly increased. IHC staining substantiated the MRI findings, demonstrating limited axonal injury with significant increase of microgliosis and astrogliosis in MVM brain compared with normal animals. The radiological-pathological correlation data showed that both DTI and MTI were sensitive in detecting mild diffuse brain injury, although DTI metrics were more specific in correlating with histologically identified pathologies. Compared with the higher correlation levels reflecting axonal injury pathology in the normal rat mild TBI, the DTI and MTR metrics were more affected by the increased inflammation in the MVM rat mild TBI. Because MVM Wistar rats appear normal, there was a need to screen rats prior to TBI research to rule out the presence of ventriculomegaly, which may complicate the interpretation of imaging and IHC observations. PMID:26905805

Time course of clinical change following neurofeedback.

PubMed

Rance, Mariela; Walsh, Christopher; Sukhodolsky, Denis G; Pittman, Brian; Qiu, Maolin; Kichuk, Stephen A; Wasylink, Suzanne; Koller, William N; Bloch, Michael; Gruner, Patricia; Scheinost, Dustin; Pittenger, Christopher; Hampson, Michelle

2018-05-02

Neurofeedback - learning to modulate brain function through real-time monitoring of current brain state - is both a powerful method to perturb and probe brain function and an exciting potential clinical tool. For neurofeedback effects to be useful clinically, they must persist. Here we examine the time course of symptom change following neurofeedback in two clinical populations, combining data from two ongoing neurofeedback studies. This analysis reveals a shared pattern of symptom change, in which symptoms continue to improve for weeks after neurofeedback. This time course has several implications for future neurofeedback studies. Most neurofeedback studies are not designed to test an intervention with this temporal pattern of response. We recommend that new studies incorporate regular follow-up of subjects for weeks or months after the intervention to ensure that the time point of greatest effect is sampled. Furthermore, this time course of continuing clinical change has implications for crossover designs, which may attribute long-term, ongoing effects of real neurofeedback to the control intervention that follows. Finally, interleaving neurofeedback sessions with assessments and examining when clinical improvement peaks may not be an appropriate approach to determine the optimal number of sessions for an application. Copyright © 2018 Elsevier Inc. All rights reserved.

The role of the cerebral capillaries in acute ischemic stroke: the extended penumbra model.

PubMed

Østergaard, Leif; Jespersen, Sune Nørhøj; Mouridsen, Kim; Mikkelsen, Irene Klærke; Jonsdottír, Kristjana Ýr; Tietze, Anna; Blicher, Jakob Udby; Aamand, Rasmus; Hjort, Niels; Iversen, Nina Kerting; Cai, Changsi; Hougaard, Kristina Dupont; Simonsen, Claus Z; Von Weitzel-Mudersbach, Paul; Modrau, Boris; Nagenthiraja, Kartheeban; Riisgaard Ribe, Lars; Hansen, Mikkel Bo; Bekke, Susanne Lise; Dahlman, Martin Gervais; Puig, Josep; Pedraza, Salvador; Serena, Joaquín; Cho, Tae-Hee; Siemonsen, Susanne; Thomalla, Götz; Fiehler, Jens; Nighoghossian, Norbert; Andersen, Grethe

2013-05-01

The pathophysiology of cerebral ischemia is traditionally understood in relation to reductions in cerebral blood flow (CBF). However, a recent reanalysis of the flow-diffusion equation shows that increased capillary transit time heterogeneity (CTTH) can reduce the oxygen extraction efficacy in brain tissue for a given CBF. Changes in capillary morphology are typical of conditions predisposing to stroke and of experimental ischemia. Changes in capillary flow patterns have been observed by direct microscopy in animal models of ischemia and by indirect methods in humans stroke, but their metabolic significance remain unclear. We modeled the effects of progressive increases in CTTH on the way in which brain tissue can secure sufficient oxygen to meet its metabolic needs. Our analysis predicts that as CTTH increases, CBF responses to functional activation and to vasodilators must be suppressed to maintain sufficient tissue oxygenation. Reductions in CBF, increases in CTTH, and combinations thereof can seemingly trigger a critical lack of oxygen in brain tissue, and the restoration of capillary perfusion patterns therefore appears to be crucial for the restoration of the tissue oxygenation after ischemic episodes. In this review, we discuss the possible implications of these findings for the prevention, diagnosis, and treatment of acute stroke.

Microglia During Development and Aging

PubMed Central

Harry, G. Jean

2013-01-01

Microglia are critical nervous system-specific cells influencing brain development, maintenance of the neural environment, response to injury, and repair. They contribute to neuronal proliferation and differentiation, pruning of dying neurons, synaptic remodeling and clearance of debris and aberrant proteins. Colonization of the brain occurs during gestation with an expansion following birth with localization stimulated by programmed neuronal death, synaptic pruning, andaxonal degeneration. Changes inmicroglia phenotype relate to cellular processes including specific neurotransmitter, pattern recognition, or immune-related receptor activation. Upon activation, microglia cells have the capacity to release a number of substances, e.g., cytokines, chemokines, nitric oxide, and reactive oxygen species, which could be detrimental or beneficial to the surrounding cells. With aging, microglia shift their morphology and may display diminished capacity for normal functions related to migration, clearance, and the ability to shift from a pro-inflammatory to an anti-inflammatory state to regulate injury and repair. This shift in microgliapotentially contributes to increased susceptibility and neurodegeneration as a function of age. In the current review, information is provided on the colonization of the brain by microglia, the expression of various pattern recognition receptors to regulate migration and phagocytosis, and the shift in related functions that occur in normal aging. PMID:23644076

Shadows of Music-Language Interaction on Low Frequency Brain Oscillatory Patterns

ERIC Educational Resources Information Center

Carrus, Elisa; Koelsch, Stefan; Bhattacharya, Joydeep

2011-01-01

Electrophysiological studies investigating similarities between music and language perception have relied exclusively on the signal averaging technique, which does not adequately represent oscillatory aspects of electrical brain activity that are relevant for higher cognition. The current study investigated the patterns of brain oscillations…

Food portion size and energy density evoke different patterns of brain activation in children12

PubMed Central

Fearnbach, S Nicole; Wilson, Stephen J; Fisher, Jennifer O; Savage, Jennifer S; Rolls, Barbara J; Keller, Kathleen L

2017-01-01

Background: Large portions of food promote intake, but the mechanisms that drive this effect are unclear. Previous neuroimaging studies have identified the brain-reward and decision-making systems that are involved in the response to the energy density (ED) (kilocalories per gram) of foods, but few studies have examined the brain response to the food portion size (PS). Objective: We used functional MRI (fMRI) to determine the brain response to food images that differed in PSs (large and small) and ED (high and low). Design: Block-design fMRI was used to assess the blood oxygen level–dependent (BOLD) response to images in 36 children (7–10 y old; girls: 50%), which was tested after a 2-h fast. Pre-fMRI fullness and liking were rated on visual analog scales. A whole-brain cluster-corrected analysis was used to compare BOLD activation for main effects of the PS, ED, and their interaction. Secondary analyses were used to associate BOLD contrast values with appetitive traits and laboratory intake from meals for which the portions of all foods were increased. Results: Compared with small-PS cues, large-PS cues were associated with decreased activation in the inferior frontal gyrus (P < 0.01). Compared with low-ED cues, high-ED cues were associated with increased activation in multiple regions (e.g., in the caudate, cingulate, and precentral gyrus) and decreased activation in the insula and superior temporal gyrus (P < 0.01 for all). A PS × ED interaction was shown in the superior temporal gyrus (P < 0.01). BOLD contrast values for high-ED cues compared with low-ED cues in the insula, declive, and precentral gyrus were negatively related to appetitive traits (P < 0.05). There were no associations between the brain response to the PS and either appetitive traits or intake. Conclusions: Cues regarding food PS may be processed in the lateral prefrontal cortex, which is a region that is implicated in cognitive control, whereas ED activates multiple areas involved in sensory and reward processing. Possible implications include the development of interventions that target decision-making and reward systems differently to moderate overeating. PMID:27881393

Stress response in postpartum women with and without obsessive–compulsive symptoms: an fMRI study

PubMed Central

Lord, Catherine; Steiner, Meir; Soares, Claudio N.; Carew, Caitlin L.; Hall, Geoffrey B.

2012-01-01

Background During the postpartum period, some women might be under a considerable amount of stress and at increased risk for onset or exacerbation of obsessive–compulsive disorder (OCD). Little is known about the stress response correlates during the postpartum period and in patients with OCD. This study aimed to examine the cerebral, psychologic and endocrine correlates of the stress response in patients with OCD and during the postpartum period. Methods Women with postpartum OCD, healthy postpartum women and healthy mothers past the postpartum period underwent functional magnetic resonance imaging while facing a reliable psychosocial stressor (the Montreal Imaging Stress Task). Stress-related psychologic and endocrine responses (i.e., cortisol) were obtained. Results We enrolled 12 women with postpartum OCD, 16 healthy postpartum women and 11 healthy mothers past the postpartum period in our study. Compared with healthy postpartum counterparts, postpartum women with OCD had a heightened self-reported and endocrine stress response associated with a distinct brain activation pattern in response to psychosocial stress involving the orbitofrontal and temporal cortices. Moreover, compared with mothers assessed in a period of time beyond the postpartum period, healthy postpartum women did not differ in psychologic and cortisol response to stress, but recruited different brain regions, such as the dorsolateral pre-frontal cortex and the anterior cingulate cortex, during exposure to stress. Limitations Potential confounding factors, such as medication use, breastfeeding, parity and personality factors, may have modulated the stress-related endocrine response and could not be assessed in this study. Conclusion Obsessive–compulsive disorder and the postpartum period differentially influence the brain circuitry underlying psychosocial stress as well as the psychologic and endocrine responses. PMID:22122779

Are age and sex differences in brain oxytocin receptors related to maternal and infanticidal behavior in naïve mice?

PubMed

Olazábal, Daniel E; Alsina-Llanes, Marcela

2016-01-01

This article is part of a Special Issue "Parental Care". There is significant variability in the behavioral responses displayed by naïve young and adult mice when first exposed to pups. This variability has been associated with differences in the expression of oxytocin receptors (OXTRs) in the brain in several species. Experiment I investigated the behavioral responses of juvenile, adolescent, and adult CB57BL/6 males and females when first exposed to pups. We found an age increase in maternal females (11% of juveniles, 20% of adolescents, and 50% of young adults), and infanticidal males (0% of juveniles, 30% of adolescents, 44.5% of young adults, and 100% of older adults). Experiment II investigated OXTR density in the brain of juvenile and adult mice. Our results revealed an age decline in the density of OXTR in several brain regions, including the lateral septum, cingulated and posterior paraventricular thalamic nucleus in both males and females. Adult females had higher OXTR density in the ventromedial nucleus/postero-ventral hypothalamus (VMH) and the accessory olfactory bulb (AOB), but lower density in the ventral region of the lateral septum (LSv) than juveniles. Males had lower OXTR density in the anterior olfactory area (AOA) compared to juveniles. No age or sex differences were found in the medial preoptic area, and amygdaloid nuclei, among other brain regions. This study suggests that 1) maturation of parental and infanticidal behavioral responses is not reached until adulthood; 2) the pattern of development of OXTR in the mouse brain is unique, region specific, and differs from that observed in other rodents; 3) either up or down regulation of OXTR in a few brain regions (VMH/AOB/LSv/AOA) might contribute to age or sex differences in parental or infanticidal behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Morphological processing in a second language: behavioral and event-related brain potential evidence for storage and decomposition.

PubMed

Hahne, Anja; Mueller, Jutta L; Clahsen, Harald

2006-01-01

This study reports the results of two behavioral and two event-related brain potential experiments examining the processing of inflected words in second-language (L2) learners with Russian as their native language. Two different subsystems of German inflection were studied, participial inflection and noun plurals. For participial forms, L2 learners were found to widely generalize the -t suffixation rule in a nonce-word elicitation task, and in the event-related brain potential experiment, they showed an anterior negativity followed by a P600-both results resembling previous findings from native speakers of German on the same materials. For plural formation, the L2 learners displayed different preference patterns for regular and irregular forms in an off-line plural judgment task. Regular and irregular plural forms also differed clearly with regard to their brain responses. Whereas overapplications of the -s plural rule produced a P600 component, overapplications of irregular patterns elicited an N400. In contrast to native speakers of German, however, the L2 learners did not show an anterior negativity for -s plural overapplications. Taken together, the results show clear dissociations between regular and irregular inflection for both morphological subsystems. We argue that the two processing routes posited by dual-mechanism models of inflection (lexical storage and morphological decomposition) are also employed by L2 learners.

Stress-induced activation of the immediate early gene Arc (activity-regulated cytoskeleton-associated protein) is restricted to telencephalic areas in the rat brain: relationship to c-fos mRNA.

PubMed

Ons, Sheila; Martí, Octavi; Armario, Antonio

2004-06-01

Arc is an effector immediate early gene whose expression is induced in situations of increased neuronal activity. However, there is no report on the influence of stress on Arc expression. Here, we compared the induction of both c-fos and Arc mRNAs in the brain of rats exposed to one of three different stressful situations: novel environment, forced swimming and immobilization. An absent or weak c-fos mRNA signal was observed in control rats, whereas those exposed to one of three stressors showed enhanced c-fos expression in a wide range of brain areas. Constitutive Arc expression was observed in some areas such as cortex, striatum, hippocampus, reticular thalamic nucleus and cerebellar cortex. In response to stressors, a strong induction of Arc was observed, but the pattern was different from that of c-fos. For instance, activation of Arc but not c-fos was observed in the nucleus accumbens after immobilization and in the hippocampus after novel environment. No Arc induction was observed in diencephalic and brainstem areas. The present data show that Arc has a neuroanatomically restricted pattern of induction in the brain after emotional stress. Telencephalic activation suggests that a more intense induction of synaptic plasticity is occurring in this area after exposure to emotional stressors.

Scale invariant rearrangement of resting state networks in the human brain under sustained stimulation.

PubMed

Tommasin, Silvia; Mascali, Daniele; Moraschi, Marta; Gili, Tommaso; Assan, Ibrahim Eid; Fratini, Michela; DiNuzzo, Mauro; Wise, Richard G; Mangia, Silvia; Macaluso, Emiliano; Giove, Federico

2018-06-14

Brain activity at rest is characterized by widely distributed and spatially specific patterns of synchronized low-frequency blood-oxygenation level-dependent (BOLD) fluctuations, which correspond to physiologically relevant brain networks. This network behaviour is known to persist also during task execution, yet the details underlying task-associated modulations of within- and between-network connectivity are largely unknown. In this study we exploited a multi-parametric and multi-scale approach to investigate how low-frequency fluctuations adapt to a sustained n-back working memory task. We found that the transition from the resting state to the task state involves a behaviourally relevant and scale-invariant modulation of synchronization patterns within both task-positive and default mode networks. Specifically, decreases of connectivity within networks are accompanied by increases of connectivity between networks. In spite of large and widespread changes of connectivity strength, the overall topology of brain networks is remarkably preserved. We show that these findings are strongly influenced by connectivity at rest, suggesting that the absolute change of connectivity (i.e., disregarding the baseline) may be not the most suitable metric to study dynamic modulations of functional connectivity. Our results indicate that a task can evoke scale-invariant, distributed changes of BOLD fluctuations, further confirming that low frequency BOLD oscillations show a specialized response and are tightly bound to task-evoked activation. Copyright © 2018. Published by Elsevier Inc.

How task demands shape brain responses to visual food cues.

PubMed

Pohl, Tanja Maria; Tempelmann, Claus; Noesselt, Toemme

2017-06-01

Several previous imaging studies have aimed at identifying the neural basis of visual food cue processing in humans. However, there is little consistency of the functional magnetic resonance imaging (fMRI) results across studies. Here, we tested the hypothesis that this variability across studies might - at least in part - be caused by the different tasks employed. In particular, we assessed directly the influence of task set on brain responses to food stimuli with fMRI using two tasks (colour vs. edibility judgement, between-subjects design). When participants judged colour, the left insula, the left inferior parietal lobule, occipital areas, the left orbitofrontal cortex and other frontal areas expressed enhanced fMRI responses to food relative to non-food pictures. However, when judging edibility, enhanced fMRI responses to food pictures were observed in the superior and middle frontal gyrus and in medial frontal areas including the pregenual anterior cingulate cortex and ventromedial prefrontal cortex. This pattern of results indicates that task sets can significantly alter the neural underpinnings of food cue processing. We propose that judging low-level visual stimulus characteristics - such as colour - triggers stimulus-related representations in the visual and even in gustatory cortex (insula), whereas discriminating abstract stimulus categories activates higher order representations in both the anterior cingulate and prefrontal cortex. Hum Brain Mapp 38:2897-2912, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Smoking modulates language lateralization in a sex-specific way.

PubMed

Hahn, Constanze; Pogun, Sakire; Güntürkün, Onur

2010-12-01

Smoking affects a widespread network of neuronal functions by altering the properties of acetylcholinergic transmission. Recent studies show that nicotine consumption affects ascending auditory pathways and alters auditory attention, particularly in men. Here we show that smoking affects language lateralization in a sex-specific way. We assessed brain asymmetries of 90 healthy, right-handed participants using a classic consonant-vowel syllable dichotic listening paradigm in a 2×3 experimental design with sex (male, female) and smoking status (non-smoker, light smoker, heavy smoker) as between-subject factors. Our results revealed that male smokers had a significantly less lateralized response pattern compared to the other groups due to a decreased response rate of their right ear. This finding suggests a group-specific impairment of the speech dominant left hemisphere. In addition, decreased overall response accuracy was observed in male smokers compared to the other experimental groups. Similar adverse effects of smoking were not detected in women. Further, a significant negative correlation was detected between the severity of nicotine dependency and response accuracy in male but not in female smokers. Taken together, these results show that smoking modulates functional brain lateralization significantly and in a sexually dimorphic manner. Given that some psychiatric disorders have been associated with altered brain asymmetries and increased smoking prevalence, nicotinergic effects need to be specifically investigated in this context in future studies. Copyright © 2010 Elsevier Ltd. All rights reserved.

Orientation selective deep brain stimulation

NASA Astrophysics Data System (ADS)

Lehto, Lauri J.; Slopsema, Julia P.; Johnson, Matthew D.; Shatillo, Artem; Teplitzky, Benjamin A.; Utecht, Lynn; Adriany, Gregor; Mangia, Silvia; Sierra, Alejandra; Low, Walter C.; Gröhn, Olli; Michaeli, Shalom

2017-02-01

Objective. Target selectivity of deep brain stimulation (DBS) therapy is critical, as the precise locus and pattern of the stimulation dictates the degree to which desired treatment responses are achieved and adverse side effects are avoided. There is a clear clinical need to improve DBS technology beyond currently available stimulation steering and shaping approaches. We introduce orientation selective neural stimulation as a concept to increase the specificity of target selection in DBS. Approach. This concept, which involves orienting the electric field along an axonal pathway, was tested in the corpus callosum of the rat brain by freely controlling the direction of the electric field on a plane using a three-electrode bundle, and monitoring the response of the neurons using functional magnetic resonance imaging (fMRI). Computational models were developed to further analyze axonal excitability for varied electric field orientation. Main results. Our results demonstrated that the strongest fMRI response was observed when the electric field was oriented parallel to the axons, while almost no response was detected with the perpendicular orientation of the electric field relative to the primary fiber tract. These results were confirmed by computational models of the experimental paradigm quantifying the activation of radially distributed axons while varying the primary direction of the electric field. Significance. The described strategies identify a new course for selective neuromodulation paradigms in DBS based on axonal fiber orientation.

Where Is the Beat? The Neural Correlates of Lexical Stress and Rhythmical Well-formedness in Auditory Story Comprehension.

PubMed

Kandylaki, Katerina D; Henrich, Karen; Nagels, Arne; Kircher, Tilo; Domahs, Ulrike; Schlesewsky, Matthias; Bornkessel-Schlesewsky, Ina; Wiese, Richard

2017-07-01

While listening to continuous speech, humans process beat information to correctly identify word boundaries. The beats of language are stress patterns that are created by combining lexical (word-specific) stress patterns and the rhythm of a specific language. Sometimes, the lexical stress pattern needs to be altered to obey the rhythm of the language. This study investigated the interplay of lexical stress patterns and rhythmical well-formedness in natural speech with fMRI. Previous electrophysiological studies on cases in which a regular lexical stress pattern may be altered to obtain rhythmical well-formedness showed that even subtle rhythmic deviations are detected by the brain if attention is directed toward prosody. Here, we present a new approach to this phenomenon by having participants listen to contextually rich stories in the absence of a task targeting the manipulation. For the interaction of lexical stress and rhythmical well-formedness, we found one suprathreshold cluster localized between the cerebellum and the brain stem. For the main effect of lexical stress, we found higher BOLD responses to the retained lexical stress pattern in the bilateral SMA, bilateral postcentral gyrus, bilateral middle fontal gyrus, bilateral inferior and right superior parietal lobule, and right precuneus. These results support the view that lexical stress is processed as part of a sensorimotor network of speech comprehension. Moreover, our results connect beat processing in language to domain-independent timing perception.

Controlled Low-Pressure Blast-Wave Exposure Causes Distinct Behavioral and Morphological Responses Modelling Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Comorbid Mild Traumatic Brain Injury-Post-Traumatic Stress Disorder.

PubMed

Zuckerman, Amitai; Ram, Omri; Ifergane, Gal; Matar, Michael A; Sagi, Ram; Ostfeld, Ishay; Hoffman, Jay R; Kaplan, Zeev; Sadot, Oren; Cohen, Hagit

2017-01-01

The intense focus in the clinical literature on the mental and neurocognitive sequelae of explosive blast-wave exposure, especially when comorbid with post-traumatic stress-related disorders (PTSD) is justified, and warrants the design of translationally valid animal studies to provide valid complementary basic data. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast-wave produced by exploding a thin copper wire. By combining cognitive-behavioral paradigms and ex vivo brain MRI to assess mild traumatic brain injury (mTBI) phenotype with a validated behavioral model for PTSD, complemented by morphological assessments, this study sought to examine our ability to evaluate the biobehavioral effects of low-intensity blast overpressure on rats, in a translationally valid manner. There were no significant differences between blast- and sham-exposed rats on motor coordination and strength, or sensory function. Whereas most male rats exposed to the blast-wave displayed normal behavioral and cognitive responses, 23.6% of the rats displayed a significant retardation of spatial learning acquisition, fulfilling criteria for mTBI-like responses. In addition, 5.4% of the blast-exposed animals displayed an extreme response in the behavioral tasks used to define PTSD-like criteria, whereas 10.9% of the rats developed both long-lasting and progressively worsening behavioral and cognitive "symptoms," suggesting comorbid PTSD-mTBI-like behavioral and cognitive response patterns. Neither group displayed changes on MRI. Exposure to experimental blast-wave elicited distinct behavioral and morphological responses modelling mTBI-like, PTSD-like, and comorbid mTBI-PTSD-like responses. This experimental animal model can be a useful tool for elucidating neurobiological mechanisms underlying the effects of blast-wave-induced mTBI and PTSD and comorbid mTBI-PTSD.

Differential Recruitment of Brain Regions During Response Inhibition in Children Prenatally Exposed to Alcohol.

PubMed

Kodali, Vikas N; Jacobson, Joseph L; Lindinger, Nadine M; Dodge, Neil C; Molteno, Christopher D; Meintjes, Ernesta M; Jacobson, Sandra W

2017-02-01

Response inhibition is a distinct aspect of executive function that is frequently impaired in children with fetal alcohol spectrum disorders (FASD). We used a Go/NoGo (GNG) task in a functional MRI protocol to investigate differential activation of brain regions in the response inhibition network in children diagnosed with full or partial fetal alcohol syndrome (FAS/PFAS), compared with healthy controls. A rapid, event-related task with 120 Go and 60 NoGo trials was used to study children aged 8 to 12 years-8 with FAS/PFAS, 17 controls. Letters were projected sequentially, with Go and NoGo trials randomly interspersed across the task. BOLD signal in the whole brain was contrasted for the correct NoGo minus correct Go trials between the FAS/PFAS and control groups. Compared to the FAS/PFAS group, controls showed greater activation of the inferior frontal and anterior cingulate network linked to response inhibition in typically developing children. By contrast, the FAS/PFAS group showed greater BOLD response in dorsolateral prefrontal cortex and other middle prefrontal regions, suggesting compensation for inefficient function of pathways that normally mediate inhibitory processing. All group differences were significant after control for potential confounding variables. None of the effects of prenatal alcohol exposure on activation of the regions associated with response inhibition were attributable to the effects of this exposure on IQ. This is the first FASD GNG study in which all participants in the exposed group met criteria for a diagnosis of full FAS or PFAS. Although FASD is frequently comorbid with attention deficit hyperactivity disorder, the pattern of brain activation seen in these disorders differs, suggesting that different neural pathways mediate response inhibition in FASD and that different interventions for FASD are, therefore, warranted. Copyright © 2017 by the Research Society on Alcoholism.

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.

Brain coordination dynamics: True and false faces of phase synchrony and metastability

PubMed Central

Tognoli, Emmanuelle; Kelso, J.A. Scott

2009-01-01

Understanding the coordination of multiple parts in a complex system such as the brain is a fundamental challenge. We present a theoretical model of cortical coordination dynamics that shows how brain areas may cooperate (integration) and at the same time retain their functional specificity (segregation). This model expresses a range of desirable properties that the brain is known to exhibit, including self-organization, multi-functionality, metastability and switching. Empirically, the model motivates a thorough investigation of collective phase relationships among brain oscillations in neurophysiological data. The most serious obstacle to interpreting coupled oscillations as genuine evidence of inter-areal coordination in the brain stems from volume conduction of electrical fields. Spurious coupling due to volume conduction gives rise to zero-lag (inphase) and antiphase synchronization whose magnitude and persistence obscure the subtle expression of real synchrony. Through forward modeling and the help of a novel colorimetric method, we show how true synchronization can be deciphered from continuous EEG patterns. Developing empirical efforts along the lines of continuous EEG analysis constitutes a major response to the challenge of understanding how different brain areas work together. Key predictions of cortical coordination dynamics can now be tested thereby revealing the essential modus operandi of the intact living brain. PMID:18938209

Précis of The brain and emotion.

PubMed

Rolls, E T

2000-04-01

The topics treated in The brain and emotion include the definition, nature, and functions of emotion (Ch. 3); the neural bases of emotion (Ch. 4); reward, punishment, and emotion in brain design (Ch. 10); a theory of consciousness and its application to understanding emotion and pleasure (Ch. 9); and neural networks and emotion-related learning (Appendix). The approach is that emotions can be considered as states elicited by reinforcers (rewards and punishers). This approach helps with understanding the functions of emotion, with classifying different emotions, and in understanding what information-processing systems in the brain are involved in emotion, and how they are involved. The hypothesis is developed that brains are designed around reward- and punishment-evaluation systems, because this is the way that genes can build a complex system that will produce appropriate but flexible behavior to increase fitness (Ch. 10). By specifying goals rather than particular behavioral patterns of responses, genes leave much more open the possible behavioral strategies that might be required to increase fitness. The importance of reward and punishment systems in brain design also provides a basis for understanding the brain mechanisms of motivation, as described in Chapters 2 for appetite and feeding, 5 for brain-stimulation reward, 6 for addiction, 7 for thirst, and 8 for sexual behavior.

Spatially Pooled Contrast Responses Predict Neural and Perceptual Similarity of Naturalistic Image Categories

PubMed Central

Groen, Iris I. A.; Ghebreab, Sennay; Lamme, Victor A. F.; Scholte, H. Steven

2012-01-01

The visual world is complex and continuously changing. Yet, our brain transforms patterns of light falling on our retina into a coherent percept within a few hundred milliseconds. Possibly, low-level neural responses already carry substantial information to facilitate rapid characterization of the visual input. Here, we computationally estimated low-level contrast responses to computer-generated naturalistic images, and tested whether spatial pooling of these responses could predict image similarity at the neural and behavioral level. Using EEG, we show that statistics derived from pooled responses explain a large amount of variance between single-image evoked potentials (ERPs) in individual subjects. Dissimilarity analysis on multi-electrode ERPs demonstrated that large differences between images in pooled response statistics are predictive of more dissimilar patterns of evoked activity, whereas images with little difference in statistics give rise to highly similar evoked activity patterns. In a separate behavioral experiment, images with large differences in statistics were judged as different categories, whereas images with little differences were confused. These findings suggest that statistics derived from low-level contrast responses can be extracted in early visual processing and can be relevant for rapid judgment of visual similarity. We compared our results with two other, well- known contrast statistics: Fourier power spectra and higher-order properties of contrast distributions (skewness and kurtosis). Interestingly, whereas these statistics allow for accurate image categorization, they do not predict ERP response patterns or behavioral categorization confusions. These converging computational, neural and behavioral results suggest that statistics of pooled contrast responses contain information that corresponds with perceived visual similarity in a rapid, low-level categorization task. PMID:23093921

Distributed Patterns of Reactivation Predict Vividness of Recollection.

PubMed

St-Laurent, Marie; Abdi, Hervé; Buchsbaum, Bradley R

2015-10-01

According to the principle of reactivation, memory retrieval evokes patterns of brain activity that resemble those instantiated when an event was first experienced. Intuitively, one would expect neural reactivation to contribute to recollection (i.e., the vivid impression of reliving past events), but evidence of a direct relationship between the subjective quality of recollection and multiregional reactivation of item-specific neural patterns is lacking. The current study assessed this relationship using fMRI to measure brain activity as participants viewed and mentally replayed a set of short videos. We used multivoxel pattern analysis to train a classifier to identify individual videos based on brain activity evoked during perception and tested how accurately the classifier could distinguish among videos during mental replay. Classification accuracy correlated positively with memory vividness, indicating that the specificity of multivariate brain patterns observed during memory retrieval was related to the subjective quality of a memory. In addition, we identified a set of brain regions whose univariate activity during retrieval predicted both memory vividness and the strength of the classifier's prediction irrespective of the particular video that was retrieved. Our results establish distributed patterns of neural reactivation as a valid and objective marker of the quality of recollection.

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

Does body mass play a role in the regulation of food intake?

PubMed

Speakman, John R; Stubbs, R James; Mercer, Julian G

2002-11-01

It is widely believed that body fatness (and hence total body mass) is regulated by a lipostatic feedback system. This system is suggested to involve at least one peripheral signalling compound, which signals to the brain the current size of body fat stores. In the brain the level of the signal is compared with a desirable target level, and food intake and energy expenditure are then regulated to effect changes in the size of body fat stores. There is considerable support for this theory at several different levels of investigation. Patterns of body-mass change in subjects forced into energy imbalance seem to demonstrate homeostasis, and long-term changes in body mass are minor compared with the potential changes that might result from energy imbalance. Molecular studies of signalling compounds have suggested a putative lipostatic signal (leptin) and a complex network of downstream processing events in the brain, polymorphisms of which lead to disruption of body-mass regulation. This network of neuropeptides provides a rich seam of potential pharmaceutical targets for the control of obesity. Despite this consistent explanation for the observed phenomena at several different levels of enquiry, there are alternative explanations. In the present paper we explore the possibility that the existence of lipostatic regulation of body fatness is an illusion generated by the links between body mass and energy expenditure and responses to energy imbalance that are independent of body mass. Using computer-based models of temporal patterns in energy balance we show that common patterns of change in body mass following perturbation can be adequately explained by this 'non-lipostatic' model. This model has some important implications for the interpretations that we place on the molecular events in the brain, and ultimately in the search for pharmaceutical agents for alleviation of obesity.

Brain activity and connectivity during poetry composition: Toward a multidimensional model of the creative process

PubMed Central

Liu, Siyuan; Erkkinen, Michael G.; Healey, Meghan L.; Xu, Yisheng; Swett, Katherine E.; Chow, Ho Ming

2015-01-01

Abstract Creativity, a multifaceted construct, can be studied in various ways, for example, investigating phases of the creative process, quality of the creative product, or the impact of expertise. Previous neuroimaging studies have assessed these individually. Believing that each of these interacting features must be examined simultaneously to develop a comprehensive understanding of creative behavior, we examined poetry composition, assessing process, product, and expertise in a single experiment. Distinct activation patterns were associated with generation and revision, two major phases of the creative process. Medial prefrontal cortex (MPFC) was active during both phases, yet responses in dorsolateral prefrontal and parietal executive systems (DLPFC/IPS) were phase‐dependent, indicating that while motivation remains unchanged, cognitive control is attenuated during generation and re‐engaged during revision. Experts showed significantly stronger deactivation of DLPFC/IPS during generation, suggesting that they may more effectively suspend cognitive control. Importantly however, similar overall patterns were observed in both groups, indicating the same cognitive resources are available to experts and novices alike. Quality of poetry, assessed by an independent panel, was associated with divergent connectivity patterns in experts and novices, centered upon MPFC (for technical facility) and DLPFC/IPS (for innovation), suggesting a mechanism by which experts produce higher quality poetry. Crucially, each of these three key features can be understood in the context of a single neurocognitive model characterized by dynamic interactions between medial prefrontal areas regulating motivation, dorsolateral prefrontal, and parietal areas regulating cognitive control and the association of these regions with language, sensorimotor, limbic, and subcortical areas distributed throughout the brain. Hum Brain Mapp 36:3351–3372, 2015. © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:26015271

Retronasal odor representations in the dorsal olfactory bulb of rats

PubMed Central

Gautam, Shree Hari; Verhagen, Justus V.

2012-01-01

Animals perceive their olfactory environment not only from odors originating in the external world (orthonasal route) but also from odors released in the oral cavity while eating food (retronasal route). Retronasal olfaction is crucial for the perception of food flavor in humans. However, little is known about the retronasal stimulus coding in the brain. The most basic question is if and how route affects the odor representations at the level of the olfactory bulb (OB), where odor quality codes originate. We used optical calcium imaging of presynaptic dorsal OB responses to odorants in anesthetized rats to ask whether the rat OB could be activated retronasally, and how these responses compare to orthonasal responses under similar conditions. We further investigated the effects of specific odorant properties on orthoversus retronasal response patterns. We found that at a physiologically relevant flow rate retronasal odorants can effectively reach the olfactory receptor neurons, eliciting glomerular response patterns that grossly overlap with those of orthonasal responses, but differ from the orthonasal patterns in the response amplitude and temporal dynamics. Interestingly, such differences correlated well with specific odorant properties. Less volatile odorants yielded relatively smaller responses retronasally, but volatility did not affect relative temporal profiles. More polar odorants responded with relatively longer onset latency and time to peak retronasally, but polarity did not affect relative response magnitudes. These data provide insight into the early stages of retronasal stimulus coding and establish relationships between ortho- and retronasal odor representations in the rat OB. PMID:22674270

Abnormal early dynamic individual patterns of functional networks in low gamma band for depression recognition.

PubMed

Bi, Kun; Chattun, Mahammad Ridwan; Liu, Xiaoxue; Wang, Qiang; Tian, Shui; Zhang, Siqi; Lu, Qing; Yao, Zhijian

2018-06-13

The functional networks are associated with emotional processing in depression. The mapping of dynamic spatio-temporal brain networks is used to explore individual performance during early negative emotional processing. However, the dysfunctions of functional networks in low gamma band and their discriminative potentialities during early period of emotional face processing remain to be explored. Functional brain networks were constructed from the MEG recordings of 54 depressed patients and 54 controls in low gamma band (30-48 Hz). Dynamic connectivity regression (DCR) algorithm analyzed the individual change points of time series in response to emotional stimuli and constructed individualized spatio-temporal patterns. The nodal characteristics of patterns were calculated and fed into support vector machine (SVM). Performance of the classification algorithm in low gamma band was validated by dynamic topological characteristics of individual patterns in comparison to alpha and beta band. The best discrimination accuracy of individual spatio-temporal patterns was 91.01% in low gamma band. Individual temporal patterns had better results compared to group-averaged temporal patterns in all bands. The most important discriminative networks included affective network (AN) and fronto-parietal network (FPN) in low gamma band. The sample size is relatively small. High gamma band was not considered. The abnormal dynamic functional networks in low gamma band during early emotion processing enabled depression recognition. The individual information processing is crucial in the discovery of abnormal spatio-temporal patterns in depression during early negative emotional processing. Individual spatio-temporal patterns may reflect the real dynamic function of subjects while group-averaged data may neglect some individual information. Copyright © 2018. Published by Elsevier B.V.

Information spreading by a combination of MEG source estimation and multivariate pattern classification.

PubMed

Sato, Masashi; Yamashita, Okito; Sato, Masa-Aki; Miyawaki, Yoichi

2018-01-01

To understand information representation in human brain activity, it is important to investigate its fine spatial patterns at high temporal resolution. One possible approach is to use source estimation of magnetoencephalography (MEG) signals. Previous studies have mainly quantified accuracy of this technique according to positional deviations and dispersion of estimated sources, but it remains unclear how accurately MEG source estimation restores information content represented by spatial patterns of brain activity. In this study, using simulated MEG signals representing artificial experimental conditions, we performed MEG source estimation and multivariate pattern analysis to examine whether MEG source estimation can restore information content represented by patterns of cortical current in source brain areas. Classification analysis revealed that the corresponding artificial experimental conditions were predicted accurately from patterns of cortical current estimated in the source brain areas. However, accurate predictions were also possible from brain areas whose original sources were not defined. Searchlight decoding further revealed that this unexpected prediction was possible across wide brain areas beyond the original source locations, indicating that information contained in the original sources can spread through MEG source estimation. This phenomenon of "information spreading" may easily lead to false-positive interpretations when MEG source estimation and classification analysis are combined to identify brain areas that represent target information. Real MEG data analyses also showed that presented stimuli were able to be predicted in the higher visual cortex at the same latency as in the primary visual cortex, also suggesting that information spreading took place. These results indicate that careful inspection is necessary to avoid false-positive interpretations when MEG source estimation and multivariate pattern analysis are combined.

Information spreading by a combination of MEG source estimation and multivariate pattern classification

PubMed Central

Sato, Masashi; Yamashita, Okito; Sato, Masa-aki

2018-01-01

To understand information representation in human brain activity, it is important to investigate its fine spatial patterns at high temporal resolution. One possible approach is to use source estimation of magnetoencephalography (MEG) signals. Previous studies have mainly quantified accuracy of this technique according to positional deviations and dispersion of estimated sources, but it remains unclear how accurately MEG source estimation restores information content represented by spatial patterns of brain activity. In this study, using simulated MEG signals representing artificial experimental conditions, we performed MEG source estimation and multivariate pattern analysis to examine whether MEG source estimation can restore information content represented by patterns of cortical current in source brain areas. Classification analysis revealed that the corresponding artificial experimental conditions were predicted accurately from patterns of cortical current estimated in the source brain areas. However, accurate predictions were also possible from brain areas whose original sources were not defined. Searchlight decoding further revealed that this unexpected prediction was possible across wide brain areas beyond the original source locations, indicating that information contained in the original sources can spread through MEG source estimation. This phenomenon of “information spreading” may easily lead to false-positive interpretations when MEG source estimation and classification analysis are combined to identify brain areas that represent target information. Real MEG data analyses also showed that presented stimuli were able to be predicted in the higher visual cortex at the same latency as in the primary visual cortex, also suggesting that information spreading took place. These results indicate that careful inspection is necessary to avoid false-positive interpretations when MEG source estimation and multivariate pattern analysis are combined. PMID:29912968

The clinical outcomes of deep gray matter injury in children with cerebral palsy in relation with brain magnetic resonance imaging.

PubMed

Choi, Ja Young; Choi, Yoon Seong; Rha, Dong-Wook; Park, Eun Sook

2016-08-01

In the present study we investigated the nature and extent of clinical outcomes using various classifications and analyzed the relationship between brain magnetic resonance imaging (MRI) findings and the extent of clinical outcomes in children with cerebral palsy (CP) with deep gray matter injury. The deep gray matter injuries of 69 children were classified into hypoxic ischemic encephalopathy (HIE) and kernicterus patterns. HIE patterns were divided into four groups (I-IV) based on severity. Functional classification was investigated using the gross motor function classification system-expanded and revised, manual ability classification system, communication function classification system, and tests of cognitive function, and other associated problems. The severity of HIE pattern on brain MRI was strongly correlated with the severity of clinical outcomes in these various domains. Children with a kernicterus pattern showed a wide range of clinical outcomes in these areas. Children with severe HIE are at high risk of intellectual disability (ID) or epilepsy and children with a kernicterus pattern are at risk of hearing impairment and/or ID. Grading severity of HIE pattern on brain MRI is useful for predicting overall outcomes. The clinical outcomes of children with a kernicterus pattern range widely from mild to severe. Delineation of the clinical outcomes of children with deep gray matter injury, which are a common abnormal brain MRI finding in children with CP, is necessary. The present study provides clinical outcomes for various domains in children with deep gray matter injury on brain MRI. The deep gray matter injuries were divided into two major groups; HIE and kernicterus patterns. Our study showed that severity of HIE pattern on brain MRI was strongly associated with the severity of impairments in gross motor function, manual ability, communication function, and cognition. These findings suggest that severity of HIE pattern can be useful for predicting the severity of impairments. Conversely, children with a kernicterus pattern showed a wide range of clinical outcomes in various domains. Children with severe HIE pattern are at high risk of ID or epilepsy and children with kernicterus pattern are at risk of hearing impairment or ID. The strength of our study was the assessment of clinical outcomes after 3 years of age using standardized classification systems in various domains in children with deep gray matter injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

A comprehensive analysis on preservation patterns of gene co-expression networks during Alzheimer's disease progression.

PubMed

Ray, Sumanta; Hossain, Sk Md Mosaddek; Khatun, Lutfunnesa; Mukhopadhyay, Anirban

2017-12-20

Alzheimer's disease (AD) is a chronic neuro-degenerative disruption of the brain which involves in large scale transcriptomic variation. The disease does not impact every regions of the brain at the same time, instead it progresses slowly involving somewhat sequential interaction with different regions. Analysis of the expression patterns of the genes in different regions of the brain influenced in AD surely contribute for a enhanced comprehension of AD pathogenesis and shed light on the early characterization of the disease. Here, we have proposed a framework to identify perturbation and preservation characteristics of gene expression patterns across six distinct regions of the brain ("EC", "HIP", "PC", "MTG", "SFG", and "VCX") affected in AD. Co-expression modules were discovered considering a couple of regions at once. These are then analyzed to know the preservation and perturbation characteristics. Different module preservation statistics and a rank aggregation mechanism have been adopted to detect the changes of expression patterns across brain regions. Gene ontology (GO) and pathway based analysis were also carried out to know the biological meaning of preserved and perturbed modules. In this article, we have extensively studied the preservation patterns of co-expressed modules in six distinct brain regions affected in AD. Some modules are emerged as the most preserved while some others are detected as perturbed between a pair of brain regions. Further investigation on the topological properties of preserved and non-preserved modules reveals a substantial association amongst "betweenness centrality" and "degree" of the involved genes. Our findings may render a deeper realization of the preservation characteristics of gene expression patterns in discrete brain regions affected by AD.

Whole Brain Magnetic Resonance Spectroscopic Determinants of Functional Outcomes in Pediatric Moderate/Severe Traumatic Brain Injury.

PubMed

Babikian, Talin; Alger, Jeffry R; Ellis-Blied, Monica U; Giza, Christopher C; Dennis, Emily; Olsen, Alexander; Mink, Richard; Babbitt, Christopher; Johnson, Jeff; Thompson, Paul M; Asarnow, Robert F

2018-05-18

Diffuse axonal injury contributes to the long-term functional morbidity observed after pediatric moderate/severe traumatic brain injury (msTBI). Whole-brain proton magnetic resonance echo-planar spectroscopic imaging was used to measure the neurometabolite levels in the brain to delineate the course of disruption/repair during the first year post-msTBI. The association between metabolite biomarkers and functional measures (cognitive functioning and corpus callosum [CC] function assessed by interhemispheric transfer time [IHTT] using an event related potential paradigm) was also explored. Pediatric patients with msTBI underwent assessments at two times (post-acutely at a mean of three months post-injury, n = 31, and chronically at a mean of 16 months post-injury, n = 24). Healthy controls also underwent two evaluations, approximately 12 months apart. Post-acutely, in patients with msTBI, there were elevations in choline (Cho; marker for inflammation and/or altered membrane metabolism) in all four brain lobes and the CC and decreases in N-acetylaspartate (NAA; marker for neuronal and axonal integrity) in the CC compared with controls, all of which normalized by the chronic time point. Subgroups of TBI showed variable patterns chronically. Patients with slow IHTT had lower lobar Cho chronically than those with normal IHTT; they also did not show normalization in CC NAA whereas those with normal IHTT showed significantly higher levels of CC NAA relative to controls. In the normal IHTT group only, chronic CC Cho and NAA together explained 70% of the variance in long-term cognitive functioning. MR based whole brain metabolic evaluations show different patterns of neurochemistry after msTBI in two subgroups with different outcomes. There is a dynamic relationship between prolonged inflammatory responses to brain damage, reparative processes/remyelination, and subsequent neurobehavioral outcomes. Multimodal studies allow us to test hypotheses about degenerative and reparative processes in patient groups that have divergent functional outcome, with the ultimate goal of developing targeted therapeutic agents.

Disrupting the blood-brain barrier by focused ultrasound induces sterile inflammation.

PubMed

Kovacs, Zsofia I; Kim, Saejeong; Jikaria, Neekita; Qureshi, Farhan; Milo, Blerta; Lewis, Bobbi K; Bresler, Michele; Burks, Scott R; Frank, Joseph A

2017-01-03

MRI-guided pulsed focused ultrasound (pFUS) combined with systemic infusion of ultrasound contrast agent microbubbles (MB) causes localized blood-brain barrier (BBB) disruption that is currently being advocated for increasing drug or gene delivery in neurological diseases. The mechanical acoustic cavitation effects of opening the BBB by low-intensity pFUS+MB, as evidenced by contrast-enhanced MRI, resulted in an immediate damage-associated molecular pattern (DAMP) response including elevations in heat-shock protein 70, IL-1, IL-18, and TNFα indicative of a sterile inflammatory response (SIR) in the parenchyma. Concurrent with DAMP presentation, significant elevations in proinflammatory, antiinflammatory, and trophic factors along with neurotrophic and neurogenesis factors were detected; these elevations lasted 24 h. Transcriptomic analysis of sonicated brain supported the proteomic findings and indicated that the SIR was facilitated through the induction of the NFκB pathway. Histological evaluation demonstrated increased albumin in the parenchyma that cleared by 24 h along with TUNEL + neurons, activated astrocytes, microglia, and increased cell adhesion molecules in the vasculature. Infusion of fluorescent beads 3 d before pFUS+MB revealed the infiltration of CD68 + macrophages at 6 d postsonication, as is consistent with an innate immune response. pFUS+MB is being considered as part of a noninvasive adjuvant treatment for malignancy or neurodegenerative diseases. These results demonstrate that pFUS+MB induces an SIR compatible with ischemia or mild traumatic brain injury. Further investigation will be required before this approach can be widely implemented in clinical trials.

A review of group ICA for fMRI data and ICA for joint inference of imaging, genetic, and ERP data

PubMed Central

Calhoun, Vince D.; Liu, Jingyu; Adalı, Tülay

2009-01-01

Independent component analysis (ICA) has become an increasingly utilized approach for analyzing brain imaging data. In contrast to the widely used general linear model (GLM) that requires the user to parameterize the data (e.g. the brain's response to stimuli), ICA, by relying upon a general assumption of independence, allows the user to be agnostic regarding the exact form of the response. In addition, ICA is intrinsically a multivariate approach, and hence each component provides a grouping of brain activity into regions that share the same response pattern thus providing a natural measure of functional connectivity. There are a wide variety of ICA approaches that have been proposed, in this paper we focus upon two distinct methods. The first part of this paper reviews the use of ICA for making group inferences from fMRI data. We provide an overview of current approaches for utilizing ICA to make group inferences with a focus upon the group ICA approach implemented in the GIFT software. In the next part of this paper, we provide an overview of the use of ICA to combine or fuse multimodal data. ICA has proven particularly useful for data fusion of multiple tasks or data modalities such as single nucleotide polymorphism (SNP) data or event-related potentials. As demonstrated by a number of examples in this paper, ICA is a powerful and versatile data-driven approach for studying the brain. PMID:19059344

A review of group ICA for fMRI data and ICA for joint inference of imaging, genetic, and ERP data.

PubMed

Calhoun, Vince D; Liu, Jingyu; Adali, Tülay

2009-03-01

Independent component analysis (ICA) has become an increasingly utilized approach for analyzing brain imaging data. In contrast to the widely used general linear model (GLM) that requires the user to parameterize the data (e.g. the brain's response to stimuli), ICA, by relying upon a general assumption of independence, allows the user to be agnostic regarding the exact form of the response. In addition, ICA is intrinsically a multivariate approach, and hence each component provides a grouping of brain activity into regions that share the same response pattern thus providing a natural measure of functional connectivity. There are a wide variety of ICA approaches that have been proposed, in this paper we focus upon two distinct methods. The first part of this paper reviews the use of ICA for making group inferences from fMRI data. We provide an overview of current approaches for utilizing ICA to make group inferences with a focus upon the group ICA approach implemented in the GIFT software. In the next part of this paper, we provide an overview of the use of ICA to combine or fuse multimodal data. ICA has proven particularly useful for data fusion of multiple tasks or data modalities such as single nucleotide polymorphism (SNP) data or event-related potentials. As demonstrated by a number of examples in this paper, ICA is a powerful and versatile data-driven approach for studying the brain.

Effects of Weightlessness on Vestibular Development of Quail

NASA Technical Reports Server (NTRS)

Fritzsch, Bernd; Bruce, Laura L.

1997-01-01

The lack of gravity is known to alter vestibular responses in developing and adult vertebrates. One cause of these altered responses may be changes in the connections between the vestibular receptor and the brain. Therefore we propose to investigate the effects of gravity on the formations of connections between the gravity receptors of the ear and the brain in developing quail incubated in space beginning at an age before these connections are established (incubation day three) until near the time of hatching, when they are to some extent functional. This investigation will make use of a novel technique, the diffusion of a lipophilic dye, DiI, in fixed tissue. This technique can thus be used to analyze the connections in specimens fixed in orbit, thus eliminating changes due to the earth's gravity. The evaluation of the data will enable us to detect gross deviations from normal patterns as well as detailed quantitative deviations.

Somatosensory responses in a human motor cortex

PubMed Central

Donoghue, John P.; Hochberg, Leigh R.

2013-01-01

Somatic sensory signals provide a major source of feedback to motor cortex. Changes in somatosensory systems after stroke or injury could profoundly influence brain computer interfaces (BCI) being developed to create new output signals from motor cortex activity patterns. We had the unique opportunity to study the responses of hand/arm area neurons in primary motor cortex to passive joint manipulation in a person with a long-standing brain stem stroke but intact sensory pathways. Neurons responded to passive manipulation of the contralateral shoulder, elbow, or wrist as predicted from prior studies of intact primates. Thus fundamental properties and organization were preserved despite arm/hand paralysis and damage to cortical outputs. The same neurons were engaged by attempted arm actions. These results indicate that intact sensory pathways retain the potential to influence primary motor cortex firing rates years after cortical outputs are interrupted and may contribute to online decoding of motor intentions for BCI applications. PMID:23343902

High frequency oscillations in brain hemodynamic response

NASA Astrophysics Data System (ADS)

Akin, Ata; Bolay, Hayrunnisa

2007-07-01

Tight autoregulation of vessel tone guarantees proper delivery of nutrients to the tissues. This regulation is maintained at a more delicate level in the brain since any decrease in the supply of glucose and oxygen to neuronal tissues might lead to unrecoverable injury. Functional near infrared spectroscopy has been proposed as a new tool to monitor the cerebrovascular response during cognitive activity. We have observed that during a Stroop task three distinct oscillatory patterns govern the control of the cerebrovascular reactivity: very low frequency (0.02-0.05 Hz), low frequency (0.08-0.12 Hz) and high frequency (0.12-0.18 Hz). High frequency oscillations have been shown to be related to stress level of the subjects. Our findings indicate that as the stress level is increased so does the energy of the high frequency component indicating a higher stimulation from the autonomic nervous system.

Neuroinvasion and Inflammation in Viral Central Nervous System Infections

PubMed Central

Schroten, Horst

2016-01-01

Neurotropic viruses can cause devastating central nervous system (CNS) infections, especially in young children and the elderly. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) have been described as relevant sites of entry for specific viruses as well as for leukocytes, which are recruited during the proinflammatory response in the course of CNS infection. In this review, we illustrate examples of established brain barrier models, in which the specific reaction patterns of different viral families can be analyzed. Furthermore, we highlight the pathogen specific array of cytokines and chemokines involved in immunological responses in viral CNS infections. We discuss in detail the link between specific cytokines and chemokines and leukocyte migration profiles. The thorough understanding of the complex and interrelated inflammatory mechanisms as well as identifying universal mediators promoting CNS inflammation is essential for the development of new diagnostic and treatment strategies. PMID:27313404

Remembering what could have happened: Neural correlates of episodic counterfactual thinking

PubMed Central

De Brigard, F; Addis, D.R.; Ford, J.H.; Schacter, D.L.; Giovanello, K.S

2014-01-01

Recent evidence suggests that our capacities to remember the past and to imagine what might happen in the future largely depend on the same core brain network that includes the middle temporal lobe, the posterior cingulate/retrosplenial cortex, the inferior parietal lobe, the medial prefrontal cortex, and the lateral temporal cortex. However, the extent to which regions of this core brain network are also responsible for our capacity to think about what could have happened in our past, yet did not occur (i.e., episodic counterfactual thinking), is still unknown. The present study examined this issue. Using a variation of the experimental recombination paradigm (Addis et al., 2009), participants were asked both to remember personal past events and to envision alternative outcomes to such events while undergoing functional magnetic resonance imaging. Three sets of analyses were performed on the imaging data in order to investigate two related issues. First, a mean-centered spatiotemporal partial least square (PLS) analysis identified a pattern of brain activity across regions of the core network that was common to episodic memory and episodic counterfactual thinking. Second, a non-rotated PLS analysis identified two different patterns of brain activity for likely and unlikely episodic counterfactual thoughts, with the former showing significant overlap with the set of regions engaged during episodic recollection. Finally, a parametric modulation was conducted to explore the differential engagement of brain regions during counterfactual thinking, revealing that areas such as the parahippocampal gyrus and the right hippocampus were modulated by the subjective likelihood of counterfactual simulations. These results suggest that episodic counterfactual thinking engages regions that form the core brain network, and also that the subjective likelihood of our counterfactual thoughts modulates the engagement of different areas within this set of regions. PMID:23376052

Growth-related neural reorganization and the autism phenotype: a test of the hypothesis that altered brain growth leads to altered connectivity

PubMed Central

Lewis, John D.; Elman, Jeffrey L.

2009-01-01

Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico-cortical connectivity. Differences in brain size during development will alter the relative cost and effectiveness of short- and long-distance connections, and should thus impact the growth and retention of connections. Reduced brain size should favor long-distance connectivity; brain overgrowth should favor short-distance connectivity; and inconsistent deviations from the normal growth trajectory – as occurs in autism – should result in potentially disruptive changes to established patterns of functional and physical connectivity during development. To explore this hypothesis, neural networks which modeled inter-hemispheric interaction were grown at the rate of either typically developing children or children with autism. The influence of the length of the inter-hemispheric connections was analyzed at multiple developmental time-points. The networks that modeled autistic growth were less affected by removal of the inter-hemispheric connections than those that modeled normal growth – indicating a reduced reliance on long-distance connections – for short response times, and this difference increased substantially at approximately 24 simulated months of age. The performance of the networks showed a corresponding decline during development. And direct analysis of the connection weights showed a parallel reduction in connectivity. These modeling results support the hypothesis that the deviant growth trajectory in autism spectrum disorders may lead to a disruption of established patterns of functional connectivity during development, with potentially negative behavioral consequences, and a subsequent reduction in physical connectivity. The results are discussed in relation to the growing body of evidence of reduced functional and structural connectivity in autism, and in relation to the behavioral phenotype, particularly the developmental aspects. PMID:18171375

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

PubMed Central

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

2010-01-01

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

Weak task-related modulation and stimulus representations during arithmetic problem solving in children with developmental dyscalculia

PubMed Central

Ashkenazi, Sarit; Rosenberg-Lee, Miriam; Tenison, Caitlin; Menon, Vinod

2015-01-01

Developmental dyscalculia (DD) is a disability that impacts math learning and skill acquisition in school-age children. Here we investigate arithmetic problem solving deficits in young children with DD using univariate and multivariate analysis of fMRI data. During fMRI scanning, 17 children with DD (ages 7–9, grades 2 and 3) and 17 IQ- and reading ability-matched typically developing (TD) children performed complex and simple addition problems which differed only in arithmetic complexity. While the TD group showed strong modulation of brain responses with increasing arithmetic complexity, children with DD failed to show such modulation. Children with DD showed significantly reduced activation compared to TD children in the intraparietal sulcus, superior parietal lobule, supramarginal gyrus and bilateral dorsolateral prefrontal cortex in relation to arithmetic complexity. Critically, multivariate representational similarity revealed that brain response patterns to complex and simple problems were less differentiated in the DD group in bilateral anterior IPS, independent of overall differences in signal level. Taken together, these results show that children with DD not only under-activate key brain regions implicated in mathematical cognition, but they also fail to generate distinct neural responses and representations for different arithmetic problems. Our findings provide novel insights into the neural basis of DD. PMID:22682904

Weak task-related modulation and stimulus representations during arithmetic problem solving in children with developmental dyscalculia.

PubMed

Ashkenazi, Sarit; Rosenberg-Lee, Miriam; Tenison, Caitlin; Menon, Vinod

2012-02-15

Developmental dyscalculia (DD) is a disability that impacts math learning and skill acquisition in school-age children. Here we investigate arithmetic problem solving deficits in young children with DD using univariate and multivariate analysis of fMRI data. During fMRI scanning, 17 children with DD (ages 7-9, grades 2 and 3) and 17 IQ- and reading ability-matched typically developing (TD) children performed complex and simple addition problems which differed only in arithmetic complexity. While the TD group showed strong modulation of brain responses with increasing arithmetic complexity, children with DD failed to show such modulation. Children with DD showed significantly reduced activation compared to TD children in the intraparietal sulcus, superior parietal lobule, supramarginal gyrus and bilateral dorsolateral prefrontal cortex in relation to arithmetic complexity. Critically, multivariate representational similarity revealed that brain response patterns to complex and simple problems were less differentiated in the DD group in bilateral anterior IPS, independent of overall differences in signal level. Taken together, these results show that children with DD not only under-activate key brain regions implicated in mathematical cognition, but they also fail to generate distinct neural responses and representations for different arithmetic problems. Our findings provide novel insights into the neural basis of DD. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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

2011-01-01

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

The Response of the Left Ventral Attentional System to Invalid Targets and its Implication for the Spatial Neglect Syndrome: a Multivariate fMRI Investigation.

PubMed

Silvetti, Massimo; Lasaponara, Stefano; Lecce, Francesca; Dragone, Alessio; Macaluso, Emiliano; Doricchi, Fabrizio

2016-12-01

In humans, invalid visual targets that mismatch spatial expectations induced by attentional cues are considered to selectively engage a right hemispheric "reorienting" network that includes the temporal parietal junction (TPJ), the inferior frontal gyrus (IFG), and the medial frontal gyrus (MFG). However, recent findings suggest that this hemispheric dominance is not absolute and that it is rather observed because the TPJ and IFG areas in the left hemisphere are engaged both by invalid and valid cued targets. Because of this, the BOLD response of the left hemisphere to invalid targets is usually cancelled out by the standard "invalid versus valid" contrast used in functional magnetic resonance imaging investigations of spatial attention. Here, we used multivariate pattern recognition analysis (MVPA) to gain finer insight into the role played by the left TPJ and IFG in reorienting to invalid targets. We found that in left TPJ and IFG blood oxygen level-dependent (BOLD) responses to invalid and valid targets were associated to different patterns of neural activity, possibly reflecting the presence of functionally distinct neuronal populations. Pattern segregation was significant at group level, it was present in almost all of the participants to the study and was observed both for targets in the left and right side of space. A control whole-brain MVPA ("Searchlight" analysis) confirmed the results obtained in predefined regions of interest and highlighted that also other areas, that is, superior parietal and frontal-polar cortex, show different patterns of BOLD response to valid and invalid targets. These results confirm and expand previous evidence highlighting the involvement of the left hemisphere in reorienting of visual attention (Doricchi et al. 2010; Dragone et al. 2015). These findings suggest that asymmetrical reorienting deficits suffered by right brain damaged patients with left spatial neglect, who have severe impairments in contralesional reorienting and less severe impairments in ipsilesional reorienting, are due to preserved reorienting abilities in the intact left hemisphere. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sex Differences in Nucleus Accumbens Transcriptome Profiles Associated with Susceptibility versus Resilience to Subchronic Variable Stress.

PubMed

Hodes, Georgia E; Pfau, Madeline L; Purushothaman, Immanuel; Ahn, H Francisca; Golden, Sam A; Christoffel, Daniel J; Magida, Jane; Brancato, Anna; Takahashi, Aki; Flanigan, Meghan E; Ménard, Caroline; Aleyasin, Hossein; Koo, Ja Wook; Lorsch, Zachary S; Feng, Jian; Heshmati, Mitra; Wang, Minghui; Turecki, Gustavo; Neve, Rachel; Zhang, Bin; Shen, Li; Nestler, Eric J; Russo, Scott J

2015-12-16

Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability. Women have a higher incidence of depression than men. However, preclinical models, the first step in developing new diagnostics and therapeutics, have been performed mainly on male subjects. Using a stress-based animal model of depression that causes behavioral effects in females but not males, we demonstrate a sex-specific transcriptional profile in brain reward circuitry. This transcriptional profile can be altered by removal of an epigenetic mechanism, which normally suppresses DNA transcription, creating a hybrid male/female transcriptional pattern. Removal of this epigenetic mechanism also induces behavioral resilience to stress in females. These findings shed new light onto molecular factors controlling sex differences in stress response. Copyright © 2015 the authors 0270-6474/15/3516363-15$15.00/0.

Sex Differences in Nucleus Accumbens Transcriptome Profiles Associated with Susceptibility versus Resilience to Subchronic Variable Stress

PubMed Central

Hodes, Georgia E.; Pfau, Madeline L.; Purushothaman, Immanuel; Ahn, H. Francisca; Golden, Sam A.; Christoffel, Daniel J.; Magida, Jane; Brancato, Anna; Takahashi, Aki; Flanigan, Meghan E.; Ménard, Caroline; Aleyasin, Hossein; Koo, Ja Wook; Lorsch, Zachary S.; Feng, Jian; Heshmati, Mitra; Wang, Minghui; Turecki, Gustavo; Neve, Rachel; Zhang, Bin; Shen, Li; Nestler, Eric J.

2015-01-01

Depression and anxiety disorders are more prevalent in females, but the majority of research in animal models, the first step in finding new treatments, has focused predominantly on males. Here we report that exposure to subchronic variable stress (SCVS) induces depression-associated behaviors in female mice, whereas males are resilient as they do not develop these behavioral abnormalities. In concert with these different behavioral responses, transcriptional analysis of nucleus accumbens (NAc), a major brain reward region, by use of RNA sequencing (RNA-seq) revealed markedly different patterns of stress regulation of gene expression between the sexes. Among the genes displaying sex differences was DNA methyltransferase 3a (Dnmt3a), which shows a greater induction in females after SCVS. Interestingly, Dnmt3a expression levels were increased in the NAc of depressed humans, an effect seen in both males and females. Local overexpression of Dnmt3a in NAc rendered male mice more susceptible to SCVS, whereas Dnmt3a knock-out in this region rendered females more resilient, directly implicating this gene in stress responses. Associated with this enhanced resilience of female mice upon NAc knock-out of Dnmt3a was a partial shift of the NAc female transcriptome toward the male pattern after SCVS. These data indicate that males and females undergo different patterns of transcriptional regulation in response to stress and that a DNA methyltransferase in NAc contributes to sex differences in stress vulnerability. SIGNIFICANCE STATEMENT Women have a higher incidence of depression than men. However, preclinical models, the first step in developing new diagnostics and therapeutics, have been performed mainly on male subjects. Using a stress-based animal model of depression that causes behavioral effects in females but not males, we demonstrate a sex-specific transcriptional profile in brain reward circuitry. This transcriptional profile can be altered by removal of an epigenetic mechanism, which normally suppresses DNA transcription, creating a hybrid male/female transcriptional pattern. Removal of this epigenetic mechanism also induces behavioral resilience to stress in females. These findings shed new light onto molecular factors controlling sex differences in stress response. PMID:26674863

The voices of seduction: cross-gender effects in processing of erotic prosody

PubMed Central

Ethofer, Thomas; Wiethoff, Sarah; Anders, Silke; Kreifelts, Benjamin; Grodd, Wolfgang

2007-01-01

Gender specific differences in cognitive functions have been widely discussed. Considering social cognition such as emotion perception conveyed by non-verbal cues, generally a female advantage is assumed. In the present study, however, we revealed a cross-gender interaction with increasing responses to the voice of opposite sex in male and female subjects. This effect was confined to erotic tone of speech in behavioural data and haemodynamic responses within voice sensitive brain areas (right middle superior temporal gyrus). The observed response pattern, thus, indicates a particular sensitivity to emotional voices that have a high behavioural relevance for the listener. PMID:18985138

Neural mechanisms of anger regulation as a function of genetic risk for violence.

PubMed

Alia-Klein, Nelly; Goldstein, Rita Z; Tomasi, Dardo; Woicik, Patricia A; Moeller, Scott J; Williams, Benjamin; Craig, Ian W; Telang, Frank; Biegon, Anat; Wang, Gene-Jack; Fowler, Joanna S; Volkow, Nora D

2009-06-01

Genetic risk may predispose individuals to compromised anger regulation, potentially through modulation of brain responses to emotionally evocative stimuli. Emphatically expressed, the emotional word No can prohibit behavior through conditioning. In a recent functional magnetic resonance imaging study, the authors showed that healthy males attribute negative valence to No while showing a lateral orbitofrontal response that correlated with their self-reported anger control. Here, the authors examined the influence of the monoamine oxidase A (MAOA) gene (low vs. high transcription variants) on brain response to No and in relationship to trait anger reactivity and control. The orbitofrontal response did not differ as a function of the genotype. Instead, carriers of the low-MAOA genotype had reduced left middle frontal gyrus activation to No compared with the high variant. Furthermore, only for carriers of the up low-MAOA genotype, left amygdala and posterior thalamic activation to No increased with anger reactivity. Thus, vulnerability to aggression in carriers of the low-MAOA genotype is supported by decreased middle frontal response to No and the unique amygdala/thalamus association pattern in this group with anger reactivity but not anger control.

Neural Mechanisms of Anger Regulation as a Function of Genetic Risk for Violence

PubMed Central

Alia-Klein, Nelly; Goldstein, Rita Z.; Tomasi, Dardo; Woicik, Patricia A.; Moeller, Scott J.; Williams, Benjamin; Craig, Ian W.; Telang, Frank; Biegon, Anat; Wang, Gene-Jack; Fowler, Joanna S.; Volkow, Nora D.

2009-01-01

Genetic risk may predispose individuals to compromised anger regulation, potentially through modulation of brain responses to emotionally evocative stimuli. Emphatically expressed, the emotional word No can prohibit behavior through conditioning. In a recent functional magnetic resonance imaging study, the authors showed that healthy males attribute negative valence to No while showing a lateral orbitofrontal response that correlated with their self-reported anger control. Here, the authors examined the influence of the monoamine oxidase A (MAOA) gene (low vs. high transcription variants) on brain response to No and in relationship to trait anger reactivity and control. The orbitofrontal response did not differ as a function of the genotype. Instead, carriers of the low-MAOA genotype had reduced left middle frontal gyrus activation to No compared with the high variant. Furthermore, only for carriers of theup low-MAOA genotype, left amygdala and posterior thalamic activation to No increased with anger reactivity. Thus, vulnerability to aggression in carriers of the low-MAOA genotype is supported by decreased middle frontal response to No and the unique amygdala/thalamus association pattern in this group with anger reactivity but not anger control. PMID:19485616

What has fMRI told us about the Development of Cognitive Control through Adolescence?

PubMed Central

Luna, Beatriz; Padmanabhan, Aarthi; O’Hearn, Kirsten

2009-01-01

Cognitive control, the ability to voluntarily guide our behavior, continues to improve throughout adolescence. Below we review the literature on age-related changes in brain function related to response inhibition and working memory, which support cognitive control. Findings from studies using functional magnetic imaging (fMRI) indicate that processing errors, sustaining a cognitive control state, and reaching adult levels of precision, persist through adolescence. Developmental changes in patterns of brain function suggest that core regions of the circuitry underlying cognitive control are on-line early in development. However, age-related changes in localized processes across the brain and in establishing long range connections that support top-down modulation of behavior may support more effective neural processing for optimal mature executive function. While great progress has been made in understanding the age-related changes in brain processes underlying cognitive development, there are still important challenges in developmental neuroimaging methods and the interpretation of data that need to be addressed. PMID:19765880

Analysis of creatine kinase activity with evaluation of protein expression under the effect of heat and hydrogen peroxide.

PubMed

Rakhmetov, A D; Pil, Lee Sang; Ostapchenko, L I; Zoon, Chae Ho

2015-01-01

Protein oxidation has detrimental effects on the brain functioning, which involves inhibition of the crucial enzyme, brain type creatine kinase (CKBB), responsible for the CK/phosphocreatine shuttle system. Here we demonstrate a susceptibility of CKBB to several ordinary stressors. In our study enzymatic activity of purified recombinant brain-type creatine kinase was evaluated. We assayed 30 nMconcentration of CKBB under normal and stress conditions. In the direction of phosphocreatine formation hydrogen peroxide and heat treatments altered CKBB activity down to 26 and 14%, respectively. Also, examination of immunoblotted membrane patterns by SDS-PAGE electrophoresis and western blot analysis showed a decrease in expression levels of intrinsic CKBB enzyme in HeLa andA549 cells. Hence, our results clearly show that cytosolic CKBB is extremely sensitive to oxidative stress and heat induced inactivation. Therefore, due to its susceptibility, this enzyme may be defined as a potential target in brain damage.

Persistent Postconcussive Symptoms Are Accompanied by Decreased Functional Brain Oxygenation.

PubMed

Helmich, Ingo; Saluja, Rajeet S; Lausberg, Hedda; Kempe, Mathias; Furley, Philip; Berger, Alisa; Chen, Jen-Kai; Ptito, Alain

2015-01-01

Diagnostic methods are considered a major concern in the determination of mild traumatic brain injury. The authors examined brain oxygenation patterns in subjects with severe and minor persistent postconcussive difficulties and a healthy control group during working memory tasks in prefrontal brain regions using functional near-infrared spectroscopy. The results demonstrated decreased working memory performances among concussed subjects with severe postconcussive symptoms that were accompanied by decreased brain oxygenation patterns. An association appears to exist between decreased brain oxygenation, poor performance of working memory tasks, and increased symptom severity scores in subjects suffering from persistent postconcussive symptoms.

Spatial band-pass filtering aids decoding musical genres from auditory cortex 7T fMRI.

PubMed

Sengupta, Ayan; Pollmann, Stefan; Hanke, Michael

2018-01-01

Spatial filtering strategies, combined with multivariate decoding analysis of BOLD images, have been used to investigate the nature of the neural signal underlying the discriminability of brain activity patterns evoked by sensory stimulation -- primarily in the visual cortex. Reported evidence indicates that such signals are spatially broadband in nature, and are not primarily comprised of fine-grained activation patterns. However, it is unclear whether this is a general property of the BOLD signal, or whether it is specific to the details of employed analyses and stimuli. Here we performed an analysis of publicly available, high-resolution 7T fMRI on the response BOLD response to musical genres in primary auditory cortex that matches a previously conducted study on decoding visual orientation from V1.  The results show that the pattern of decoding accuracies with respect to different types and levels of spatial filtering is comparable to that obtained from V1, despite considerable differences in the respective cortical circuitry.

Spatial patterns of brain atrophy in MCI patients, identified via high-dimensional pattern classification, predict subsequent cognitive decline

PubMed Central

Fan, Yong; Batmanghelich, Nematollah; Clark, Chris M.; Davatzikos, Christos

2010-01-01

Spatial patterns of brain atrophy in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) were measured via methods of computational neuroanatomy. These patterns were spatially complex and involved many brain regions. In addition to the hippocampus and the medial temporal lobe gray matter, a number of other regions displayed significant atrophy, including orbitofrontal and medial-prefrontal grey matter, cingulate (mainly posterior), insula, uncus, and temporal lobe white matter. Approximately 2/3 of the MCI group presented patterns of atrophy that overlapped with AD, whereas the remaining 1/3 overlapped with cognitively normal individuals, thereby indicating that some, but not all, MCI patients have significant and extensive brain atrophy in this cohort of MCI patients. Importantly, the group with AD-like patterns presented much higher rate of MMSE decline in follow-up visits; conversely, pattern classification provided relatively high classification accuracy (87%) of the individuals that presented relatively higher MMSE decline within a year from baseline. High-dimensional pattern classification, a nonlinear multivariate analysis, provided measures of structural abnormality that can potentially be useful for individual patient classification, as well as for predicting progression and examining multivariate relationships in group analyses. PMID:18053747

Geriatric neuro-oncology: from mythology to biology.

PubMed

Weller, Michael; Platten, Michael; Roth, Patrick; Wick, Wolfgang

2011-12-01

Age has remained one of the most important determinants of risk for the development of certain brain tumors, of benefit from and tolerance of brain tumor treatment, and overall outcome. Regarding these three aspects, there are major differences across the spectrum of primary brain tumors depending on specific histology. Here, we review recent advances in understanding the biological basis of the prognostic marker 'age' in neuro-oncology. Contemporary population-based studies confirm the strong prognostic impact of age in many brain tumors. Elderly patients continue to be treated less aggressively than younger patients with the same tumors. However, biological factors may contribute to the negative prognostic impact of age. For instance, among gliomas, mutations of the isocitrate dehydrogenase genes, which are prognostically favorable, are much more common in younger patients. Moreover, complete responses defined by neuroimaging were much less durable in elderly as opposed to younger patients with primary central nervous system lymphoma in the German Primary Central Nervous System Lymphoma Study Group trial. A combination of age-adapted patterns of care and treatment-independent, tumor-intrinsic factors contributes to the poorer outcome of elderly patients with brain tumors. These factors need to be better distinguished and understood in order to improve outcome in elderly brain tumor patients.

Does my brain want what my eyes like? - How food liking and choice influence spatio-temporal brain dynamics of food viewing.

PubMed

Bielser, Marie-Laure; Crézé, Camille; Murray, Micah M; Toepel, Ulrike

2016-12-01

How food valuation and decision-making influence the perception of food is of major interest to better understand food intake behavior and, by extension, body weight management. Our study investigated behavioral responses and spatio-temporal brain dynamics by means of visual evoked potentials (VEPs) in twenty-two normal-weight participants when viewing pairs of food photographs. Participants rated how much they liked each food item (valuation) and subsequently chose between the two alternative food images. Unsurprisingly, strongly liked foods were also chosen most often. Foods were rated faster as strongly liked than as mildly liked or disliked irrespective of whether they were subsequently chosen over an alternative. Moreover, strongly liked foods were subsequently also chosen faster than the less liked alternatives. Response times during valuation and choice were positively correlated, but only when foods were liked; the faster participants rated foods as strongly liked, the faster they were in choosing the food item over an alternative. VEP modulations by the level of liking attributed as well as the subsequent choice were found as early as 135-180ms after food image onset. Analyses of neural source activity patterns over this time interval revealed an interaction between liking and the subsequent choice within the insula, dorsal frontal and superior parietal regions. The neural responses to food viewing were found to be modulated by the attributed level of liking only when foods were chosen, not when they were dismissed for an alternative. Therein, the responses to disliked foods were generally greater than those to foods that were liked more. Moreover, the responses to disliked but chosen foods were greater than responses to disliked foods which were subsequently dismissed for an alternative offer. Our findings show that the spatio-temporal brain dynamics to food viewing are immediately influenced both by how much foods are liked and by choices taken on them. These valuation and choice processes are subserved by brain regions involved in salience and reward attribution as well as in decision-making processes, which are likely to influence prospective dietary choices in everyday life. Copyright © 2015 Elsevier Inc. All rights reserved.

Lateralized responses during covert attention are modulated by target eccentricity.

PubMed

Bahramisharif, Ali; Heskes, Tom; Jensen, Ole; van Gerven, Marcel A J

2011-03-10

Various studies have demonstrated that covert attention to different locations in the visual field can be used as a control signal for brain computer interfacing. It is well known that when covert attention is directed to the left visual hemifield, posterior alpha activity decreases in the right hemisphere while simultaneously increasing in the left hemisphere and vice versa. However, it remains unknown if and how the classical lateralization pattern depends on the eccentricity of the locations to which one attends. In this paper we study the effect of target eccentricity on the performance of a brain computer interface system that is driven by covert attention. Results show that the lateralization pattern becomes more pronounced as target eccentricity increases and suggest that in the current design the minimum eccentricity for having an acceptable classification performance for two targets at equal distance from fixation in opposite hemifields is about 6° of visual angle. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.