Toll-like receptor 4 enhancement of non-NMDA synaptic currents increases dentate excitability after brain injury.

PubMed

Li, Ying; Korgaonkar, Akshata A; Swietek, Bogumila; Wang, Jianfeng; Elgammal, Fatima S; Elkabes, Stella; Santhakumar, Vijayalakshmi

2015-02-01

Concussive brain injury results in neuronal degeneration, microglial activation and enhanced excitability in the hippocampal dentate gyrus, increasing the risk for epilepsy and memory dysfunction. Endogenous molecules released during injury can activate innate immune responses including toll-like receptor 4 (TLR4). Recent studies indicate that immune mediators can modulate neuronal excitability. Since non-specific agents that reduce TLR4 signaling can limit post-traumatic neuropathology, we examined whether TLR4 signaling contributes to early changes in dentate excitability after brain injury. Concussive brain injury caused a transient increase in hippocampal TLR4 expression within 4h, which peaked at 24h. Post-injury increase in TLR4 expression in the dentate gyrus was primarily neuronal and persisted for one week. Acute, in vitro treatment with TLR4 ligands caused bidirectional modulation of dentate excitability in control and brain-injured rats, with a reversal in the direction of modulation after brain injury. TLR4 antagonists decreased, and agonist increased, afferent-evoked dentate excitability one week after brain injury. NMDA receptor antagonist did not occlude the ability of LPS-RS, a TLR4 antagonist, to decrease post-traumatic dentate excitability. LPS-RS failed to modulate granule cell NMDA EPSCs but decreased perforant path-evoked non-NMDA EPSC peak amplitude and charge transfer in both granule cells and mossy cells. Our findings indicate an active role for TLR4 signaling in early post-traumatic dentate hyperexcitability. The novel TLR4 modulation of non-NMDA glutamatergic currents, identified herein, could represent a general mechanism by which immune activation influences neuronal excitability in neurological disorders that recruit sterile inflammatory responses. Copyright © 2014 Elsevier Inc. All rights reserved.

Ketamine modulation of the haemodynamic response to spreading depolarization in the gyrencephalic swine brain

PubMed Central

Santos, Edgar; Schöll, Michael; Kunzmann, Kevin; Stock, Christian; Silos, Humberto; Unterberg, Andreas W; Sakowitz, Oliver W

2016-01-01

Spreading depolarization (SD) generates significant alterations in cerebral haemodynamics, which can have detrimental consequences on brain function and integrity. Ketamine has shown an important capacity to modulate SD; however, its impact on SD haemodynamic response is incompletely understood. We investigated the effect of two therapeutic ketamine dosages, a low-dose of 2 mg/kg/h and a high-dose of 4 mg/kg/h, on the haemodynamic response to SD in the gyrencephalic swine brain. Cerebral blood volume, pial arterial diameter and cerebral blood flow were assessed through intrinsic optical signal imaging and laser-Doppler flowmetry. Our findings indicate that frequent SDs caused a persistent increase in the baseline pial arterial diameter, which can lead to a diminished capacity to further dilate. Ketamine infused at a low-dose reduced the hyperemic/vasodilative response to SD; however, it did not alter the subsequent oligemic/vasoconstrictive response. This low-dose did not prevent the baseline diameter increase and the diminished dilative capacity. Only infusion of ketamine at a high-dose suppressed SD and the coupled haemodynamic response. Therefore, the haemodynamic response to SD can be modulated by continuous infusion of ketamine. However, its use in pathological models needs to be explored to corroborate its possible clinical benefit. PMID:27126324

Ketamine modulation of the haemodynamic response to spreading depolarization in the gyrencephalic swine brain.

PubMed

Sánchez-Porras, Renán; Santos, Edgar; Schöll, Michael; Kunzmann, Kevin; Stock, Christian; Silos, Humberto; Unterberg, Andreas W; Sakowitz, Oliver W

2017-05-01

Spreading depolarization (SD) generates significant alterations in cerebral haemodynamics, which can have detrimental consequences on brain function and integrity. Ketamine has shown an important capacity to modulate SD; however, its impact on SD haemodynamic response is incompletely understood. We investigated the effect of two therapeutic ketamine dosages, a low-dose of 2 mg/kg/h and a high-dose of 4 mg/kg/h, on the haemodynamic response to SD in the gyrencephalic swine brain. Cerebral blood volume, pial arterial diameter and cerebral blood flow were assessed through intrinsic optical signal imaging and laser-Doppler flowmetry. Our findings indicate that frequent SDs caused a persistent increase in the baseline pial arterial diameter, which can lead to a diminished capacity to further dilate. Ketamine infused at a low-dose reduced the hyperemic/vasodilative response to SD; however, it did not alter the subsequent oligemic/vasoconstrictive response. This low-dose did not prevent the baseline diameter increase and the diminished dilative capacity. Only infusion of ketamine at a high-dose suppressed SD and the coupled haemodynamic response. Therefore, the haemodynamic response to SD can be modulated by continuous infusion of ketamine. However, its use in pathological models needs to be explored to corroborate its possible clinical benefit.

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.

Low frequency steady-state brain responses modulate large scale functional networks in a frequency-specific means.

PubMed

Wang, Yi-Feng; Long, Zhiliang; Cui, Qian; Liu, Feng; Jing, Xiu-Juan; Chen, Heng; Guo, Xiao-Nan; Yan, Jin H; Chen, Hua-Fu

2016-01-01

Neural oscillations are essential for brain functions. Research has suggested that the frequency of neural oscillations is lower for more integrative and remote communications. In this vein, some resting-state studies have suggested that large scale networks function in the very low frequency range (<1 Hz). However, it is difficult to determine the frequency characteristics of brain networks because both resting-state studies and conventional frequency tagging approaches cannot simultaneously capture multiple large scale networks in controllable cognitive activities. In this preliminary study, we aimed to examine whether large scale networks can be modulated by task-induced low frequency steady-state brain responses (lfSSBRs) in a frequency-specific pattern. In a revised attention network test, the lfSSBRs were evoked in the triple network system and sensory-motor system, indicating that large scale networks can be modulated in a frequency tagging way. Furthermore, the inter- and intranetwork synchronizations as well as coherence were increased at the fundamental frequency and the first harmonic rather than at other frequency bands, indicating a frequency-specific modulation of information communication. However, there was no difference among attention conditions, indicating that lfSSBRs modulate the general attention state much stronger than distinguishing attention conditions. This study provides insights into the advantage and mechanism of lfSSBRs. More importantly, it paves a new way to investigate frequency-specific large scale brain activities. © 2015 Wiley Periodicals, Inc.

Modulation of thermal pain-related brain activity with virtual reality: evidence from fMRI.

PubMed

Hoffman, Hunter G; Richards, Todd L; Coda, Barbara; Bills, Aric R; Blough, David; Richards, Anne L; Sharar, Sam R

2004-06-07

This study investigated the neural correlates of virtual reality analgesia. Virtual reality significantly reduced subjective pain ratings (i.e. analgesia). Using fMRI, pain-related brain activity was measured for each participant during conditions of no virtual reality and during virtual reality (order randomized). As predicted, virtual reality significantly reduced pain-related brain activity in all five regions of interest; the anterior cingulate cortex, primary and secondary somatosensory cortex, insula, and thalamus (p<0.002, corrected). Results showed direct modulation of human brain pain responses by virtual reality distraction. Copyright 2004 Lippincott Williams and Wilkins

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

PubMed

Jirakittayakorn, Nantawachara; Wongsawat, Yodchanan

2015-01-01

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

Brain mitochondrial bioenergetics change with rapid and prolonged shifts in aggression in the honey bee, Apis mellifera.

PubMed

Rittschof, Clare C; Vekaria, Hemendra J; Palmer, Joseph H; Sullivan, Patrick G

2018-04-25

Neuronal function demands high-level energy production, and as such, a decline in mitochondrial respiration characterizes brain injury and disease. A growing number of studies, however, link brain mitochondrial function to behavioral modulation in non-diseased contexts. In the honey bee, we show for the first time that an acute social interaction, which invokes an aggressive response, may also cause a rapid decline in brain mitochondrial bioenergetics. The degree and speed of this decline has only been previously observed in the context of brain injury. Furthermore, in the honey bee, age-related increases in aggressive tendency are associated with increased baseline brain mitochondrial respiration, as well as increased plasticity in response to metabolic fuel type in vitro Similarly, diet restriction and ketone body feeding, which commonly enhance mammalian brain mitochondrial function in vivo , cause increased aggression. Thus, even in normal behavioral contexts, brain mitochondria show a surprising degree of variation in function over both rapid and prolonged time scales, with age predicting both baseline function and plasticity in function. These results suggest that mitochondrial function is integral to modulating aggression-related neuronal signaling. We hypothesize that variation in function reflects mitochondrial calcium buffering activity, and that shifts in mitochondrial function signal to the neuronal soma to regulate gene expression and neural energetic state. Modulating brain energetic state is emerging as a critical component of the regulation of behavior in non-diseased contexts. © 2018. Published by The Company of Biologists Ltd.

Central nervous system regulation of intestinal lipid and lipoprotein metabolism.

PubMed

Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

2016-02-01

In response to nutrient availability, the small intestine and brain closely communicate to modulate energy homeostasis and metabolism. The gut-brain axis involves complex nutrient sensing mechanisms and an integration of neuronal and hormonal signaling. This review summarizes recent evidence implicating the gut-brain axis in regulating lipoprotein metabolism, with potential implications for the dyslipidemia of insulin resistant states. The intestine and brain possess distinct mechanisms for sensing lipid availability, which triggers subsequent regulation of feeding, glucose homeostasis, and adipose tissue metabolism. More recently, central receptors, neuropeptides, and gut hormones that communicate with the brain have been shown to modulate hepatic and intestinal lipoprotein metabolism via parasympathetic and sympathetic signaling. Gut-derived glucagon-like peptides appear to be particularly important in modulating the intestinal secretion of chylomicron particles via a novel brain-gut axis. Dysregulation of these pathways may contribute to postprandial diabetic dyslipidemia. Emerging evidence implicates the central and enteric nervous systems in controlling many aspects of lipid and lipoprotein metabolism. Bidirectional communication between the gut and brain involving neuronal pathways and gut peptides is critical for regulating feeding and metabolism, and forms a neuroendocrine circuit to modulate dietary fat absorption and intestinal production of atherogenic chylomicron particles.

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.

Neural markers of social and monetary rewards in children with Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

PubMed Central

Gonzalez-Gadea, Maria Luz; Sigman, Mariano; Rattazzi, Alexia; Lavin, Claudio; Rivera-Rei, Alvaro; Marino, Julian; Manes, Facundo; Ibanez, Agustin

2016-01-01

Recent theories of decision making propose a shared value-related brain mechanism for encoding monetary and social rewards. We tested this model in children with Attention-Deficit/Hyperactivity Disorder (ADHD), children with Autism Spectrum Disorder (ASD) and control children. We monitored participants’ brain dynamics using high density-electroencephalography while they played a monetary and social reward tasks. Control children exhibited a feedback Error-Related Negativity (fERN) modulation and Anterior Cingulate Cortex (ACC) source activation during both tasks. Remarkably, although cooperation resulted in greater losses for the participants, the betrayal options generated greater fERN responses. ADHD subjects exhibited an absence of fERN modulation and reduced ACC activation during both tasks. ASD subjects exhibited normal fERN modulation during monetary choices and inverted fERN/ACC responses in social options than did controls. These results suggest that in neurotypicals, monetary losses and observed disloyal social decisions induced similar activity in the brain value system. In ADHD children, difficulties in reward processing affected early brain signatures of monetary and social decisions. Conversely, ASD children showed intact neural markers of value-related monetary mechanisms, but no brain modulation by prosociality in the social task. These results offer insight into the typical and atypical developments of neural correlates of monetary and social reward processing. PMID:27464551

Social hierarchy modulates neural responses of empathy for pain

PubMed Central

Feng, Chunliang; Li, Zhihao; Feng, Xue; Wang, Lili; Tian, Tengxiang

2016-01-01

Recent evidence indicates that empathic responses to others’ pain are modulated by various situational and individual factors. However, few studies have examined how empathy and underlying brain functions are modulated by social hierarchies, which permeate human society with an enormous impact on social behavior and cognition. In this study, social hierarchies were established based on incidental skill in a perceptual task in which all participants were mediumly ranked. Afterwards, participants were scanned with functional magnetic resonance imaging while watching inferior-status or superior-status targets receiving painful or non-painful stimulation. The results revealed that painful stimulation applied to inferior-status targets induced higher activations in the anterior insula (AI) and anterior medial cingulate cortex (aMCC), whereas these empathic brain activations were significantly attenuated in response to superior-status targets’ pain. Further, this neural empathic bias to inferior-status targets was accompanied by stronger functional couplings of AI with brain regions important in emotional processing (i.e. thalamus) and cognitive control (i.e. middle frontal gyrus). Our findings indicate that emotional sharing with others’ pain is shaped by relative positions in a social hierarchy such that underlying empathic neural responses are biased toward inferior-status compared with superior-status individuals. PMID:26516169

An fMRI investigation into the effect of preceding stimuli during visual oddball tasks.

PubMed

Fajkus, Jiří; Mikl, Michal; Shaw, Daniel Joel; Brázdil, Milan

2015-08-15

This study investigates the modulatory effect of stimulus sequence on neural responses to novel stimuli. A group of 34 healthy volunteers underwent event-related functional magnetic resonance imaging while performing a three-stimulus visual oddball task, involving randomly presented frequent stimuli and two types of infrequent stimuli - targets and distractors. We developed a modified categorization of rare stimuli that incorporated the type of preceding rare stimulus, and analyzed the event-related functional data according to this sequence categorization; specifically, we explored hemodynamic response modulation associated with increasing rare-to-rare stimulus interval. For two consecutive targets, a modulation of brain function was evident throughout posterior midline and lateral temporal cortex, while responses to targets preceded by distractors were modulated in a widely distributed fronto-parietal system. As for distractors that follow targets, brain function was modulated throughout a set of posterior brain structures. For two successive distractors, however, no significant modulation was observed, which is consistent with previous studies and our primary hypothesis. The addition of the aforementioned technique extends the possibilities of conventional oddball task analysis, enabling researchers to explore the effects of the whole range of rare stimuli intervals. This methodology can be applied to study a wide range of associated cognitive mechanisms, such as decision making, expectancy and attention. Copyright © 2015 Elsevier B.V. All rights reserved.

Individual Differences in Mathematical Competence Modulate Brain Responses to Arithmetic Errors: An fMRI Study

ERIC Educational Resources Information Center

Ansari, Daniel; Grabner, Roland H.; Koschutnig, Karl; Reishofer, Gernot; Ebner, Franz

2011-01-01

Data from both neuropsychological and neuroimaging studies have implicated the left inferior parietal cortex in calculation. Comparatively less attention has been paid to the neural responses associated with the commission of calculation errors and how the processing of arithmetic errors is modulated by individual differences in mathematical…

Identification of common coexpression modules based on quantitative network comparison.

PubMed

Jo, Yousang; Kim, Sanghyeon; Lee, Doheon

2018-06-13

Finding common molecular interactions from different samples is essential work to understanding diseases and other biological processes. Coexpression networks and their modules directly reflect sample-specific interactions among genes. Therefore, identification of common coexpression network or modules may reveal the molecular mechanism of complex disease or the relationship between biological processes. However, there has been no quantitative network comparison method for coexpression networks and we examined previous methods for other networks that cannot be applied to coexpression network. Therefore, we aimed to propose quantitative comparison methods for coexpression networks and to find common biological mechanisms between Huntington's disease and brain aging by the new method. We proposed two similarity measures for quantitative comparison of coexpression networks. Then, we performed experiments using known coexpression networks. We showed the validity of two measures and evaluated threshold values for similar coexpression network pairs from experiments. Using these similarity measures and thresholds, we quantitatively measured the similarity between disease-specific and aging-related coexpression modules and found similar Huntington's disease-aging coexpression module pairs. We identified similar Huntington's disease-aging coexpression module pairs and found that these modules are related to brain development, cell death, and immune response. It suggests that up-regulated cell signalling related cell death and immune/ inflammation response may be the common molecular mechanisms in the pathophysiology of HD and normal brain aging in the frontal cortex.

Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala and ventral striatum

PubMed Central

Fletcher, PC; Napolitano, A; Skeggs, A; Miller, SR; Delafont, B; Cambridge, VC; de Wit, S; Nathan, PJ; Brooke, A; O’Rahilly, S; Farooqi, IS; Bullmore, ET

2012-01-01

We used fMRI to explore brain responses to food images in overweight humans, examining independently the impact of a pre-scan meal (“satiety”) and the anti-obesity drug sibutramine, a serotonin and noradrenaline reuptake inhibitor. We identified significantly different responses to these manipulations in amygdala, hypothalamus and ventral striatum. Each region was specifically responsive to high calorie compared to low calorie food images. However, the ventral striatal response was attenuated by satiety (but unaffected by sibutramine) while the hypothalamic and amygdala responses were attenuated by drug but unaffected by satiety. Direct assessment of regional interactions confirmed the significance of this double dissociation. We explored the regional responses in greater detail by determining whether they were predictive of eating behaviour and weight change. We observed that across the different regions, the individual-specific magnitude of drug- and satiety-induced modulation was associated with both variables: the sibutramine-induced modulation of the hypothalamic response was correlated with the drug’s impact on both weight and subsequently-measured ad libitum eating. The satiety-induced modulation of striatal response also correlated with subsequent ad lib eating. These results suggest that hypothalamus and amygdala have roles in the control of food intake that are distinct from those of ventral striatum. Furthermore, they support a regionally-specific effect on brain function through which sibutramine exerts its clinical effect. PMID:20980590

Stable long-term chronic brain mapping at the single-neuron level.

PubMed

Fu, Tian-Ming; Hong, Guosong; Zhou, Tao; Schuhmann, Thomas G; Viveros, Robert D; Lieber, Charles M

2016-10-01

Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning. Properties of acquired signals suggest robust tracking of the same neurons over this period. This recording and stimulation platform allowed us to evoke stable single-neuron responses to chronic electrical stimulation and to carry out longitudinal studies of brain aging in freely behaving mice. Such advantages could open up future studies in mapping and modulating changes associated with learning, aging and neurodegenerative diseases.

Encoding of frequency-modulation (FM) rates in human auditory cortex.

PubMed

Okamoto, Hidehiko; Kakigi, Ryusuke

2015-12-14

Frequency-modulated sounds play an important role in our daily social life. However, it currently remains unclear whether frequency modulation rates affect neural activity in the human auditory cortex. In the present study, using magnetoencephalography, we investigated the auditory evoked N1m and sustained field responses elicited by temporally repeated and superimposed frequency-modulated sweeps that were matched in the spectral domain, but differed in frequency modulation rates (1, 4, 16, and 64 octaves per sec). The results obtained demonstrated that the higher rate frequency-modulated sweeps elicited the smaller N1m and the larger sustained field responses. Frequency modulation rate had a significant impact on the human brain responses, thereby providing a key for disentangling a series of natural frequency-modulated sounds such as speech and music.

Inflammatory Responses in Brain Ischemia

PubMed Central

Kawabori, Masahito; Yenari, Midori A.

2017-01-01

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

Neural Dynamics Underlying Target Detection in the Human Brain

PubMed Central

Bansal, Arjun K.; Madhavan, Radhika; Agam, Yigal; Golby, Alexandra; Madsen, Joseph R.

2014-01-01

Sensory signals must be interpreted in the context of goals and tasks. To detect a target in an image, the brain compares input signals and goals to elicit the correct behavior. We examined how target detection modulates visual recognition signals by recording intracranial field potential responses from 776 electrodes in 10 epileptic human subjects. We observed reliable differences in the physiological responses to stimuli when a cued target was present versus absent. Goal-related modulation was particularly strong in the inferior temporal and fusiform gyri, two areas important for object recognition. Target modulation started after 250 ms post stimulus, considerably after the onset of visual recognition signals. While broadband signals exhibited increased or decreased power, gamma frequency power showed predominantly increases during target presence. These observations support models where task goals interact with sensory inputs via top-down signals that influence the highest echelons of visual processing after the onset of selective responses. PMID:24553944

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.

Task relevance modulates the behavioural and neural effects of sensory predictions

PubMed Central

Friston, Karl J.; Nobre, Anna C.

2017-01-01

The brain is thought to generate internal predictions to optimize behaviour. However, it is unclear whether predictions signalling is an automatic brain function or depends on task demands. Here, we manipulated the spatial/temporal predictability of visual targets, and the relevance of spatial/temporal information provided by auditory cues. We used magnetoencephalography (MEG) to measure participants’ brain activity during task performance. Task relevance modulated the influence of predictions on behaviour: spatial/temporal predictability improved spatial/temporal discrimination accuracy, but not vice versa. To explain these effects, we used behavioural responses to estimate subjective predictions under an ideal-observer model. Model-based time-series of predictions and prediction errors (PEs) were associated with dissociable neural responses: predictions correlated with cue-induced beta-band activity in auditory regions and alpha-band activity in visual regions, while stimulus-bound PEs correlated with gamma-band activity in posterior regions. Crucially, task relevance modulated these spectral correlates, suggesting that current goals influence PE and prediction signalling. PMID:29206225

Stress Response Recruits the Hippocampal Endocannabinoid System for the Modulation of Fear Memory

ERIC Educational Resources Information Center

Alvares, Lucas de Oliveira; Engelke, Douglas Senna; Diehl, Felipe; Scheffer-Teixeira, Robson; Haubrich, Josue; Cassini, Lindsey de Freitas; Molina, Victor Alejandro; Quillfeldt, Jorge Alberto

2010-01-01

The modulation of memory processes is one of the several functions of the endocannabinoid system (ECS) in the brain, with CB1 receptors highly expressed in areas such as the dorsal hippocampus. Experimental evidence suggested an important role of the ECS in aversively motivated memories. Similarly, glucocorticoids released in response to stress…

Perivascular Spaces--MRI Marker of Inflammatory Activity in the Brain?

ERIC Educational Resources Information Center

Wuerfel, Jens; Haertle, Mareile; Waiczies, Helmar; Tysiak, Eva; Bechmann, Ingo; Wernecke, Klaus D.; Zipp, Frauke; Paul, Friedemann

2008-01-01

The Virchow-Robin spaces (VRS), perivascular compartments surrounding small blood vessels as they penetrate the brain parenchyma, are increasingly recognized for their role in leucocyte trafficking as well as for their potential to modulate immune responses. In the present study, we investigated VRS numbers and volumes in different brain regions…

Psychoneuroimmunology - psyche and autoimmunity.

PubMed

Ziemssen, Tjalf

2012-01-01

Psychoneuroimmunology is a relatively young field of research that investigates interactions between central nervous and immune system. The brain modulates the immune system by the endocrine and autonomic nervous system. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and autoimmune disease. For several diseases, the relevance of psychoneuroimmunological findings has already been demonstrated.

Oxytocin influences processing of socially relevant cues in the ventral tegmental area of the human brain.

PubMed

Groppe, Sarah E; Gossen, Anna; Rademacher, Lena; Hahn, Alexa; Westphal, Luzie; Gründer, Gerhard; Spreckelmeyer, Katja N

2013-08-01

Evidence accumulates that the neuropeptide oxytocin plays an important role in mediating social interaction among humans and that a dysfunction in oxytocin-modulated brain mechanisms might lie at the core of disturbed social behavior in neuropsychiatric disease. Explanatory models suggest that oxytocin guides social approach and avoidance by modulating the perceived salience of socially meaningful cues. Animal data point toward the ventral tegmental area (VTA) as the brain site where this modulation takes place. We used functional magnetic resonance imaging and a social incentive delay task to test the hypothesis that oxytocin modulates the neural processing of socially relevant cues in the VTA, hereby facilitating behavioral response. Twenty-eight nulliparous women (not taking any hormones) received intranasal oxytocin or placebo in a double-blind randomized clinical trial with a parallel-group design. Oxytocin significantly enhanced VTA activation in response to cues signaling social reward (friendly face) or social punishment (angry face). Oxytocin effects on behavioral performance were modulated by individual differences in sociability with enhanced performance in women scoring low but decreased performance in women scoring high on self-reported measures of agreeableness. Our data provide evidence that the VTA is the human brain site where oxytocin attaches salience to socially relevant cues. This mechanism might play an important role in triggering motivation to react at the prospect of social reward or punishment. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Stress modulation of cognitive and affective processes

PubMed Central

CAMPEAU, SERGE; LIBERZON, ISRAEL; MORILAK, DAVID; RESSLER, KERRY

2012-01-01

This review summarizes the major discussion points of a symposium on stress modulation of cognitive and affective processes, which was held during the 2010 workshop on the neurobiology of stress (Boulder, CO, USA). The four discussants addressed a number of specific cognitive and affective factors that are modulated by exposure to acute or repeated stress. Dr David Morilak discussed the effects of various repeated stress situations on cognitive flexibility, as assessed with a rodent model of attentional set-shifting task, and how performance on slightly different aspects of this test is modulated by different prefrontal regions through monoaminergic neurotransmission. Dr Serge Campeau summarized the findings of several studies exploring a number of factors and brain regions that regulate habituation of various autonomic and neuroendocrine responses to repeated audiogenic stress exposures. Dr Kerry Ressler discussed a body of work exploring the modulation and extinction of fear memories in rodents and humans, especially focusing on the role of key neurotransmitter systems including excitatory amino acids and brain-derived neurotrophic factor. Dr Israel Liberzon presented recent results on human decision-making processes in response to exogenous glucocorticoid hormone administration. Overall, these discussions are casting a wider framework on the cognitive/affective processes that are distinctly regulated by the experience of stress and some of the brain regions and neurotransmitter systems associated with these effects. PMID:21790481

Social hierarchy modulates neural responses of empathy for pain.

PubMed

Feng, Chunliang; Li, Zhihao; Feng, Xue; Wang, Lili; Tian, Tengxiang; Luo, Yue-Jia

2016-03-01

Recent evidence indicates that empathic responses to others' pain are modulated by various situational and individual factors. However, few studies have examined how empathy and underlying brain functions are modulated by social hierarchies, which permeate human society with an enormous impact on social behavior and cognition. In this study, social hierarchies were established based on incidental skill in a perceptual task in which all participants were mediumly ranked. Afterwards, participants were scanned with functional magnetic resonance imaging while watching inferior-status or superior-status targets receiving painful or non-painful stimulation. The results revealed that painful stimulation applied to inferior-status targets induced higher activations in the anterior insula (AI) and anterior medial cingulate cortex (aMCC), whereas these empathic brain activations were significantly attenuated in response to superior-status targets' pain. Further, this neural empathic bias to inferior-status targets was accompanied by stronger functional couplings of AI with brain regions important in emotional processing (i.e. thalamus) and cognitive control (i.e. middle frontal gyrus). Our findings indicate that emotional sharing with others' pain is shaped by relative positions in a social hierarchy such that underlying empathic neural responses are biased toward inferior-status compared with superior-status individuals. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

[Renin-angiotensin-aldosterone system (RAAS) and its pharmacologic modulation].

PubMed

Giestas, Anabela; Palma, Isabel; Ramos, Maria Helena

2010-01-01

The renin-angiotensin-aldosterone system (RAAS) is a neuroendocrine complex system that regulates the modulation of salt and water homeostasis, and regulation of blood pressure. Through its multiple interactions it protects the endothelium, heart, brain and kidney. In addition, the RAAS regulates the vascular response to injury and inflammation. Chronic activation/dysregulation of the RAAS leads to hypertension and perpetuates a cascade of proinflammatory, prothrombotic and atherogenic effects associated with endorgan damage (heart, brain, kidney, endothelium). Consequently, the RAAS is an important therapeutic target in these situations. This article presents an overview of physiology, pathophysiology and pharmacologic modulation of the RAAS.

Emotion and sex of facial stimuli modulate conditional automaticity in behavioral and neuronal interference in healthy men.

PubMed

Kohn, Nils; Fernández, Guillén

2017-12-06

Our surrounding provides a host of sensory input, which we cannot fully process without streamlining and automatic processing. Levels of automaticity differ for different cognitive and affective processes. Situational and contextual interactions between cognitive and affective processes in turn influence the level of automaticity. Automaticity can be measured by interference in Stroop tasks. We applied an emotional version of the Stroop task to investigate how stress as a contextual factor influences the affective valence-dependent level of automaticity. 120 young, healthy men were investigated for behavioral and brain interference following a stress induction or control procedure in a counter-balanced cross-over-design. Although Stroop interference was always observed, sex and emotion of the face strongly modulated interference, which was larger for fearful and male faces. These effects suggest higher automaticity when processing happy and also female faces. Supporting behavioral patterns, brain data show lower interference related brain activity in executive control related regions in response to happy and female faces. In the absence of behavioral stress effects, congruent compared to incongruent trials (reverse interference) showed little to no deactivation under stress in response to happy female and fearful male trials. These congruency effects are potentially based on altered context- stress-related facial processing that interact with sex-emotion stereotypes. Results indicate that sex and facial emotion modulate Stroop interference in brain and behavior. These effects can be explained by altered response difficulty as a consequence of the contextual and stereotype related modulation of automaticity. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Role of the Brain's Endocannabinoid System in Pain and Its Modulation by Stress.

PubMed

Corcoran, Louise; Roche, Michelle; Finn, David P

2015-01-01

Stress has a complex, bidirectional modulatory influence on pain. Stress may either reduce (stress-induced analgesia) or exacerbate (stress-induced hyperalgesia) pain depending on the nature, duration, and intensity of the stressor. The endogenous cannabinoid (endocannabinoid) system is present throughout the neuroanatomical pathways that mediate and modulate responses to painful stimuli. The specific role of the endocannabinoid system in the brain in pain and the modulation of pain by stress is reviewed herein. We first provide a brief overview of the endocannabinoid system, followed by a review of the evidence that the brain's endocannabinoid system modulates pain. We provide a comprehensive evaluation of the role of the endocannabinoid system supraspinally, and particularly in the rostral ventromedial medulla, periaqueductal gray, amygdala, and prefrontal cortex, in pain, stress-induced analgesia, and stress-induced hyperalgesia. Increased understanding of endocannabinoid-mediated regulation of pain and its modulation by stress will inform the development of novel therapeutic approaches for pain and its comorbidity with stress-related disorders. © 2015 Elsevier Inc. All rights reserved.

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

PubMed

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

2009-08-01

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

Regional entropy of functional imaging signals varies differently in sensory and cognitive systems during propofol-modulated loss and return of behavioral responsiveness.

PubMed

Liu, Xiaolin; Lauer, Kathryn K; Ward, B Douglas; Roberts, Christopher J; Liu, Suyan; Gollapudy, Suneeta; Rohloff, Robert; Gross, William; Xu, Zhan; Chen, Shanshan; Wang, Lubin; Yang, Zheng; Li, Shi-Jiang; Binder, Jeffrey R; Hudetz, Anthony G

2018-05-08

The level and richness of consciousness depend on information integration in the brain. Altered interregional functional interactions may indicate disrupted information integration during anesthetic-induced unconsciousness. How anesthetics modulate the amount of information in various brain regions has received less attention. Here, we propose a novel approach to quantify regional information content in the brain by the entropy of the principal components of regional blood oxygen-dependent imaging signals during graded propofol sedation. Fifteen healthy individuals underwent resting-state scans in wakeful baseline, light sedation (conscious), deep sedation (unconscious), and recovery (conscious). Light sedation characterized by lethargic behavioral responses was associated with global reduction of entropy in the brain. Deep sedation with completely suppressed overt responsiveness was associated with further reductions of entropy in sensory (primary and higher sensory plus orbital prefrontal cortices) but not high-order cognitive (dorsal and medial prefrontal, cingulate, parietotemporal cortices and hippocampal areas) systems. Upon recovery of responsiveness, entropy was restored in the sensory but not in high-order cognitive systems. These findings provide novel evidence for a reduction of information content of the brain as a potential systems-level mechanism of reduced consciousness during propofol anesthesia. The differential changes of entropy in the sensory and high-order cognitive systems associated with losing and regaining overt responsiveness are consistent with the notion of "disconnected consciousness", in which a complete sensory-motor disconnection from the environment occurs with preserved internal mentation.

Differential Responses of Brain, Gonad and Muscle Steroid Levels to Changes in Social Status and Sex in a Sequential and Bidirectional Hermaphroditic Fish

PubMed Central

Lorenzi, Varenka; Earley, Ryan L.; Grober, Matthew S.

2012-01-01

Sex steroids can both modulate and be modulated by behavior, and their actions are mediated by complex interactions among multiple hormone sources and targets. While gonadal steroids delivered via circulation can affect behavior, changes in local brain steroid synthesis also can modulate behavior. The relative steroid load across different tissues and the association of these levels with rates of behavior have not been well studied. The bluebanded goby (Lythrypnus dalli) is a sex changing fish in which social status determines sexual phenotype. We examined changes in steroid levels in brain, gonad and body muscle at either 24 hours or 6 days after social induction of protogynous sex change, and from individuals in stable social groups not undergoing sex change. For each tissue, we measured levels of estradiol (E2), testosterone (T) and 11-ketotestosterone (KT). Females had more T than males in the gonads, and more E2 in all tissues but there was no sex difference in KT. For both sexes, E2 was higher in the gonad than in other tissues while androgens were higher in the brain. During sex change, brain T levels dropped while brain KT increased, and brain E2 levels did not change. We found a positive relationship between androgens and aggression in the most dominant females but only when the male was removed from the social group. The results demonstrate that steroid levels are responsive to changes in the social environment, and that their concentrations vary in different tissues. Also, we suggest that rapid changes in brain androgen levels might be important in inducing behavioral and/or morphological changes associated with protogynous sex change. PMID:23251444

Modulating the pituitary-adrenal response to stress

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.

1975-01-01

Serotonin is believed to be a transmitter or regulator of neuronal function. A possible relationship between the pituitary-adrenal secretion of steroids and brain serotonin in the rat was investigated by evaluating the effects of altering brain 5-hydroxy tryptamine (HT) levels on the daily fluctuation of plasma corticosterone and on the response of the pituitary-adrenal system to a stressful or noxious stimulus in the rat. The approach was either to inhibit brain 5-HT synthesis with para-chlorophenyl alanine or to raise its level with precursors such as tryptophan or 5-hydroxy tryptophan.

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

State-dependent changes in cortical gain control as measured by auditory evoked responses to varying intensity stimuli.

PubMed

Phillips, Derrick J; Schei, Jennifer L; Meighan, Peter C; Rector, David M

2011-11-01

Auditory evoked potential (AEP) components correspond to sequential activation of brain structures within the auditory pathway and reveal neural activity during sensory processing. To investigate state-dependent modulation of stimulus intensity response profiles within different brain structures, we assessed AEP components across both stimulus intensity and state. We implanted adult female Sprague-Dawley rats (N = 6) with electrodes to measure EEG, EKG, and EMG. Intermittent auditory stimuli (6-12 s) varying from 50 to 75 dBa were delivered over a 24-h period. Data were parsed into 2-s epochs and scored for wake/sleep state. All AEP components increased in amplitude with increased stimulus intensity during wake. During quiet sleep, however, only the early latency response (ELR) showed this relationship, while the middle latency response (MLR) increased at the highest 75 dBa intensity, and the late latency response (LLR) showed no significant change across the stimulus intensities tested. During rapid eye movement sleep (REM), both ELR and LLR increased, similar to wake, but MLR was severely attenuated. Stimulation intensity and the corresponding AEP response profile were dependent on both brain structure and sleep state. Lower brain structures maintained stimulus intensity and neural response relationships during sleep. This relationship was not observed in the cortex, implying state-dependent modification of stimulus intensity coding. Since AEP amplitude is not modulated by stimulus intensity during sleep, differences between paired 75/50 dBa stimuli could be used to determine state better than individual intensities.

Spectral-temporal EEG dynamics of speech discrimination processing in infants during sleep.

PubMed

Gilley, Phillip M; Uhler, Kristin; Watson, Kaylee; Yoshinaga-Itano, Christine

2017-03-22

Oddball paradigms are frequently used to study auditory discrimination by comparing event-related potential (ERP) responses from a standard, high probability sound and to a deviant, low probability sound. Previous research has established that such paradigms, such as the mismatch response or mismatch negativity, are useful for examining auditory processes in young children and infants across various sleep and attention states. The extent to which oddball ERP responses may reflect subtle discrimination effects, such as speech discrimination, is largely unknown, especially in infants that have not yet acquired speech and language. Mismatch responses for three contrasts (non-speech, vowel, and consonant) were computed as a spectral-temporal probability function in 24 infants, and analyzed at the group level by a modified multidimensional scaling. Immediately following an onset gamma response (30-50 Hz), the emergence of a beta oscillation (12-30 Hz) was temporally coupled with a lower frequency theta oscillation (2-8 Hz). The spectral-temporal probability of this coupling effect relative to a subsequent theta modulation corresponds with discrimination difficulty for non-speech, vowel, and consonant contrast features. The theta modulation effect suggests that unexpected sounds are encoded as a probabilistic measure of surprise. These results support the notion that auditory discrimination is driven by the development of brain networks for predictive processing, and can be measured in infants during sleep. The results presented here have implications for the interpretation of discrimination as a probabilistic process, and may provide a basis for the development of single-subject and single-trial classification in a clinically useful context. An infant's brain is processing information about the environment and performing computations, even during sleep. These computations reflect subtle differences in acoustic feature processing that are necessary for language-learning. Results from this study suggest that brain responses to deviant sounds in an oddball paradigm follow a cascade of oscillatory modulations. This cascade begins with a gamma response that later emerges as a beta synchronization, which is temporally coupled with a theta modulation, and followed by a second, subsequent theta modulation. The difference in frequency and timing of the theta modulations appears to reflect a measure of surprise. These insights into the neurophysiological mechanisms of auditory discrimination provide a basis for exploring the clinically utility of the MMR TF and other auditory oddball responses.

Sniffer patch laser uncaging response (SPLURgE): an assay of regional differences in allosteric receptor modulation and neurotransmitter clearance

PubMed Central

Christian, Catherine A.

2013-01-01

Allosteric modulators exert actions on neurotransmitter receptors by positively or negatively altering the effective response of these receptors to their respective neurotransmitter. γ-Aminobutyric acid (GABA) type A ionotropic receptors (GABAARs) are major targets for allosteric modulators such as benzodiazepines, neurosteroids, and barbiturates. Analysis of substances that produce similar effects has been hampered by the lack of techniques to assess the localization and function of such agents in brain slices. Here we describe measurement of the sniffer patch laser uncaging response (SPLURgE), which combines the sniffer patch recording configuration with laser photolysis of caged GABA. This methodology enables the detection of allosteric GABAAR modulators endogenously present in discrete areas of the brain slice and allows for the application of exogenous GABA with spatiotemporal control without altering the release and localization of endogenous modulators within the slice. Here we demonstrate the development and use of this technique for the measurement of allosteric modulation in different areas of the thalamus. Application of this technique will be useful in determining whether a lack of modulatory effect on a particular category of neurons or receptors is due to insensitivity to allosteric modulation or a lack of local release of endogenous ligand. We also demonstrate that this technique can be used to investigate GABA diffusion and uptake. This method thus provides a biosensor assay for rapid detection of endogenous GABAAR modulators and has the potential to aid studies of allosteric modulators that exert effects on other classes of neurotransmitter receptors, such as glutamate, acetylcholine, or glycine receptors. PMID:23843428

Sniffer patch laser uncaging response (SPLURgE): an assay of regional differences in allosteric receptor modulation and neurotransmitter clearance.

PubMed

Christian, Catherine A; Huguenard, John R

2013-10-01

Allosteric modulators exert actions on neurotransmitter receptors by positively or negatively altering the effective response of these receptors to their respective neurotransmitter. γ-Aminobutyric acid (GABA) type A ionotropic receptors (GABAARs) are major targets for allosteric modulators such as benzodiazepines, neurosteroids, and barbiturates. Analysis of substances that produce similar effects has been hampered by the lack of techniques to assess the localization and function of such agents in brain slices. Here we describe measurement of the sniffer patch laser uncaging response (SPLURgE), which combines the sniffer patch recording configuration with laser photolysis of caged GABA. This methodology enables the detection of allosteric GABAAR modulators endogenously present in discrete areas of the brain slice and allows for the application of exogenous GABA with spatiotemporal control without altering the release and localization of endogenous modulators within the slice. Here we demonstrate the development and use of this technique for the measurement of allosteric modulation in different areas of the thalamus. Application of this technique will be useful in determining whether a lack of modulatory effect on a particular category of neurons or receptors is due to insensitivity to allosteric modulation or a lack of local release of endogenous ligand. We also demonstrate that this technique can be used to investigate GABA diffusion and uptake. This method thus provides a biosensor assay for rapid detection of endogenous GABAAR modulators and has the potential to aid studies of allosteric modulators that exert effects on other classes of neurotransmitter receptors, such as glutamate, acetylcholine, or glycine receptors.

Auditory steady-state responses in cochlear implant users: Effect of modulation frequency and stimulation artifacts.

PubMed

Gransier, Robin; Deprez, Hanne; Hofmann, Michael; Moonen, Marc; van Wieringen, Astrid; Wouters, Jan

2016-05-01

Previous studies have shown that objective measures based on stimulation with low-rate pulse trains fail to predict the threshold levels of cochlear implant (CI) users for high-rate pulse trains, as used in clinical devices. Electrically evoked auditory steady-state responses (EASSRs) can be elicited by modulated high-rate pulse trains, and can potentially be used to objectively determine threshold levels of CI users. The responsiveness of the auditory pathway of profoundly hearing-impaired CI users to modulation frequencies is, however, not known. In the present study we investigated the responsiveness of the auditory pathway of CI users to a monopolar 500 pulses per second (pps) pulse train modulated between 1 and 100 Hz. EASSRs to forty-three modulation frequencies, elicited at the subject's maximum comfort level, were recorded by means of electroencephalography. Stimulation artifacts were removed by a linear interpolation between a pre- and post-stimulus sample (i.e., blanking). The phase delay across modulation frequencies was used to differentiate between the neural response and a possible residual stimulation artifact after blanking. Stimulation artifacts were longer than the inter-pulse interval of the 500pps pulse train for recording electrodes ipsilateral to the CI. As a result the stimulation artifacts could not be removed by artifact removal on the bases of linear interpolation for recording electrodes ipsilateral to the CI. However, artifact-free responses could be obtained in all subjects from recording electrodes contralateral to the CI, when subject specific reference electrodes (Cz or Fpz) were used. EASSRs to modulation frequencies within the 30-50 Hz range resulted in significant responses in all subjects. Only a small number of significant responses could be obtained, during a measurement period of 5 min, that originate from the brain stem (i.e., modulation frequencies in the 80-100 Hz range). This reduced synchronized activity of brain stem responses in long-term severely-hearing impaired CI users could be an attribute of processes associated with long-term hearing impairment and/or electrical stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Submillisecond unmasked subliminal visual stimuli evoke electrical brain responses.

PubMed

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

2015-04-01

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

Galantamine Facilitates Acquisition of a Trace-Conditioned Eyeblink Response in Healthy, Young Rabbits

ERIC Educational Resources Information Center

Simon, Barbara B.; Knuckley, Bryan; Powell, Donald A.

2004-01-01

Previous work has demonstrated that drugs increasing brain concentrations of acetylcholine can enhance cognition in aging and brain-damaged organisms. The present study assessed whether galantamine (GAL), an allosteric modulator of nicotinic cholinergic receptors and weak acetylcholinesterase inhibitor, could improve acquisition and retention of…

Sound envelope processing in the developing human brain: A MEG study.

PubMed

Tang, Huizhen; Brock, Jon; Johnson, Blake W

2016-02-01

This study investigated auditory cortical processing of linguistically-relevant temporal modulations in the developing brains of young children. Auditory envelope following responses to white noise amplitude modulated at rates of 1-80 Hz in healthy children (aged 3-5 years) and adults were recorded using a paediatric magnetoencephalography (MEG) system and a conventional MEG system, respectively. For children, there were envelope following responses to slow modulations but no significant responses to rates higher than about 25 Hz, whereas adults showed significant envelope following responses to almost the entire range of stimulus rates. Our results show that the auditory cortex of preschool-aged children has a sharply limited capacity to process rapid amplitude modulations in sounds, as compared to the auditory cortex of adults. These neurophysiological results are consistent with previous psychophysical evidence for a protracted maturational time course for auditory temporal processing. The findings are also in good agreement with current linguistic theories that posit a perceptual bias for low frequency temporal information in speech during language acquisition. These insights also have clinical relevance for our understanding of language disorders that are associated with difficulties in processing temporal information in speech. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

PubMed Central

Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

2013-01-01

Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

Modulation of Experimental Herpes Encephalitis-Associated Neurotoxicity through Sulforaphane Treatment

PubMed Central

Schachtele, Scott J.; Hu, Shuxian; Lokensgard, James R.

2012-01-01

Reactive oxygen species (ROS) produced by brain-infiltrating macrophages and neutrophils, as well as resident microglia, are pivotal to pathogen clearance during viral brain infection. However, unchecked free radical generation is also responsible for damage to and cytotoxicity of critical host tissue bystander to primary infection. These unwanted effects of excessive ROS are combated by local cellular production of antioxidant enzymes, including heme oxygenase-1 (HO-1) and glutathione peroxidase 1 (Gpx1). In this study, we showed that experimental murine herpes encephalitis triggered robust ROS production, as well as an opposing upregulation of the antioxidants HO-1 and Gpx1. This antioxidant response was insufficient to prevent tissue damage, neurotoxicity, and mortality associated with viral brain infection. Previous studies corroborate our data supporting astrocytes as the major antioxidant producer in brain cell cultures exposed to HSV-1 stimulated microglia. We hypothesized that stimulating opposing antioxidative responses in astrocytes, as well as neurons, would mitigate the effects of ROS-mediated neurotoxicity both in vitro and during viral brain infection in vivo. Here, we demonstrate that the addition of sulforaphane, a potent stimulator of antioxidant responses, enhanced HO-1 and Gpx1 expression in astrocytes through the activation of nuclear factor-E2-related factor 2 (Nrf2). Additionally, sulforaphane treatment was found to be effective in reducing neurotoxicity associated with HSV-stimulated microglial ROS production. Finally, intraperitoneal injections of sulforaphane into mice during active HSV infection reduced neuroinflammation via a decrease in brain-infiltrating leukocytes, macrophage- and neutrophil-produced ROS, and MHCII-positive, activated microglia. These data support a key role for astrocyte-produced antioxidants in modulating oxidative stress and neuronal damage in response to viral infection. PMID:22558388

Significant modulation of mitochondrial electron transport system by nicotine in various rat brain regions

USDA-ARS?s Scientific Manuscript database

The mitochondrion is the organelle responsible for generation of most usable energy in a cell. It also plays an important role in a series of physiological processes such as apoptosis and proliferation. Although previous studies have demonstrated that nicotine modulates the morphology and function ...

High-density EEG characterization of brain responses to auditory rhythmic stimuli during wakefulness and NREM sleep.

PubMed

Lustenberger, Caroline; Patel, Yogi A; Alagapan, Sankaraleengam; Page, Jessica M; Price, Betsy; Boyle, Michael R; Fröhlich, Flavio

2018-04-01

Auditory rhythmic sensory stimulation modulates brain oscillations by increasing phase-locking to the temporal structure of the stimuli and by increasing the power of specific frequency bands, resulting in Auditory Steady State Responses (ASSR). The ASSR is altered in different diseases of the central nervous system such as schizophrenia. However, in order to use the ASSR as biological markers for disease states, it needs to be understood how different vigilance states and underlying brain activity affect the ASSR. Here, we compared the effects of auditory rhythmic stimuli on EEG brain activity during wake and NREM sleep, investigated the influence of the presence of dominant sleep rhythms on the ASSR, and delineated the topographical distribution of these modulations. Participants (14 healthy males, 20-33 years) completed on the same day a 60 min nap session and two 30 min wakefulness sessions (before and after the nap). During these sessions, amplitude modulated (AM) white noise auditory stimuli at different frequencies were applied. High-density EEG was continuously recorded and time-frequency analyses were performed to assess ASSR during wakefulness and NREM periods. Our analysis revealed that depending on the electrode location, stimulation frequency applied and window/frequencies analysed the ASSR was significantly modulated by sleep pressure (before and after sleep), vigilance state (wake vs. NREM sleep), and the presence of slow wave activity and sleep spindles. Furthermore, AM stimuli increased spindle activity during NREM sleep but not during wakefulness. Thus, (1) electrode location, sleep history, vigilance state and ongoing brain activity needs to be carefully considered when investigating ASSR and (2) auditory rhythmic stimuli during sleep might represent a powerful tool to boost sleep spindles. Copyright © 2017 Elsevier Inc. All rights reserved.

Diffusion of responsibility attenuates altruistic punishment: A functional magnetic resonance imaging effective connectivity study.

PubMed

Feng, Chunliang; Deshpande, Gopikrishna; Liu, Chao; Gu, Ruolei; Luo, Yue-Jia; Krueger, Frank

2016-02-01

Humans altruistically punish violators of social norms to enforce cooperation and pro-social behaviors. However, such altruistic behaviors diminish when others are present, due to a diffusion of responsibility. We investigated the neural signatures underlying the modulations of diffusion of responsibility on altruistic punishment, conjoining a third-party punishment task with event-related functional magnetic resonance imaging and multivariate Granger causality mapping. In our study, participants acted as impartial third-party decision-makers and decided how to punish norm violations under two different social contexts: alone (i.e., full responsibility) or in the presence of putative other third-party decision makers (i.e., diffused responsibility). Our behavioral results demonstrated that the diffusion of responsibility served as a mediator of context-dependent punishment. In the presence of putative others, participants who felt less responsible also punished less severely in response to norm violations. Our neural results revealed that underlying this behavioral effect was a network of interconnected brain regions. For unfair relative to fair splits, the presence of others led to attenuated responses in brain regions implicated in signaling norm violations (e.g., AI) and to increased responses in brain regions implicated in calculating values of norm violations (e.g., vmPFC, precuneus) and mentalizing about others (dmPFC). The dmPFC acted as the driver of the punishment network, modulating target regions, such as AI, vmPFC, and precuneus, to adjust altruistic punishment behavior. Our results uncovered the neural basis of the influence of diffusion of responsibility on altruistic punishment and highlighted the role of the mentalizing network in this important phenomenon. Hum Brain Mapp 37:663-677, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Aquaporins: important but elusive drug targets

PubMed Central

Verkman, Alan S.; Anderson, Marc O.; Papadopoulos, Marios C.

2014-01-01

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators. PMID:24625825

Processing of emotional words measured simultaneously with steady-state visually evoked potentials and near-infrared diffusing-wave spectroscopy.

PubMed

Koban, Leonie; Ninck, Markus; Li, Jun; Gisler, Thomas; Kissler, Johanna

2010-07-27

Emotional stimuli are preferentially processed compared to neutral ones. Measuring the magnetic resonance blood-oxygen level dependent (BOLD) response or EEG event-related potentials, this has also been demonstrated for emotional versus neutral words. However, it is currently unclear whether emotion effects in word processing can also be detected with other measures such as EEG steady-state visual evoked potentials (SSVEPs) or optical brain imaging techniques. In the present study, we simultaneously performed SSVEP measurements and near-infrared diffusing-wave spectroscopy (DWS), a new optical technique for the non-invasive measurement of brain function, to measure brain responses to neutral, pleasant, and unpleasant nouns flickering at a frequency of 7.5 Hz. The power of the SSVEP signal was significantly modulated by the words' emotional content at occipital electrodes, showing reduced SSVEP power during stimulation with pleasant compared to neutral nouns. By contrast, the DWS signal measured over the visual cortex showed significant differences between stimulation with flickering words and baseline periods, but no modulation in response to the words' emotional significance. This study is the first investigation of brain responses to emotional words using simultaneous measurements of SSVEPs and DWS. Emotional modulation of word processing was detected with EEG SSVEPs, but not by DWS. SSVEP power for emotional, specifically pleasant, compared to neutral words was reduced, which contrasts with previous results obtained when presenting emotional pictures. This appears to reflect processing differences between symbolic and pictorial emotional stimuli. While pictures prompt sustained perceptual processing, decoding the significance of emotional words requires more internal associative processing. Reasons for an absence of emotion effects in the DWS signal are discussed.

Global signal modulation of single-trial fMRI response variability: Effect on positive vs negative BOLD response relationship.

PubMed

Mayhew, S D; Mullinger, K J; Ostwald, D; Porcaro, C; Bowtell, R; Bagshaw, A P; Francis, S T

2016-06-01

In functional magnetic resonance imaging (fMRI), the relationship between positive BOLD responses (PBRs) and negative BOLD responses (NBRs) to stimulation is potentially informative about the balance of excitatory and inhibitory brain responses in sensory cortex. In this study, we performed three separate experiments delivering visual, motor or somatosensory stimulation unilaterally, to one side of the sensory field, to induce PBR and NBR in opposite brain hemispheres. We then assessed the relationship between the evoked amplitudes of contralateral PBR and ipsilateral NBR at the level of both single-trial and average responses. We measure single-trial PBR and NBR peak amplitudes from individual time-courses, and show that they were positively correlated in all experiments. In contrast, in the average response across trials the absolute magnitudes of both PBR and NBR increased with increasing stimulus intensity, resulting in a negative correlation between mean response amplitudes. Subsequent analysis showed that the amplitude of single-trial PBR was positively correlated with the BOLD response across all grey-matter voxels and was not specifically related to the ipsilateral sensory cortical response. We demonstrate that the global component of this single-trial response modulation could be fully explained by voxel-wise vascular reactivity, the BOLD signal standard deviation measured in a separate resting-state scan (resting state fluctuation amplitude, RSFA). However, bilateral positive correlation between PBR and NBR regions remained. We further report that modulations in the global brain fMRI signal cannot fully account for this positive PBR-NBR coupling and conclude that the local sensory network response reflects a combination of superimposed vascular and neuronal signals. More detailed quantification of physiological and noise contributions to the BOLD signal is required to fully understand the trial-by-trial PBR and NBR relationship compared with that of average responses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Frequency-dependent tACS modulation of BOLD signal during rhythmic visual stimulation.

PubMed

Chai, Yuhui; Sheng, Jingwei; Bandettini, Peter A; Gao, Jia-Hong

2018-05-01

Transcranial alternating current stimulation (tACS) has emerged as a promising tool for modulating cortical oscillations. In previous electroencephalogram (EEG) studies, tACS has been found to modulate brain oscillatory activity in a frequency-specific manner. However, the spatial distribution and hemodynamic response for this modulation remains poorly understood. Functional magnetic resonance imaging (fMRI) has the advantage of measuring neuronal activity in regions not only below the tACS electrodes but also across the whole brain with high spatial resolution. Here, we measured fMRI signal while applying tACS to modulate rhythmic visual activity. During fMRI acquisition, tACS at different frequencies (4, 8, 16, and 32 Hz) was applied along with visual flicker stimulation at 8 and 16 Hz. We analyzed the blood-oxygen-level-dependent (BOLD) signal difference between tACS-ON vs tACS-OFF, and different frequency combinations (e.g., 4 Hz tACS, 8 Hz flicker vs 8 Hz tACS, 8 Hz flicker). We observed significant tACS modulation effects on BOLD responses when the tACS frequency matched the visual flicker frequency or the second harmonic frequency. The main effects were predominantly seen in regions that were activated by the visual task and targeted by the tACS current distribution. These findings bridge different scientific domains of tACS research and demonstrate that fMRI could localize the tACS effect on stimulus-induced brain rhythms, which could lead to a new approach for understanding the high-level cognitive process shaped by the ongoing oscillatory signal. © 2018 Wiley Periodicals, Inc.

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

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

Michaelides, M.; Wang, G.; Michaelides, M.

Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated imagemore » registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.« less

Aroused with heart: Modulation of heartbeat evoked potential by arousal induction and its oscillatory correlates

PubMed Central

Luft, Caroline Di Bernardi; Bhattacharya, Joydeep

2015-01-01

Recent studies showed that the visceral information is constantly processed by the brain, thereby potentially influencing cognition. One index of such process is the heartbeat evoked potential (HEP), an ERP component related to the cortical processing of the heartbeat. The HEP is sensitive to a number of factors such as motivation, attention, pain, which are associated with higher levels of arousal. However, the role of arousal and its associated brain oscillations on the HEP has not been characterized, yet it could underlie the previous findings. Here we analysed the effects of high- (HA) and low-arousal (LA) induction on the HEP. Further, we investigated the brain oscillations and their role in the HEP in response to HA and LA inductions. As compared to LA, HA was associated with a higher HEP and lower alpha oscillations. Interestingly, individual differences in the HEP modulation by arousal induction were correlated with alpha oscillations. In particular, participants with higher alpha power during the arousal inductions showed a larger HEP in response to HA compared to LA. In summary, we demonstrated that arousal induction affects the cortical processing of heartbeats; and that the alpha oscillations may modulate this effect. PMID:26503014

Radiation-induced inflammatory markers of brain injury are modulated by PPARdelta activation in vitro and in vivo

NASA Astrophysics Data System (ADS)

Schnegg, Caroline Isabel

As a result of improvements in cancer therapy and health care, the population of long-term cancer survivors is growing. For these approximately 12 million long-term cancer survivors, brain metastases are a significant risk. Fractionated partial or whole-brain irradiation (fWBI) is often required to treat both primary and metastatic brain cancer. Radiation-induced normal tissue injury, including progressive cognitive impairment, however, can significantly affect the well-being of the approximately 200,000 patients who receive these treatments each year. Recent reports indicate that radiation-induced brain injury is associated with chronic inflammatory and oxidative stress responses, as well as increased microglial activation in the brain. Anti-inflammatory drugs may, therefore, be a beneficial therapy to mitigate radiation-induced brain injury. We hypothesized that activation of peroxisomal proliferator activated receptor delta (PPARō) would prevent or ameliorate radiation-induced brain injury, including cognitive impairment, in part, by alleviating inflammatory responses in microglia. For our in vitro studies, we hypothesized that PPARō activation would prevent the radiation-induced inflammatory response in microglia following irradiation. Incubating BV-2 murine microglial cells with the (PPAR)ō agonist, L-165041, prevented the radiation-induced increase in: i) intracellular ROS generation, ii) Cox-2 and MCP-1 expression, and iii) IL-1β and TNF-α message levels. This occured, in part, through PPARō-mediated modulation of stress activated kinases and proinflammatory transcription factors. PPARō inhibited NF-κB via transrepression by physically interacting with the p65 subunit, and prevented activation of the PKCα/MEK1/2/ERK1/2/AP-1 pathway by inhibiting the radiation-induced increase in intracellular ROS generation. These data support the hypothesis that PPARō activation can modulate the radiation-induced oxidative stress and inflammatory responses in microglia in vitro. To extend our in vitro findings in vivo, we investigated whether administration of the peroxisomal proliferator-activated receptor (PPAR)ä agonist, GW0742, prevented radiation-induced brain injury in C57Bl/6 WT mice. Our data demonstrate that GW0742 prevented the radiation-induced increase in the number of activated microglia (CD68+ cells) in wild-type (WT) mice 1 week following 10 Gy WBI. Furthermore, GW0742 inhibited the WBI-induced increase in IL-1β message levels and ERK phosphorylation observed 3 h post-irradiation. In contrast, GW0742 administration failed to modulate the radiation-induced decrease in hippocampal neurogenesis (NeuN+/BrdU+ cells) determined 2 months after irradiation, or mitigate hippocampal-dependent spatial memory impairment observed 3 months post-irradiation using the Barnes Maze task. We used PPARō knockout (KO) mice to examine if the effects of GW0742 are PPARō-dependent. Unexpectedly, PPARō KO mice exhibited a differential response following WBI compared to WT mice; therefore, we were unable to make mechanistic conclusions about GW0742. KO mice do not exhibit a WBI-induced increase in activated microglia; however, they appeared to display a pronounced astrocytic response. In particular, PPARō KO but not WT mice displayed increased GFAP message levels 2 months after WBI. Additionally, the number of GFAP+ cells was reduced significantly in the WT mice 2 months after WBI, but it was not in the PPARō KO mice. These results demonstrate that: i) GW0742 prevents the radiation-induced increase in microglial activation and inflammatory markers, and ii) WT and PPARō KO mice have a differential response to WBI.

The Analysis for Activations in the Brain during Hearing the Amplitude-Modulated Tone by fMRI Measurement

NASA Astrophysics Data System (ADS)

Fukami, Tadanori; Shimada, Takamasa; Akatsuka, Takao; Saito, Yoichi

In audiometry, ABR (Auditory Brainstem Response) is widely used. However, it shows low accuracy in low frequency band. Meanwhile, AMFR (Amplitude-Modulation-Following Response), the response during hearing an amplitude-modulated tone, has high frequency specificity and is brought to attention. As the first step to clinical application of AMFR, we investigated the activated areas in a brain when the subjects hear SAM tone (Sinusoidally Amplitude-Modulated tone) with both ears. We measured following two signals. One is the difference of BOLD (Blood Oxygenation Level Dependent) signal between hearing SAM tone vs. silence, the other is the difference of BOLD signal between hearing SAM tone vs. unmodulated tone. As a result, in the case of SAM vs. silence, the bilaterally auditory cortex (Broadmann Area 41, 42), the biratelally BA 10, left superior frontal gyrus and right superior temporal gyrus were activated (p<0.0037, uncorrected). In the case of SAM vs. unmodulated tone, the bilaterally superior frontal gyrus (BA 6) and precuneus (BA 7), neighboring area including the bilaterally inferior parietal lobule (BA 40), the bilaterally medial frontal gyrus and superior frontal gyrus were activated (p<0.021, uncorrected). Activations of visual perception due to eye-opened state were detected in some parts of activations. As a result, we inferred that modulated tone was recognized in the medial frontal gyrus and inferior parietal lobule was the part related to perception of amplitude-modulation.

Glutamate Excitoxicity Is the Key Molecular Mechanism Which Is Influenced by Body Temperature during the Acute Phase of Brain Stroke

PubMed Central

Campos, Francisco; Pérez-Mato, María; Agulla, Jesús; Blanco, Miguel; Barral, David; Almeida, Ángeles; Brea, David; Waeber, Christian; Castillo, José; Ramos-Cabrer, Pedro

2012-01-01

Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke. PMID:22952923

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

PubMed

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

2012-01-01

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

Glutamate excitoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

PubMed

Campos, Francisco; Pérez-Mato, María; Agulla, Jesús; Blanco, Miguel; Barral, David; Almeida, Angeles; Brea, David; Waeber, Christian; Castillo, José; Ramos-Cabrer, Pedro

2012-01-01

Glutamate excitotoxicity, metabolic rate and inflammatory response have been associated to the deleterious effects of temperature during the acute phase of stroke. So far, the association of temperature with these mechanisms has been studied individually. However, the simultaneous study of the influence of temperature on these mechanisms is necessary to clarify their contributions to temperature-mediated ischemic damage. We used non-invasive Magnetic Resonance Spectroscopy to simultaneously measure temperature, glutamate excitotoxicity and metabolic rate in the brain in animal models of ischemia. The immune response to ischemia was measured through molecular serum markers in peripheral blood. We submitted groups of animals to different experimental conditions (hypothermia at 33°C, normothermia at 37°C and hyperthermia at 39°C), and combined these conditions with pharmacological modulation of glutamate levels in the brain through systemic injections of glutamate and oxaloacetate. We show that pharmacological modulation of glutamate levels can neutralize the deleterious effects of hyperthermia and the beneficial effects of hypothermia, however the analysis of the inflammatory response and metabolic rate, demonstrated that their effects on ischemic damage are less critical than glutamate excitotoxity. We conclude that glutamate excitotoxicity is the key molecular mechanism which is influenced by body temperature during the acute phase of brain stroke.

Social inclusion enhances biological motion processing: A functional near-infrared spectroscopy study

PubMed Central

Bolling, Danielle Z.; Pelphrey, Kevin A.; Kaiser, Martha D.

2012-01-01

Humans are especially tuned to the movements of other people. Neural correlates of this social attunement have been proposed to lie in and around the right posterior superior temporal sulcus (STS) region, which robustly responds to biological motion in contrast to a variety of non-biological motions. This response persists even when no form information is provided, as in point-light displays (PLDs). The aim of the current study was to assess the ability of functional near-infrared spectroscopy (fNIRS) to reliably measure brain responses to PLDs of biological motion, and determine the sensitivity of these responses to interpersonal contextual factors. To establish reliability, we measured brain activation to biological motion with fNIRS and functional magnetic resonance imaging (fMRI) during two separate sessions in an identical group of 12 participants. To establish sensitivity, brain responses to biological motion measured with fNIRS were subjected to an additional social manipulation where participants were either socially included or excluded before viewing PLDs of biological motion. Results revealed comparable brain responses to biological motion using fMRI and fNIRS in the right supramarginal gyrus. Further, social inclusion increased brain responses to biological motion in right supramarginal gyrus and posterior STS. Thus, fNIRS can reliably measure brain responses to biological motion and can detect social experience-dependent modulations of these brain responses. PMID:22941501

A gut (microbiome) feeling about the brain.

PubMed

Sherwin, Eoin; Rea, Kieran; Dinan, Timothy G; Cryan, John F

2016-03-01

There is an increasing realization that the microorganisms which reside within our gut form part of a complex multidirectional communication network with the brain known as the microbiome-gut-brain axis. In this review, we focus on recent findings which support a role for this axis in modulating neurodevelopment and behavior. A growing body of research is uncovering that under homeostatic conditions and in response to internal and external stressors, the bacterial commensals of our gut can signal to the brain through a variety of mechanisms to influence processes such neurotransmission, neurogenesis, microglia activation, and modulate behavior. Moreover, the mechanisms underlying the ability of stress to modulate the microbiota and also for microbiota to change the set point for stress sensitivity are being unraveled. Dysregulation of the gut microbiota composition has been identified in a number of psychiatric disorders, including depression. This has led to the concept of bacteria that have a beneficial effect upon behavior and mood (psychobiotics) being proposed for potential therapeutic interventions. Understanding the mechanisms by which the bacterial commensals of our gut are involved in brain function may lead to the development of novel microbiome-based therapies for these mood and behavioral disorders.

Bodily ownership modulation in defensive responses: physiological evidence in brain-damaged patients with pathological embodiment of other's body parts.

PubMed

Fossataro, C; Gindri, P; Mezzanato, T; Pia, L; Garbarini, F

2016-06-13

Do conscious beliefs about the body affect defensive mechanisms within the body? To answer this question we took advantage from a monothematic delusion of bodily ownership, in which brain-damaged patients misidentify alien limbs as their own. We investigated whether the delusional belief that an alien hand is their own hand modulates a subcortical defensive response, such as the hand-blink reflex. The blink, dramatically increases when the threated hand is inside the defensive peripersonal-space of the face. In our between-subjects design, including patients and controls, the threat was brought near the face either by the own hand or by another person's hand. Our results show an ownership-dependent modulation of the defensive response. In controls, as well as in the patients' intact-side, the response enhancement is significantly greater when the threat was brought near the face by the own than by the alien hand. Crucially, in the patients' affected-side (where the pathological embodiment occurs), the alien (embodied) hand elicited a response enhancement comparable to that found when the threat is brought near the face by the real hand. These findings suggest the existence of a mutual interaction between our conscious beliefs about the body and the physiological mechanisms within the body.

Credit Assignment in Multiple Goal Embodied Visuomotor Behavior

PubMed Central

Rothkopf, Constantin A.; Ballard, Dana H.

2010-01-01

The intrinsic complexity of the brain can lead one to set aside issues related to its relationships with the body, but the field of embodied cognition emphasizes that understanding brain function at the system level requires one to address the role of the brain-body interface. It has only recently been appreciated that this interface performs huge amounts of computation that does not have to be repeated by the brain, and thus affords the brain great simplifications in its representations. In effect the brain's abstract states can refer to coded representations of the world created by the body. But even if the brain can communicate with the world through abstractions, the severe speed limitations in its neural circuitry mean that vast amounts of indexing must be performed during development so that appropriate behavioral responses can be rapidly accessed. One way this could happen would be if the brain used a decomposition whereby behavioral primitives could be quickly accessed and combined. This realization motivates our study of independent sensorimotor task solvers, which we call modules, in directing behavior. The issue we focus on herein is how an embodied agent can learn to calibrate such individual visuomotor modules while pursuing multiple goals. The biologically plausible standard for module programming is that of reinforcement given during exploration of the environment. However this formulation contains a substantial issue when sensorimotor modules are used in combination: The credit for their overall performance must be divided amongst them. We show that this problem can be solved and that diverse task combinations are beneficial in learning and not a complication, as usually assumed. Our simulations show that fast algorithms are available that allot credit correctly and are insensitive to measurement noise. PMID:21833235

Retrieval Search and Strength Evoke Dissociable Brain Activity during Episodic Memory Recall

PubMed Central

Reas, Emilie T.; Brewer, James B.

2014-01-01

Neuroimaging studies of episodic memory retrieval have revealed activations in the human frontal, parietal, and medial-temporal lobes that are associated with memory strength. However, it remains unclear whether these brain responses are veritable signals of memory strength or are instead regulated by concomitant subcomponents of retrieval such as retrieval effort or mental search. This study used event-related fMRI during cued recall of previously memorized word-pair associates to dissociate brain responses modulated by memory search from those modulated by the strength of a recalled memory. Search-related deactivations, dissociated from activity due to memory strength, were observed in regions of the default network, whereas distinctly strength-dependent activations were present in superior and inferior parietal and dorsolateral PFC. Both search and strength regulated activity in dorsal anterior cingulate and anterior insula. These findings suggest that, although highly correlated and partially subserved by overlapping cognitive control mechanisms, search and memory strength engage dissociable regions of frontoparietal attention and default networks. PMID:23190328

Neural Representation of Subjective Sexual Arousal in Men and Women.

PubMed

Parada, Mayte; Gérard, Marina; Larcher, Kevin; Dagher, Alain; Binik, Yitzchak M

2016-10-01

Studies investigating brain indices of sexual arousal have begun to elucidate the brain's role in processing subjective arousal; however, most research has focused on men, used discrete ratings of subjective arousal, and used stimuli too short to induce significant arousal in women. To examine brain regions modulated by changes in subjective sexual arousal (SSA) rating intensity in men and women. Two groups (20 men, 20 women) viewed movie clips (erotic or humorous) while continuously evaluating changes in their SSA using a Likert-like scale (0 = not aroused, 10 = most aroused) and answering discrete questions about liking the movies and wanting sexual stimulation. Brain activity was measured using functional magnetic resonance imaging. Blood oxygen level-dependent responses and continuous and discrete measurements of sexual arousal. Erotic movies induced significant SSA in men and women. No sex difference in mean SSA was found in response to the erotic movies on continuous or discrete measurements. Several brain regions were correlated with changes in SSA. Parametric modulation with rating intensity showed a specific group of regions within the parietal lobe that showed significant differences in activity among low, medium, and high SSA. Multiple regions were concordant with changes in SSA; however, a subset of regions in men and women was modulated by SSA intensity, a subset previously linked to attentional processes, monitoring of internal body representation, and processing of sensory information from the genitals. This study highlights that similar brain regions are activated during subjective assessment of sexual arousal in men and women. The data further highlight the fact that SSA is a complex phenomenon made up of multiple interoceptive and attentional processes. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Enhancing Motor Network Activity Using Real-Time Functional MRI Neurofeedback of Left Premotor Cortex

PubMed Central

Marins, Theo F.; Rodrigues, Erika C.; Engel, Annerose; Hoefle, Sebastian; Basílio, Rodrigo; Lent, Roberto; Moll, Jorge; Tovar-Moll, Fernanda

2015-01-01

Neurofeedback by functional magnetic resonance imaging (fMRI) is a technique of potential therapeutic relevance that allows individuals to be aware of their own neurophysiological responses and to voluntarily modulate the activity of specific brain regions, such as the premotor cortex (PMC), important for motor recovery after brain injury. We investigated (i) whether healthy human volunteers are able to up-regulate the activity of the left PMC during a right hand finger tapping motor imagery (MI) task while receiving continuous fMRI-neurofeedback, and (ii) whether successful modulation of brain activity influenced non-targeted motor control regions. During the MI task, participants of the neurofeedback group (NFB) received ongoing visual feedback representing the level of fMRI responses within their left PMC. Control (CTL) group participants were shown similar visual stimuli, but these were non-contingent on brain activity. Both groups showed equivalent levels of behavioral ratings on arousal and MI, before and during the fMRI protocol. In the NFB, but not in CLT group, brain activation during the last run compared to the first run revealed increased activation in the left PMC. In addition, the NFB group showed increased activation in motor control regions extending beyond the left PMC target area, including the supplementary motor area, basal ganglia and cerebellum. Moreover, in the last run, the NFB group showed stronger activation in the left PMC/inferior frontal gyrus when compared to the CTL group. Our results indicate that modulation of PMC and associated motor control areas can be achieved during a single neurofeedback-fMRI session. These results contribute to a better understanding of the underlying mechanisms of MI-based neurofeedback training, with direct implications for rehabilitation strategies in severe brain disorders, such as stroke. PMID:26733832

Locomotor activity modulates associative learning in mouse cerebellum.

PubMed

Albergaria, Catarina; Silva, N Tatiana; Pritchett, Dominique L; Carey, Megan R

2018-05-01

Changes in behavioral state can profoundly influence brain function. Here we show that behavioral state modulates performance in delay eyeblink conditioning, a cerebellum-dependent form of associative learning. Increased locomotor speed in head-fixed mice drove earlier onset of learning and trial-by-trial enhancement of learned responses that were dissociable from changes in arousal and independent of sensory modality. Eyelid responses evoked by optogenetic stimulation of mossy fiber inputs to the cerebellum, but not at sites downstream, were positively modulated by ongoing locomotion. Substituting prolonged, low-intensity optogenetic mossy fiber stimulation for locomotion was sufficient to enhance conditioned responses. Our results suggest that locomotor activity modulates delay eyeblink conditioning through increased activation of the mossy fiber pathway within the cerebellum. Taken together, these results provide evidence for a novel role for behavioral state modulation in associative learning and suggest a potential mechanism through which engaging in movement can improve an individual's ability to learn.

Effects of gamma-aminobutyric acid-modulating drugs on working memory and brain function in patients with schizophrenia.

PubMed

Menzies, Lara; Ooi, Cinly; Kamath, Shri; Suckling, John; McKenna, Peter; Fletcher, Paul; Bullmore, Ed; Stephenson, Caroline

2007-02-01

Cognitive impairment causes morbidity in schizophrenia and could be due to abnormalities of cortical interneurons using the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). To test the predictions that cognitive and brain functional responses to GABA-modulating drugs are correlated and abnormal in schizophrenia. Pharmacological functional magnetic resonance imaging study of 2 groups, each undergoing scanning 3 times, using an N-back working memory task, after placebo, lorazepam, or flumazenil administration. Eleven patients with chronic schizophrenia were recruited from a rehabilitation service, and 11 healthy volunteers matched for age, sex, and premorbid IQ were recruited from the local community. Intervention Participants received 2 mg of oral lorazepam, a 0.9-mg intravenous flumazenil bolus followed by a flumazenil infusion of 0.0102 mg/min, or oral and intravenous placebo. Working memory performance was summarized by the target discrimination index at several levels of difficulty. Increasing (or decreasing) brain functional activation in response to increasing task difficulty was summarized by the positive (or negative) load response. Lorazepam impaired performance and flumazenil enhanced it; these cognitive effects were more salient in schizophrenic patients. Functional magnetic resonance imaging demonstrated positive load response in a frontoparietal system and negative load response in the temporal and posterior cingulate regions; activation of the frontoparietal cortex was positively correlated with deactivation of the temporocingulate cortex. After placebo administration, schizophrenic patients had abnormally attenuated activation of the frontoparietal cortex and deactivation of the temporocingulate cortex; this pattern was mimicked in healthy volunteers and exacerbated in schizophrenic patients by lorazepam. However, in schizophrenic patients, flumazenil enhanced deactivation of the temporocingulate and activation of the anterior cingulate cortices. The GABA-modulating drugs differentially affect working memory performance and brain function in schizophrenia. Cognitive impairment in schizophrenia may reflect abnormal inhibitory function and could be treated by drugs targeting GABA neurotransmission.

Hypnotic analgesia reduces brain responses to pain seen in others.

PubMed

Braboszcz, Claire; Brandao-Farinelli, Edith; Vuilleumier, Patrik

2017-08-29

Brain responses to pain experienced by oneself or seen in other people show consistent overlap in the pain processing network, particularly anterior insula, supporting the view that pain empathy partly relies on neural processes engaged by self-nociception. However, it remains unresolved whether changes in one's own pain sensation may affect empathic responding to others' pain. Here we show that inducing analgesia through hypnosis leads to decreased responses to both self and vicarious experience of pain. Activations in the right anterior insula and amygdala were markedly reduced when participants received painful thermal stimuli following hypnotic analgesia on their own hand, but also when they viewed pictures of others' hand in pain. Functional connectivity analysis indicated that this hypnotic modulation of pain responses was associated with differential recruitment of right prefrontal regions implicated in selective attention and inhibitory control. Our results provide novel support to the view that self-nociception is involved during empathy for pain, and demonstrate the possibility to use hypnotic procedures to modulate higher-level emotional and social processes.

Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts

PubMed Central

Gambino, Giuditta; Allegra, Mario; Sardo, Pierangelo; Attanzio, Alessandro; Tesoriere, Luisa; Livrea, Maria A.; Ferraro, Giuseppe; Carletti, Fabio

2018-01-01

Several studies have recently investigated the role of nutraceuticals in complex pathophysiological processes such as oxidative damages, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal cells, such as excitability, are still poorly investigated. For this reason, the possible modulation of neuronal excitability by phytochemicals (PhC) could represent an interesting field of research given that excitotoxicity phenomena are involved in neurodegenerative alterations leading, for example, to Alzheimer’s disease. The present study was focused on indicaxanthin from Opuntia ficus indica, a bioactive betalain pigment, with a proven antioxidant and anti-inflammatory potential, previously found to cross blood-brain barrier (BBB) and to modulate the bioelectric activity of hippocampal neurons. On this basis, we aimed at detecting the specific brain areas where indicaxanthin localizes after oral administration at dietary-achievable amounts and highlighting eventual local effects on the excitability of single neuronal units. HPLC analysis of brain tissue 1 h after ingestion of 2 μmol/kg indicaxanthin indicated that the phytochemical accumulates in cortex, hippocampus, diencephalon, brainstem and cerebellum, but not in the striato-pallidal complex. Then, electrophysiological recordings, applying the microiontophoretic technique, were carried out with different amounts of indicaxanthin (0.34, 0.17, 0.085 ng/neuron) to assess whether indicaxanthin influenced the neuronal firing rate. The data showed that the bioelectric activity of neurons belonging to different brain areas was modulated after local injection of indicaxanthin, mainly with dose-related responses. A predominating inhibitory effect was observed, suggesting a possible novel beneficial effect of indicaxanthin in reducing cell excitability. These findings can constitute a new rationale for exploring biological mechanisms through which PhC could modulate neuronal function with a relapse on complex cognitive brain process and related neurodegenerative conditions. PMID:29867444

Brain mediators of predictive cue effects on perceived pain

PubMed Central

Atlas, Lauren Y.; Bolger, Niall; Lindquist, Martin A.; Wager, Tor D.

2010-01-01

Information about upcoming pain strongly influences pain experience in experimental and clinical settings, but little is known about the brain mechanisms that link expectation and experience. To identify the pathways by which informational cues influence perception, analyses must jointly consider both the effects of cues on brain responses and the relationship between brain responses and changes in reported experience. Our task and analysis strategy were designed to test these relationships. Auditory cues elicited expectations for low or high painful thermal stimulation, and we assessed how cues influenced human subjects’ pain reports and BOLD fMRI responses to matched levels of noxious heat. We used multi-level mediation analysis to identify brain regions that 1) are modulated by predictive cues, 2) predict trial-to-trial variations in pain reports, and 3) formally mediate the relationship between cues and reported pain. Cues influenced heat-evoked responses in most canonical pain-processing regions, including both medial and lateral pain pathways. Effects on several regions correlated with pre-task expectations, suggesting that expectancy plays a prominent role. A subset of pain-processing regions, including anterior cingulate cortex, anterior insula, and thalamus, formally mediated cue effects on pain. Effects on these regions were in turn mediated by cue-evoked anticipatory activity in the medial orbitofrontal cortex (OFC) and ventral striatum, areas not previously directly implicated in nociception. These results suggest that activity in pain-processing regions reflects a combination of nociceptive input and top-down information related to expectations, and that anticipatory processes in OFC and striatum may play a key role in modulating pain processing. PMID:20881115

Transcranial amelioration of inflammation and cell death after brain injury

NASA Astrophysics Data System (ADS)

Roth, Theodore L.; Nayak, Debasis; Atanasijevic, Tatjana; Koretsky, Alan P.; Latour, Lawrence L.; McGavern, Dorian B.

2014-01-01

Traumatic brain injury (TBI) is increasingly appreciated to be highly prevalent and deleterious to neurological function. At present, no effective treatment options are available, and little is known about the complex cellular response to TBI during its acute phase. To gain insights into TBI pathogenesis, we developed a novel murine closed-skull brain injury model that mirrors some pathological features associated with mild TBI in humans and used long-term intravital microscopy to study the dynamics of the injury response from its inception. Here we demonstrate that acute brain injury induces vascular damage, meningeal cell death, and the generation of reactive oxygen species (ROS) that ultimately breach the glial limitans and promote spread of the injury into the parenchyma. In response, the brain elicits a neuroprotective, purinergic-receptor-dependent inflammatory response characterized by meningeal neutrophil swarming and microglial reconstitution of the damaged glial limitans. We also show that the skull bone is permeable to small-molecular-weight compounds, and use this delivery route to modulate inflammation and therapeutically ameliorate brain injury through transcranial administration of the ROS scavenger, glutathione. Our results shed light on the acute cellular response to TBI and provide a means to locally deliver therapeutic compounds to the site of injury.

Activation of raphe nuclei triggers rapid and distinct effects on parallel olfactory bulb output channels

PubMed Central

Kapoor, Vikrant; Provost, Allison; Agarwal, Prateek; Murthy, Venkatesh N.

2015-01-01

The serotonergic raphe nuclei are involved in regulating brain states over time-scales of minutes and hours. We examined more rapid effects of serotonergic activation on two classes of principal neurons in the mouse olfactory bulb, mitral and tufted cells, which send olfactory information to distinct targets. Brief stimulation of the raphe nuclei led to excitation of tufted cells at rest and potentiation of their odor responses. While mitral cells at rest were also excited by raphe activation, their odor responses were bidirectionally modulated, leading to improved pattern separation of odors. In vitro whole-cell recordings revealed that specific optogenetic activation of raphe axons affected bulbar neurons through dual release of serotonin and glutamate. Therefore, the raphe nuclei, in addition to their role in neuromodulation of brain states, are also involved in fast, sub-second top-down modulation, similar to cortical feedback. This modulation can selectively and differentially sensitize or decorrelate distinct output channels. PMID:26752161

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.

Apelin targets gut contraction to control glucose metabolism via the brain

PubMed Central

Fournel, Audren; Drougard, Anne; Duparc, Thibaut; Marlin, Alysson; Brierley, Stuart M; Castro, Joel; Le-Gonidec, Sophie; Masri, Bernard; Colom, André; Lucas, Alexandre; Rousset, Perrine; Cenac, Nicolas; Vergnolle, Nathalie; Valet, Philippe; Cani, Patrice D; Knauf, Claude

2017-01-01

Objective The gut–brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus. Design We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose. Results In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle. Conclusions Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders. PMID:26565000

Lifestyle Shapes the Dialogue between Environment, Microglia, and Adult Neurogenesis.

PubMed

Valero, Jorge; Paris, Iñaki; Sierra, Amanda

2016-04-20

Lifestyle modulates brain function. Diet, stress levels, and physical exercise among other factors influence the "brain cognitive reserve", that is, the capacity of the brain to maintain a normal function when confronting neurodegenerative diseases, injury, and/or aging. This cognitive reserve relays on several cellular and molecular elements that contribute to brain plasticity allowing adaptive responses to cognitive demands, and one of its key components is the hippocampal neurogenic reserve. Hippocampal neural stem cells give rise to new neurons that integrate into the local circuitry and contribute to hippocampal functions such as memory and learning. Importantly, adult hippocampal neurogenesis is well-known to be modulated by the demands of the environment and lifestyle factors. Diet, stress, and physical exercise directly act on neural stem cells and/or their progeny, but, in addition, they may also indirectly affect neurogenesis by acting on microglia. Microglia, the guardians of the brain, rapidly sense changes in the brain milieu, and it has been recently shown that their function is affected by lifestyle factors. However, few studies have analyzed the modulatory effect of microglia on adult neurogenesis in these conditions. Here, we review the current knowledge about the dialogue maintained between microglia and the hippocampal neurogenic cascade. Understanding how the communication between microglia and hippocampal neurogenesis is affected by lifestyle choices is crucial to maintain the brain cognitive reserve and prevent the maladaptive responses that emerge during disease or injury through adulthood and aging.

Brain responses to facial attractiveness induced by facial proportions: evidence from an fMRI study

PubMed Central

Shen, Hui; Chau, Desmond K. P.; Su, Jianpo; Zeng, Ling-Li; Jiang, Weixiong; He, Jufang; Fan, Jintu; Hu, Dewen

2016-01-01

Brain responses to facial attractiveness induced by facial proportions are investigated by using functional magnetic resonance imaging (fMRI), in 41 young adults (22 males and 19 females). The subjects underwent fMRI while they were presented with computer-generated, yet realistic face images, which had varying facial proportions, but the same neutral facial expression, baldhead and skin tone, as stimuli. Statistical parametric mapping with parametric modulation was used to explore the brain regions with the response modulated by facial attractiveness ratings (ARs). The results showed significant linear effects of the ARs in the caudate nucleus and the orbitofrontal cortex for all of the subjects, and a non-linear response profile in the right amygdala for only the male subjects. Furthermore, canonical correlation analysis was used to learn the most relevant facial ratios that were best correlated with facial attractiveness. A regression model on the fMRI-derived facial ratio components demonstrated a strong linear relationship between the visually assessed mean ARs and the predictive ARs. Overall, this study provided, for the first time, direct neurophysiologic evidence of the effects of facial ratios on facial attractiveness and suggested that there are notable gender differences in perceiving facial attractiveness as induced by facial proportions. PMID:27779211

Brain responses to facial attractiveness induced by facial proportions: evidence from an fMRI study.

PubMed

Shen, Hui; Chau, Desmond K P; Su, Jianpo; Zeng, Ling-Li; Jiang, Weixiong; He, Jufang; Fan, Jintu; Hu, Dewen

2016-10-25

Brain responses to facial attractiveness induced by facial proportions are investigated by using functional magnetic resonance imaging (fMRI), in 41 young adults (22 males and 19 females). The subjects underwent fMRI while they were presented with computer-generated, yet realistic face images, which had varying facial proportions, but the same neutral facial expression, baldhead and skin tone, as stimuli. Statistical parametric mapping with parametric modulation was used to explore the brain regions with the response modulated by facial attractiveness ratings (ARs). The results showed significant linear effects of the ARs in the caudate nucleus and the orbitofrontal cortex for all of the subjects, and a non-linear response profile in the right amygdala for only the male subjects. Furthermore, canonical correlation analysis was used to learn the most relevant facial ratios that were best correlated with facial attractiveness. A regression model on the fMRI-derived facial ratio components demonstrated a strong linear relationship between the visually assessed mean ARs and the predictive ARs. Overall, this study provided, for the first time, direct neurophysiologic evidence of the effects of facial ratios on facial attractiveness and suggested that there are notable gender differences in perceiving facial attractiveness as induced by facial proportions.

Vagus-brain communication in atherosclerosis-related inflammation: a neuroimmunomodulation perspective of CAD.

PubMed

Gidron, Yori; Kupper, Nina; Kwaijtaal, Martijn; Winter, Jobst; Denollet, Johan

2007-12-01

The current understanding of the pathophysiology of atherosclerosis leading to coronary artery disease (CAD) emphasizes the role of inflammatory mediators. Given the bidirectional communication between the immune and central nervous systems, an important question is whether the brain can be "informed" about and modulate CAD-related inflammation. A candidate communicator and modulator is the vagus nerve. Until now, the vagus nerve has received attention in cardiology mainly due to its role in the parasympathetic cardiovascular response. However, the vagus nerve can also "inform" the brain about peripheral inflammation since its paraganglia have receptors for interleukin-1. Furthermore, its efferent branch has a local anti-inflammatory effect. These effects have not been considered in research on the vagus nerve in CAD or in vagus nerve stimulation trials in CAD. In addition, various behavioural interventions, including relaxation, may influence CAD prognosis by affecting vagal activity. Based on this converging evidence, we propose a neuroimmunomodulation approach to atherogenesis. In this model, the vagus nerve "informs" the brain about CAD-related cytokines; in turn, activation of the vagus (via vagus nerve stimulation, vagomimetic drugs or relaxation) induces an anti-inflammatory response that can slow down the chronic process of atherogenesis.

Neural responses of rat cortical layers due to infrared neural modulation and photoablation of thalamocortical brain slices

NASA Astrophysics Data System (ADS)

Jenkins, J. Logan; Kao, Chris C.; Cayce, Jonathan M.; Mahadevan-Jansen, Anita; Jansen, E. Duco

2017-02-01

Infrared neural modulation (INM) is a label-free method for eliciting neural activity with high spatial selectivity in mammalian models. While there has been an emphasis on INM research towards applications in the peripheral nervous system and the central nervous system (CNS), the biophysical mechanisms by which INM occurs remains largely unresolved. In the rat CNS, INM has been shown to elicit and inhibit neural activity, evoke calcium signals that are dependent on glutamate transients and astrocytes, and modulate inhibitory GABA currents. So far, in vivo experiments have been restricted to layers I and II of the rat cortex which consists mainly of astrocytes, inhibitory neurons, and dendrites from deeper excitatory neurons owing to strong absorption of light in these layers. Deeper cortical layers (III-VI) have vastly different cell type composition, consisting predominantly of excitatory neurons which can be targeted for therapies such as deep brain stimulation. The neural responses to infrared light of deeper cortical cells have not been well defined. Acute thalamocortical brain slices will allow us to analyze the effects of INS on various components of the cortex, including different cortical layers and cell populations. In this study, we present the use of photoablation with an erbium:YAG laser to reduce the thickness of the dead cell zone near the cutting surface of brain slices. This technique will allow for more optical energy to reach living cells, which should contribute the successful transduction of pulsed infrared light to neural activity. In the future, INM-induced neural responses will lead to a finer characterization of the parameter space for the neuromodulation of different cortical cell types and may contribute to understanding the cell populations that are important for allowing optical stimulation of neurons in the CNS.

Mental fatigue and impaired response processes: event-related brain potentials in a Go/NoGo task.

PubMed

Kato, Yuichiro; Endo, Hiroshi; Kizuka, Tomohiro

2009-05-01

The effects of mental fatigue on the availability of cognitive resources and associated response-related processes were examined using event-related brain potentials. Subjects performed a Go/NoGo task for 60 min. Reaction time, number of errors, and mental fatigue scores all significantly increased with time spent on the task. The NoGo-P3 amplitude significantly decreased with time on task, but the Go-P3 amplitude was not modulated. The amplitude of error-related negativity (Ne/ERN) also decreased with time on task. These results indicate that mental fatigue attenuates resource allocation and error monitoring for NoGo stimuli. The Go- and NoGo-P3 latencies both increased with time on task, indicative of a delay in stimulus evaluation time due to mental fatigue. NoGo-N2 latency increased with time on task, but NoGo-N2 amplitude was not modulated. The amplitude of response-locked lateralized readiness potential (LRP) significantly decreased with time on task. Mental fatigue appears to slows down the time course of response inhibition, and impairs the intensity of response execution.

Neurophysiology of hypnosis.

PubMed

Vanhaudenhuyse, A; Laureys, S; Faymonville, M-E

2014-10-01

We here review behavioral, neuroimaging and electrophysiological studies of hypnosis as a state, as well as hypnosis as a tool to modulate brain responses to painful stimulations. Studies have shown that hypnotic processes modify internal (self awareness) as well as external (environmental awareness) brain networks. Brain mechanisms underlying the modulation of pain perception under hypnotic conditions involve cortical as well as subcortical areas including anterior cingulate and prefrontal cortices, basal ganglia and thalami. Combined with local anesthesia and conscious sedation in patients undergoing surgery, hypnosis is associated with improved peri- and postoperative comfort of patients and surgeons. Finally, hypnosis can be considered as a useful analogue for simulating conversion and dissociation symptoms in healthy subjects, permitting better characterization of these challenging disorders by producing clinically similar experiences. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Biological sources of inflexibility in brain and behavior with aging and neurodegenerative diseases

PubMed Central

Hong, S. Lee; Rebec, George V.

2012-01-01

Almost unequivocally, aging and neurodegeneration lead to deficits in neural information processing. These declines are marked by increased neural noise that is associated with increased variability or inconsistency in behavioral patterns. While it is often viewed that these problems arise from dysregulation of dopamine (DA), a monoamine modulator, glutamate (GLU), an excitatory amino acid that interacts with DA, also plays a role in determining the level of neural noise. We review literature demonstrating that neural noise is highest at both high and low levels of DA and GLU, allowing their interaction to form a many-to-one solution map for neural noise modulation. With aging and neurodegeneration, the range over which DA and GLU can be modulated is decreased leading to inflexibility in brain activity and behavior. As the capacity to modulate neural noise is restricted, the ability to shift noise from one brain region to another is reduced, leading to greater uniformity in signal-to-noise ratios across the entire brain. A negative consequence at the level of behavior is inflexibility that reduces the ability to: (1) switch from one behavior to another; and (2) stabilize a behavioral pattern against external perturbations. In this paper, we develop a theoretical framework where inflexibility across brain and behavior, rather than inconsistency and variability is the more important problem in aging and neurodegeneration. This theoretical framework of inflexibility in aging and neurodegeneration leads to the hypotheses that: (1) dysfunction in either or both of the DA and GLU systems restricts the ability to modulate neural noise; and (2) levels of neural noise and variability in brain activation will be dedifferentiated and more evenly distributed across the brain; and (3) changes in neural noise and behavioral variability in response to different task demands and changes in the environment will be reduced. PMID:23226117

Task modulations of racial bias in neural responses to others' suffering.

PubMed

Sheng, Feng; Liu, Qiang; Li, Hong; Fang, Fang; Han, Shihui

2014-03-01

Recent event related brain potential research observed a greater frontal activity to pain expressions of racial in-group than out-group members and such racial bias in neural responses to others' suffering was modulated by task demands that emphasize race identity or painful feeling. However, as pain expressions activate multiple brain regions in the pain matrix, it remains unclear which part of the neural circuit in response to others' suffering undergoes modulations by task demands. We scanned Chinese adults, using functional MRI, while they categorized Asian and Caucasian faces with pain or neutral expressions in terms of race or identified painful feelings of each individual face. We found that pain vs. neutral expressions of Asian but not Caucasian faces activated the anterior cingulate (ACC) and anterior insular (AI) activity during race judgments. However, pain compared to race judgments increased ACC and AI activity to pain expressions of Caucasian but not Asian faces. Moreover, race judgments induced increased activity in the dorsal medial prefrontal cortex whereas pain judgments increased activity in the bilateral temporoparietal junction. The results suggest that task demands emphasizing an individual's painful feeling increase ACC/AI activities to pain expressions of racial out-group members and reduce the racial bias in empathic neural responses. © 2013.

Spatio-temporal brain dynamics in a combined stimulus-stimulus and stimulus-response conflict task.

PubMed

Frühholz, Sascha; Godde, Ben; Finke, Mareike; Herrmann, Manfred

2011-01-01

It is yet not well known whether different types of conflicts share common or rely on distinct brain mechanisms of conflict processing. We used a combined Flanker (stimulus-stimulus; S-S) and Simon (stimulus-response; S-R) conflict paradigm both in an fMRI and an EEG study. S-S conflicts induced stronger behavioral interference effects compared to S-R conflicts and the latter decayed with increasing response latencies. Besides some similar medial frontal activity across all conflict trials, which was, however, not statically consistent across trials, we especially found distinct activations depending on the type of conflict. S-S conflicts activated the anterior cingulate cortex and modulated the N2 and early P3 component with underlying source activity in inferior frontal cortex. S-R conflicts produced distinct activations in the posterior cingulate cortex and modulated the late P3b component with underlying source activity in superior parietal cortex. Double conflict trials containing both S-S and S-R conflicts revealed, first, distinct anterior frontal activity representing a meta-processing unit and, second, a sequential modulation of the N2 and the P3b component. The N2 modulation during double conflict trials was accompanied by increased source activity in the medial frontal gyrus (MeFG). In summary, S-S and S-R conflict processing mostly rely on distinct mechanisms of conflict processing and these conflicts differentially modulate the temporal stages of stimulus processing. Copyright © 2010 Elsevier Inc. All rights reserved.

Pharmacological modulation of the voltage-gated neuronal Kv7/KCNQ/M-channel alters the intrinsic excitability and synaptic responses of pyramidal neurons in rat prefrontal cortex slices.

PubMed

Peng, Hui; Bian, Xi-Ling; Ma, Fu-Cui; Wang, Ke-Wei

2017-09-01

The prefrontal cortex (PFC) critical for higher cognition is implicated in neuropsychiatric diseases, such as Alzheimer's disease, depression and schizophrenia. The voltage-activated Kv7/KCNQ/M-channel or M-current modulates the neuronal excitability that defines the fundamental mechanism of brain function. However, whether M-current functions to regulate the excitability of PFC neurons remains elusive. In this study, we recorded the native M-current from PFC layer V pyramidal neurons in rat brain slices and showed that it modulated the intrinsic excitability and synaptic responses of PFC pyramidal neurons. Application of a specific M-channel blocker XE991 (40 μmol/L) or opener retigabine (10 μmol/L) resulted in inhibition or activation of M-current, respectively. In the current-clamp recordings, inhibition of M-current was evidenced by the increased average spike frequency and the reduced first inter-spike interval (ISI), spike onset latency and fast afterhyperpolarization (fAHP), whereas activation of M-current caused opposite responses. Furthermore, inhibition of M-current significantly increased the amplitude of excitatory postsynaptic potentials (EPSPs) and depolarized the resting membrane potential (RMP) without affecting the miniature EPSC (mEPSC) frequency. These data demonstrate that voltage-gated neuronal Kv7/KCNQ/M-current modulates the excitability and synaptic transmission of PFC neurons, suggesting that pharmacological modulation of M-current in the PFC may exert beneficial effects on cognitive deficits implicated in the pathophysiology of neuropsychiatric disorders.

Functional Imaging of Audio-Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

PubMed

Rinne, Teemu; Muers, Ross S; Salo, Emma; Slater, Heather; Petkov, Christopher I

2017-06-01

The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio-visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio-visual selective attention modulates the primate brain, identify sources for "lost" attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. © The Author 2017. Published by Oxford University Press.

Functional Imaging of Audio–Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

PubMed Central

Muers, Ross S.; Salo, Emma; Slater, Heather; Petkov, Christopher I.

2017-01-01

Abstract The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio–visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio–visual selective attention modulates the primate brain, identify sources for “lost” attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. PMID:28419201

Serotonin and the neural processing of facial emotions in adults with autism: an fMRI study using acute tryptophan depletion.

PubMed

Daly, Eileen M; Deeley, Quinton; Ecker, Christine; Craig, Michael; Hallahan, Brian; Murphy, Clodagh; Johnston, Patrick; Spain, Debbie; Gillan, Nicola; Brammer, Michael; Giampietro, Vincent; Lamar, Melissa; Page, Lisa; Toal, Fiona; Cleare, Anthony; Surguladze, Simon; Murphy, Declan G M

2012-10-01

People with autism spectrum disorders (ASDs) have lifelong deficits in social behavior and differences in behavioral as well as neural responses to facial expressions of emotion. The biological basis to this is incompletely understood, but it may include differences in the role of neurotransmitters such as serotonin, which modulate facial emotion processing in health. While some individuals with ASD have significant differences in the serotonin system, to our knowledge, no one has investigated its role during facial emotion processing in adults with ASD and control subjects using acute tryptophan depletion (ATD) and functional magnetic resonance imaging. To compare the effects of ATD on brain responses to primary facial expressions of emotion in men with ASD and healthy control subjects. Double-blind, placebo-controlled, crossover trial of ATD and functional magnetic resonance imaging to measure brain activity during incidental processing of disgust, fearful, happy, and sad facial expressions. Institute of Psychiatry, King's College London, and South London and Maudsley National Health Service Foundation Trust, England. Fourteen men of normal intelligence with autism and 14 control subjects who did not significantly differ in sex, age, or overall intelligence. Blood oxygenation level-dependent response to facial expressions of emotion. Brain activation was differentially modulated by ATD depending on diagnostic group and emotion type within regions of the social brain network. For example, processing of disgust faces was associated with interactions in medial frontal and lingual gyri, whereas processing of happy faces was associated with interactions in middle frontal gyrus and putamen. Modulation of the processing of facial expressions of emotion by serotonin significantly differs in people with ASD compared with control subjects. The differences vary with emotion type and occur in social brain regions that have been shown to be associated with group differences in serotonin synthesis/receptor or transporter density.

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

PubMed

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

2018-05-01

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

The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors.

PubMed

Paul, Steven M; Doherty, James J; Robichaud, Albert J; Belfort, Gabriel M; Chow, Brian Y; Hammond, Rebecca S; Crawford, Devon C; Linsenbardt, Andrew J; Shu, Hong-Jin; Izumi, Yukitoshi; Mennerick, Steven J; Zorumski, Charles F

2013-10-30

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are critical to the regulation of excitatory synaptic function in the CNS. NMDARs govern experience-dependent synaptic plasticity and have been implicated in the pathophysiology of various neuropsychiatric disorders including the cognitive deficits of schizophrenia and certain forms of autism. Certain neurosteroids modulate NMDARs experimentally but their low potency, poor selectivity, and very low brain concentrations make them poor candidates as endogenous ligands or therapeutic agents. Here we show that the major brain-derived cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-HC) is a very potent, direct, and selective positive allosteric modulator of NMDARs with a mechanism that does not overlap that of other allosteric modulators. At submicromolar concentrations 24(S)-HC potentiates NMDAR-mediated EPSCs in rat hippocampal neurons but fails to affect AMPAR or GABAA receptors (GABA(A)Rs)-mediated responses. Cholesterol itself and other naturally occurring oxysterols present in brain do not modulate NMDARs at concentrations ≤10 μM. In hippocampal slices, 24(S)-HC enhances the ability of subthreshold stimuli to induce long-term potentiation (LTP). 24(S)-HC also reverses hippocampal LTP deficits induced by the NMDAR channel blocker ketamine. Finally, we show that synthetic drug-like derivatives of 24(S)-HC, which potently enhance NMDAR-mediated EPSCs and LTP, restore behavioral and cognitive deficits in rodents treated with NMDAR channel blockers. Thus, 24(S)-HC may function as an endogenous modulator of NMDARs acting at a novel oxysterol modulatory site that also represents a target for therapeutic drug development.

Brain Circuitry Supporting Multi-Organ Autonomic Outflow in Response to Nausea.

PubMed

Sclocco, Roberta; Kim, Jieun; Garcia, Ronald G; Sheehan, James D; Beissner, Florian; Bianchi, Anna M; Cerutti, Sergio; Kuo, Braden; Barbieri, Riccardo; Napadow, Vitaly

2016-02-01

While autonomic outflow is an important co-factor of nausea physiology, central control of this outflow is poorly understood. We evaluated sympathetic (skin conductance level) and cardiovagal (high-frequency heart rate variability) modulation, collected synchronously with functional MRI (fMRI) data during nauseogenic visual stimulation aimed to induce vection in susceptible individuals. Autonomic data guided analysis of neuroimaging data, using a stimulus-based (analysis windows set by visual stimulation protocol) and percept-based (windows set by subjects' ratings) approach. Increased sympathetic and decreased parasympathetic modulation was associated with robust and anti-correlated brain activity in response to nausea. Specifically, greater autonomic response was associated with reduced fMRI signal in brain regions such as the insula, suggesting an inhibitory relationship with premotor brainstem nuclei. Interestingly, some sympathetic/parasympathetic specificity was noted. Activity in default mode network and visual motion areas was anti-correlated with parasympathetic outflow at peak nausea. In contrast, lateral prefrontal cortical activity was anti-correlated with sympathetic outflow during recovery, soon after cessation of nauseogenic stimulation. These results suggest divergent central autonomic control for sympathetic and parasympathetic response to nausea. Autonomic outflow and the central autonomic network underlying ANS response to nausea may be an important determinant of overall nausea intensity and, ultimately, a potential therapeutic target. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Color of scents: chromatic stimuli modulate odor responses in the human brain.

PubMed

Osterbauer, Robert A; Matthews, Paul M; Jenkinson, Mark; Beckmann, Christian F; Hansen, Peter C; Calvert, Gemma A

2005-06-01

Color has a profound effect on the perception of odors. For example, strawberry-flavored drinks smell more pleasant when colored red than green and descriptions of the "nose" of a wine are dramatically influenced by its color. Using functional magnetic resonance imaging, we demonstrate a neurophysiological correlate of these cross-modal visual influences on olfactory perception. Subjects were scanned while exposed either to odors or colors in isolation or to color-odor combinations that were rated on the basis of how well they were perceived to match. Activity in caudal regions of the orbitofrontal cortex and in the insular cortex increased progressively with the perceived congruency of the odor-color pairs. These findings demonstrate the neuronal correlates of olfactory response modulation by color cues in brain areas previously identified as encoding the hedonic value of smells.

Brain systems underlying encounter expectancy bias in spider phobia.

PubMed

Aue, Tatjana; Hoeppli, Marie-Eve; Piguet, Camille; Hofstetter, Christoph; Rieger, Sebastian W; Vuilleumier, Patrik

2015-06-01

Spider-phobic individuals are characterized by exaggerated expectancies to be faced with spiders (so-called encounter expectancy bias). Whereas phobic responses have been linked to brain systems mediating fear, little is known about how the recruitment of these systems relates to exaggerated expectancies of threat. We used fMRI to examine spider-phobic and control participants while they imagined visiting different locations in a forest after having received background information about the likelihood of encountering different animals (spiders, snakes, and birds) at these locations. Critically, imagined encounter expectancies modulated brain responses differently in phobics as compared with controls. Phobics displayed stronger negative modulation of activity in the lateral prefrontal cortex, precuneus, and visual cortex by encounter expectancies for spiders, relative to snakes or birds (within-participants analysis); these effects were not seen in controls. Between-participants correlation analyses within the phobic group further corroborated the hypothesis that these phobia-specific modulations may underlie irrationality in encounter expectancies (deviations of encounter expectancies from objective background information) in spider phobia; the greater the negative modulation a phobic participant displayed in the lateral prefrontal cortex, precuneus, and visual cortex, the stronger was her bias in encounter expectancies for spiders. Interestingly, irrationality in expectancies reflected in frontal areas relied on right rather than left hemispheric deactivations. Our data accord with the idea that expectancy biases in spider phobia may reflect deficiencies in cognitive control and contextual integration that are mediated by right frontal and parietal areas.

Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost in Patients With Brain Oligometastases: A Phase 1 Study (ISIDE-BM-1)

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

Ferro, Marica; Chiesa, Silvia; Macchia, Gabriella, E-mail: gmacchia@rm.unicatt.it

Purpose: To investigate the maximum tolerated dose of intensity modulated radiation therapy simultaneous integrated boost whole-brain radiation therapy for palliative treatment of patients with <5 brain metastases using a standard linear accelerator. Materials and Methods: The whole brain plus 3-mm margin was defined as the planning target volume (PTV{sub wb}), whereas each brain metastasis, defined as the contrast-enhancing tumor on MRI T1 scans, plus a 3-mm isotropic margin, was defined as metastases PTV (PTV{sub m}). Radiation therapy was delivered in 10 daily fractions (2 weeks). Only the dose to PTV{sub m} was progressively increased in the patient cohorts (35 Gy, 40 Gy, 45 Gy, 50 Gy),more » whereas the PTV{sub wb} was always treated with 30 Gy (3 Gy per fraction) in all patients. The dose-limiting toxicity was evaluated providing that 3 months of follow-up had occurred after the treatment of a 6-patient cohort. Results: Thirty patients were enrolled in the study (dose PTV{sub m}: 35 Gy, 8 patients; 40 Gy, 6 patients; 45 Gy, 6 patients; 50 Gy, 10 patients). The number of treated brain metastases was 1 in 18 patients, 2 in 5 patients, 3 in 6 patients, and 4 in 1 patient. Three patients experienced dose-limiting toxicity: 1 patient at dose level 2 presented grade 3 (G3) skin toxicity; 1 patient at dose level 4 presented G3 neurologic toxicity; and 1 patient at the same level showed brain hemorrhage. Most patients showed G1 to 2 acute toxicity, in most cases skin (n=19) or neurologic (n=10). Twenty-seven were evaluable for response: 6 (22%) stable disease, 18 (67%) partial response, and 3 (11%) complete response. Median survival and 1-year overall survival were 12 months and 53%, respectively. No patient showed late toxicity. Conclusions: In this first prospective trial on the use of intensity modulated radiation therapy simultaneous integrated boost delivered with a standard linear accelerator in patients with brain oligometastases, a boost dose up to 50 Gy in 10 fractions was tolerable according to the study design.« less

The Fate of Incoming Stimuli during NREM Sleep is Determined by Spindles and the Phase of the Slow Oscillation.

PubMed

Schabus, Manuel; Dang-Vu, Thien Thanh; Heib, Dominik Philip Johannes; Boly, Mélanie; Desseilles, Martin; Vandewalle, Gilles; Schmidt, Christina; Albouy, Geneviève; Darsaud, Annabelle; Gais, Steffen; Degueldre, Christian; Balteau, Evelyne; Phillips, Christophe; Luxen, André; Maquet, Pierre

2012-01-01

The present study aimed at identifying the neurophysiological responses associated with auditory stimulation during non-rapid eye movement (NREM) sleep using simultaneous electroencephalography (EEG)/functional magnetic resonance imaging (fMRI) recordings. It was reported earlier that auditory stimuli produce bilateral activation in auditory cortex, thalamus, and caudate during both wakefulness and NREM sleep. However, due to the spontaneous membrane potential fluctuations cortical responses may be highly variable during NREM. Here we now examine the modulation of cerebral responses to tones depending on the presence or absence of sleep spindles and the phase of the slow oscillation. Thirteen healthy young subjects were scanned successfully during stage 2-4 NREM sleep in the first half of the night in a 3 T scanner. Subjects were not sleep-deprived and sounds were post hoc classified according to (i) the presence of sleep spindles or (ii) the phase of the slow oscillation during (±300 ms) tone delivery. These detected sounds were then entered as regressors of interest in fMRI analyses. Interestingly wake-like responses - although somewhat altered in size and location - persisted during NREM sleep, except during present spindles (as previously published in Dang-Vu et al., 2011) and the negative going phase of the slow oscillation during which responses became less consistent or even absent. While the phase of the slow oscillation did not alter brain responses in primary sensory cortex, it did modulate responses at higher cortical levels. In addition EEG analyses show a distinct N550 response to tones during the presence of light sleep spindles and suggest that in deep NREM sleep the brain is more responsive during the positive going slope of the slow oscillation. The presence of short temporal windows during which the brain is open to external stimuli is consistent with the fact that even during deep sleep meaningful events can be detected. Altogether, our results emphasize the notion that spontaneous fluctuations of brain activity profoundly modify brain responses to external information across all behavioral states, including deep NREM sleep.

Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays.

PubMed

Panuccio, Gabriella; Colombi, Ilaria; Chiappalone, Michela

2018-05-15

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) is a promising approach when pharmacological treatment fails or neurosurgery is not recommended. Acute brain slices coupled to microelectrode arrays (MEAs) represent a valuable tool to study neuronal network interactions and their modulation by electrical stimulation. As compared to conventional extracellular recording techniques, they provide the added advantages of a greater number of observation points and a known inter-electrode distance, which allow studying the propagation path and speed of electrophysiological signals. However, tissue oxygenation may be greatly impaired during MEA recording, requiring a high perfusion rate, which comes at the cost of decreased signal-to-noise ratio and higher oscillations in the experimental temperature. Electrical stimulation further stresses the brain tissue, making it difficult to pursue prolonged recording/stimulation epochs. Moreover, electrical modulation of brain slice activity needs to target specific structures/pathways within the brain slice, requiring that electrode mapping be easily and quickly performed live during the experiment. Here, we illustrate how to perform the recording and electrical modulation of 4-aminopyridine (4AP)-induced epileptiform activity in rodent brain slices using planar MEAs. We show that the brain tissue obtained from mice outperforms rat brain tissue and is thus better suited for MEA experiments. This protocol guarantees the generation and maintenance of a stable epileptiform pattern that faithfully reproduces the electrophysiological features observed with conventional field potential recording, persists for several hours, and outlasts sustained electrical stimulation for prolonged epochs. Tissue viability throughout the experiment is achieved thanks to the use of a small-volume custom recording chamber allowing for laminar flow and quick solution exchange even at low (1 mL/min) perfusion rates. Quick MEA mapping for real-time monitoring and selection of stimulating electrodes is performed by a custom graphic user interface (GUI).

Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation.

PubMed

Neuling, Toralf; Ruhnau, Philipp; Fuscà, Marco; Demarchi, Gianpaolo; Herrmann, Christoph S; Weisz, Nathan

2015-09-01

Brain oscillations are supposedly crucial for normal cognitive functioning and alterations are associated with cognitive dysfunctions. To demonstrate their causal role on behavior, entrainment approaches in particular aim at driving endogenous oscillations via rhythmic stimulation. Within this context, transcranial electrical stimulation, especially transcranial alternating current stimulation (tACS), has received renewed attention. This is likely due to the possibility of defining oscillatory stimulation properties precisely. Also, measurements comparing pre-tACS with post-tACS electroencephalography (EEG) have shown impressive modulations. However, the period during tACS has remained a blackbox until now, due to the enormous stimulation artifact. By means of application of beamforming to magnetoencephalography (MEG) data, we successfully recovered modulations of the amplitude of brain oscillations during weak and strong tACS. Additionally, we demonstrate that also evoked responses to visual and auditory stimuli can be recovered during tACS. The main contribution of the present study is to provide critical evidence that during ongoing tACS, subtle modulations of oscillatory brain activity can be reconstructed even at the stimulation frequency. Future tACS experiments will be able to deliver direct physiological insights in order to further the understanding of the contribution of brain oscillations to cognition and behavior. Copyright © 2015. Published by Elsevier Inc.

Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation

PubMed Central

Neuling, Toralf; Ruhnau, Philipp; Fuscà, Marco; Demarchi, Gianpaolo; Herrmann, Christoph S.; Weisz, Nathan

2015-01-01

Brain oscillations are supposedly crucial for normal cognitive functioning and alterations are associated with cognitive dysfunctions. To demonstrate their causal role on behavior, entrainment approaches in particular aim at driving endogenous oscillations via rhythmic stimulation. Within this context, transcranial electrical stimulation, especially transcranial alternating current stimulation (tACS), has received renewed attention. This is likely due to the possibility of defining oscillatory stimulation properties precisely. Also, measurements comparing pre-tACS with post-tACS electroencephalography (EEG) have shown impressive modulations. However, the period during tACS has remained a blackbox until now, due to the enormous stimulation artifact. By means of application of beamforming to magnetoencephalography (MEG) data, we successfully recovered modulations of the amplitude of brain oscillations during weak and strong tACS. Additionally, we demonstrate that also evoked responses to visual and auditory stimuli can be recovered during tACS. The main contribution of the present study is to provide critical evidence that during ongoing tACS, subtle modulations of oscillatory brain activity can be reconstructed even at the stimulation frequency. Future tACS experiments will be able to deliver direct physiological insights in order to further the understanding of the contribution of brain oscillations to cognition and behavior. PMID:26080310

Memory modulation across neural systems: intra-amygdala glucose reverses deficits caused by intraseptal morphine on a spatial task but not on an aversive task.

PubMed

McNay, E C; Gold, P E

1998-05-15

Based largely on dissociations of the effects of different lesions on learning and memory, memories for different attributes appear to be organized in independent neural systems. Results obtained with direct injections of drugs into one brain region at a time support a similar conclusion. The present experiments investigated the effects of simultaneous pharmacological manipulation of two neural systems, the amygdala and the septohippocampal system, to examine possible interactions of memory modulation across systems. Morphine injected into the medial septum impaired memory both for avoidance training and during spontaneous alternation. When glucose was concomitantly administered to the amygdala, glucose reversed the morphine-induced deficits in memory during alternation but not for avoidance training. These results suggest that the amygdala is involved in modulation of spatial memory processes and that direct injections of memory-modulating drugs into the amygdala do not always modulate memory for aversive events. These findings are contrary to predictions from the findings of lesion studies and of studies using direct injections of drugs into single brain areas. Thus, the independence of neural systems responsible for processing different classes of memory is less clear than implied by studies using lesions or injections of drugs into single brain areas.

Increased Anatomical Specificity of Neuromodulation via Modulated Focused Ultrasound

PubMed Central

Mehić, Edin; Xu, Julia M.; Caler, Connor J.; Coulson, Nathaniel K.; Moritz, Chet T.; Mourad, Pierre D.

2014-01-01

Transcranial ultrasound can alter brain function transiently and nondestructively, offering a new tool to study brain function now and inform future therapies. Previous research on neuromodulation implemented pulsed low-frequency (250–700 kHz) ultrasound with spatial peak temporal average intensities (ISPTA) of 0.1–10 W/cm2. That work used transducers that either insonified relatively large volumes of mouse brain (several mL) with relatively low-frequency ultrasound and produced bilateral motor responses, or relatively small volumes of brain (on the order of 0.06 mL) with relatively high-frequency ultrasound that produced unilateral motor responses. This study seeks to increase anatomical specificity to neuromodulation with modulated focused ultrasound (mFU). Here, ‘modulated’ means modifying a focused 2-MHz carrier signal dynamically with a 500-kHz signal as in vibro-acoustography, thereby creating a low-frequency but small volume (approximately 0.015 mL) source of neuromodulation. Application of transcranial mFU to lightly anesthetized mice produced various motor movements with high spatial selectivity (on the order of 1 mm) that scaled with the temporal average ultrasound intensity. Alone, mFU and focused ultrasound (FUS) each induced motor activity, including unilateral motions, though anatomical location and type of motion varied. Future work should include larger animal models to determine the relative efficacy of mFU versus FUS. Other studies should determine the biophysical processes through which they act. Also of interest is exploration of the potential research and clinical applications for targeted, transcranial neuromodulation created by modulated focused ultrasound, especially mFU’s ability to produce compact sources of ultrasound at the very low frequencies (10–100s of Hertz) that are commensurate with the natural frequencies of the brain. PMID:24504255

The nicotinic receptor blocker hexamethonium alters neuronal responses to glutamate in the medial septal area of the brain of the ground squirrel in vitro.

PubMed

Karavaev, E N; Popova, I Yu; Kichigina, V F

2008-03-01

Despite extensive interest in studies of the medial septal area, the nature of the interactions of its various neurochemical systems remains largely unclear. The aim of the present work was to clarify the role of nicotinic receptors in mediating the interaction of the glutamatergic and cholinergic systems in this structure. Extracellular recording of neuron activity in living slices of ground squirrel brain was used to study the influences of L-glutamate (1 microM) during application of the nicotinic receptor blocker hexamethonium (1 mM). The responses of septal neurons to glutamate depended on the type of their initial activity and the presence of pacemaker properties. This study is the first to show that glutamate increases the frequency of volleys in rhythmic neurons in the septum. Hexamethonium induced changes in neuron activity similar to the influences of glutamate. After prior application of hexamethonium, the responses of neurons to glutamate changed: activatory responses were masked and inhibitory responses were enhanced. Cholinergic modulation of the responses of septal neurons to glutamate were shown to occur, as did modulation of the strength of the oscillatory properties of the septal network by nicotinic receptors.

EEG neural oscillatory dynamics reveal semantic and response conflict at difference levels of conflict awareness

PubMed Central

Jiang, Jun; Zhang, Qinglin; Van Gaal, Simon

2015-01-01

Although previous work has shown that conflict can be detected in the absence of awareness, it is unknown how different sources of conflict (i.e., semantic, response) are processed in the human brain and whether these processes are differently modulated by conflict awareness. To explore this issue, we extracted oscillatory power dynamics from electroencephalographic (EEG) data recorded while human participants performed a modified version of the Stroop task. Crucially, in this task conflict awareness was manipulated by masking a conflict-inducing color word preceding a color patch target. We isolated semantic from response conflict by introducing four color words/patches, of which two were matched to the same response. We observed that both semantic as well as response conflict were associated with mid-frontal theta-band and parietal alpha-band power modulations, irrespective of the level of conflict awareness (high vs. low), although awareness of conflict increased these conflict-related power dynamics. These results show that both semantic and response conflict can be processed in the human brain and suggest that the neural oscillatory mechanisms in EEG reflect mainly “domain general” conflict processing mechanisms, instead of conflict source specific effects. PMID:26169473

EEG neural oscillatory dynamics reveal semantic and response conflict at difference levels of conflict awareness.

PubMed

Jiang, Jun; Zhang, Qinglin; Van Gaal, Simon

2015-07-14

Although previous work has shown that conflict can be detected in the absence of awareness, it is unknown how different sources of conflict (i.e., semantic, response) are processed in the human brain and whether these processes are differently modulated by conflict awareness. To explore this issue, we extracted oscillatory power dynamics from electroencephalographic (EEG) data recorded while human participants performed a modified version of the Stroop task. Crucially, in this task conflict awareness was manipulated by masking a conflict-inducing color word preceding a color patch target. We isolated semantic from response conflict by introducing four color words/patches, of which two were matched to the same response. We observed that both semantic as well as response conflict were associated with mid-frontal theta-band and parietal alpha-band power modulations, irrespective of the level of conflict awareness (high vs. low), although awareness of conflict increased these conflict-related power dynamics. These results show that both semantic and response conflict can be processed in the human brain and suggest that the neural oscillatory mechanisms in EEG reflect mainly "domain general" conflict processing mechanisms, instead of conflict source specific effects.

Effective connectivity of ascending and descending frontalthalamic pathways during sustained attention: Complex brain network interactions in adolescence.

PubMed

Jagtap, Pranav; Diwadkar, Vaibhav A

2016-07-01

Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals [dynamic causal modeling (DCM)] to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectures were employed in DCM to evaluate hypotheses on bilateral frontal-thalamic connections and their modulation by attention demand, selected at a second level using Bayesian model selection. The model architecture evinced significant contextual modulation by attention of ascending (thalamus → dPFC) and descending (dPFC → thalamus) pathways. However, modulation of these pathways was asymmetric: while positive modulation of the ascending pathway was comparable across attention demand, modulation of the descending pathway was significantly greater when attention demands were increased. Increased modulation of the (dPFC → thalamus) pathway in response to increased attention demand constitutes novel evidence of attention-related gain in the connectivity of the descending attention pathway. By comparison demand-independent modulation of the ascending (thalamus → dPFC) pathway suggests unbiased thalamic inputs to the cortex in the context of the paradigm. Hum Brain Mapp 37:2557-2570, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The neuropeptide tachykinin is essential for pheromone detection in a gustatory neural circuit

PubMed Central

Shankar, Shruti; Chua, Jia Yi; Tan, Kah Junn; Calvert, Meredith EK; Weng, Ruifen; Ng, Wan Chin; Mori, Kenji; Yew, Joanne Y

2015-01-01

Gustatory pheromones play an essential role in shaping the behavior of many organisms. However, little is known about the processing of taste pheromones in higher order brain centers. Here, we describe a male-specific gustatory circuit in Drosophila that underlies the detection of the anti-aphrodisiac pheromone (3R,11Z,19Z)-3-acetoxy-11,19-octacosadien-1-ol (CH503). Using behavioral analysis, genetic manipulation, and live calcium imaging, we show that Gr68a-expressing neurons on the forelegs of male flies exhibit a sexually dimorphic physiological response to the pheromone and relay information to the central brain via peptidergic neurons. The release of tachykinin from 8 to 10 cells within the subesophageal zone is required for the pheromone-triggered courtship suppression. Taken together, this work describes a neuropeptide-modulated central brain circuit that underlies the programmed behavioral response to a gustatory sex pheromone. These results will allow further examination of the molecular basis by which innate behaviors are modulated by gustatory cues and physiological state. DOI: http://dx.doi.org/10.7554/eLife.06914.001 PMID:26083710

Stress, Anxiety, and Immunomodulation: A Pharmacological Analysis.

PubMed

Ray, A; Gulati, K; Rai, N

2017-01-01

Stress and stressful events are common occurrences in our daily lives and such aversive situations bring about complex changes in the biological system. Such stress responses influence the brain and behavior, neuroendocrine and immune systems, and these responses orchestrate to increase or decrease the ability of the organism to cope with such stressors. The brain via expression of complex behavioral paradigms controls peripheral responses to stress and a bidirectional link exists in the modulation of stress effects. Anxiety is a common neurobehavioral correlate of a variety of stressors, and both acute and chronic stress exposure could precipitate anxiety disorders. Psychoneuroimmunology involves interactions between the brain and the immune system, and it is now being increasingly recognized that the immune system could contribute to the neurobehavioral responses to stress. Studies have shown that the brain and its complex neurotransmitter networks could influence immune function, and there could be a possible link between anxiogenesis and immunomodulation during stress. Physiological and pharmacological data have highlighted this concept, and the present review gives an overview of the relationship between stress, anxiety, and immune responsiveness. © 2017 Elsevier Inc. All rights reserved.

The neural basis of responsibility attribution in decision-making.

PubMed

Li, Peng; Shen, Yue; Sui, Xue; Chen, Changming; Feng, Tingyong; Li, Hong; Holroyd, Clay

2013-01-01

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent's emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context.

The Neural Basis of Responsibility Attribution in Decision-Making

PubMed Central

Li, Peng; Shen, Yue; Sui, Xue; Chen, Changming; Feng, Tingyong; Li, Hong; Holroyd, Clay

2013-01-01

Social responsibility links personal behavior with societal expectations and plays a key role in affecting an agent’s emotional state following a decision. However, the neural basis of responsibility attribution remains unclear. In two previous event-related brain potential (ERP) studies we found that personal responsibility modulated outcome evaluation in gambling tasks. Here we conducted a functional magnetic resonance imaging (fMRI) study to identify particular brain regions that mediate responsibility attribution. In a context involving team cooperation, participants completed a task with their teammates and on each trial received feedback about team success and individual success sequentially. We found that brain activity differed between conditions involving team success vs. team failure. Further, different brain regions were associated with reinforcement of behavior by social praise vs. monetary reward. Specifically, right temporoparietal junction (RTPJ) was associated with social pride whereas dorsal striatum and dorsal anterior cingulate cortex (ACC) were related to reinforcement of behaviors leading to personal gain. The present study provides evidence that the RTPJ is an important region for determining whether self-generated behaviors are deserving of praise in a social context. PMID:24224053

Load Modulation of BOLD Response and Connectivity Predicts Working Memory Performance in Younger and Older Adults

ERIC Educational Resources Information Center

Nagel, Irene E.; Preuschhof, Claudia; Li, Shu-Chen; Nyberg, Lars; Backman, Lars; Lindenberger, Ulman; Heekeren, Hauke R.

2011-01-01

Individual differences in working memory (WM) performance have rarely been related to individual differences in the functional responsivity of the WM brain network. By neglecting person-to-person variation, comparisons of network activity between younger and older adults using functional imaging techniques often confound differences in activity…

The Synthetic Peroxisome Proliferator-Activated Receptor-γ Agonist Ciglitazone Attenuates Neuroinflammation and Accelerates Encapsulation in Bacterial Brain Abscesses1

PubMed Central

Kielian, Tammy; Md. Syed, Mohsin; Liu, Shuliang; Phulwani, Nirmal K.; Phillips, Napoleon; Wagoner, Gail; Drew, Paul D.; Esen, Nilufer

2008-01-01

Brain abscesses result from a pyogenic parenchymal infection commonly initiated by Gram-positive bacteria such as Staphylococcus aureus. Although the host immune response elicited following infection is essential for effective bacterial containment, this response also contributes to the significant loss of brain parenchyma by necrosis that may be reduced by modulating the inflammatory response. Ciglitazone, a PPAR-γ agonist with anti-inflammatory properties, was evaluated for its ability to influence the course of brain abscess development when treatment was initiated 3 days following infection. Interestingly, abscess-associated bacterial burdens were significantly lower following ciglitazone administration, which could be explained, in part, by the finding that ciglitazone enhanced S. aureus phagocytosis by microglia. In addition, ciglitazone attenuated the expression of select inflammatory mediators during brain abscess development including inducible NO synthase, TNF-α, IL-1β, CXCL2, and CCL3. Unexpectedly, ciglitazone also accelerated brain abscess encapsulation, which was typified by the heightened expression of fibronectin and α-smooth muscle actin-positive myofibroblasts. Collectively, through its ability to attenuate excessive inflammation and accelerate abscess encapsulation, ciglitazone may effectively sequester brain abscesses and limit bacterial dissemination. PMID:18354226

Apelin targets gut contraction to control glucose metabolism via the brain.

PubMed

Fournel, Audren; Drougard, Anne; Duparc, Thibaut; Marlin, Alysson; Brierley, Stuart M; Castro, Joel; Le-Gonidec, Sophie; Masri, Bernard; Colom, André; Lucas, Alexandre; Rousset, Perrine; Cenac, Nicolas; Vergnolle, Nathalie; Valet, Philippe; Cani, Patrice D; Knauf, Claude

2017-02-01

The gut-brain axis is considered as a major regulatory checkpoint in the control of glucose homeostasis. The detection of nutrients and/or hormones in the duodenum informs the hypothalamus of the host's nutritional state. This process may occur via hypothalamic neurons modulating central release of nitric oxide (NO), which in turn controls glucose entry into tissues. The enteric nervous system (ENS) modulates intestinal contractions in response to various stimuli, but the importance of this interaction in the control of glucose homeostasis via the brain is unknown. We studied whether apelin, a bioactive peptide present in the gut, regulates ENS-evoked contractions, thereby identifying a new physiological partner in the control of glucose utilisation via the hypothalamus. We measured the effect of apelin on electrical and mechanical duodenal responses via telemetry probes and isotonic sensors in normal and obese/diabetic mice. Changes in hypothalamic NO release, in response to duodenal contraction modulated by apelin, were evaluated in real time with specific amperometric probes. Glucose utilisation in tissues was measured with orally administrated radiolabeled glucose. In normal and obese/diabetic mice, glucose utilisation is improved by the decrease of ENS/contraction activities in response to apelin, which generates an increase in hypothalamic NO release. As a consequence, glucose entry is significantly increased in the muscle. Here, we identify a novel mode of communication between the intestine and the hypothalamus that controls glucose utilisation. Moreover, our data identified oral apelin administration as a novel potential target to treat metabolic disorders. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Differential Effects of Motor Efference Copies and Proprioceptive Information on Response Evaluation Processes

PubMed Central

Stock, Ann-Kathrin; Wascher, Edmund; Beste, Christian

2013-01-01

It is well-kown that sensory information influences the way we execute motor responses. However, less is known about if and how sensory and motor information are integrated in the subsequent process of response evaluation. We used a modified Simon Task to investigate how these streams of information are integrated in response evaluation processes, applying an in-depth neurophysiological analysis of event-related potentials (ERPs), time-frequency decomposition and sLORETA. The results show that response evaluation processes are differentially modulated by afferent proprioceptive information and efference copies. While the influence of proprioceptive information is mediated via oscillations in different frequency bands, efference copy based information about the motor execution is specifically mediated via oscillations in the theta frequency band. Stages of visual perception and attention were not modulated by the interaction of proprioception and motor efference copies. Brain areas modulated by the interactive effects of proprioceptive and efference copy based information included the middle frontal gyrus and the supplementary motor area (SMA), suggesting that these areas integrate sensory information for the purpose of response evaluation. The results show how motor response evaluation processes are modulated by information about both the execution and the location of a response. PMID:23658624

Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women.

PubMed

Kullmann, Stephanie; Frank, Sabine; Heni, Martin; Ketterer, Caroline; Veit, Ralf; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

2013-01-01

There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. We performed 'resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy. Copyright © 2012 S. Karger AG, Basel.

Axonal Conduction Delays, Brain State, and Corticogeniculate Communication

PubMed Central

2017-01-01

Thalamocortical conduction times are short, but layer 6 corticothalamic axons display an enormous range of conduction times, some exceeding 40–50 ms. Here, we investigate (1) how axonal conduction times of corticogeniculate (CG) neurons are related to the visual information conveyed to the thalamus, and (2) how alert versus nonalert awake brain states affect visual processing across the spectrum of CG conduction times. In awake female Dutch-Belted rabbits, we found 58% of CG neurons to be visually responsive, and 42% to be unresponsive. All responsive CG neurons had simple, orientation-selective receptive fields, and generated sustained responses to stationary stimuli. CG axonal conduction times were strongly related to modulated firing rates (F1 values) generated by drifting grating stimuli, and their associated interspike interval distributions, suggesting a continuum of visual responsiveness spanning the spectrum of axonal conduction times. CG conduction times were also significantly related to visual response latency, contrast sensitivity (C-50 values), directional selectivity, and optimal stimulus velocity. Increasing alertness did not cause visually unresponsive CG neurons to become responsive and did not change the response linearity (F1/F0 ratios) of visually responsive CG neurons. However, for visually responsive CG neurons, increased alertness nearly doubled the modulated response amplitude to optimal visual stimulation (F1 values), significantly shortened response latency, and dramatically increased response reliability. These effects of alertness were uniform across the broad spectrum of CG axonal conduction times. SIGNIFICANCE STATEMENT Corticothalamic neurons of layer 6 send a dense feedback projection to thalamic nuclei that provide input to sensory neocortex. While sensory information reaches the cortex after brief thalamocortical axonal delays, corticothalamic axons can exhibit conduction delays of <2 ms to 40–50 ms. Here, in the corticogeniculate visual system of awake rabbits, we investigate the functional significance of this axonal diversity, and the effects of shifting alert/nonalert brain states on corticogeniculate processing. We show that axonal conduction times are strongly related to multiple visual response properties, suggesting a continuum of visual responsiveness spanning the spectrum of corticogeniculate axonal conduction times. We also show that transitions between awake brain states powerfully affect corticogeniculate processing, in some ways more strongly than in layer 4. PMID:28559382

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.

Hormonal contraceptives suppress oxytocin-induced brain reward responses to the partner's face.

PubMed

Scheele, Dirk; Plota, Jessica; Stoffel-Wagner, Birgit; Maier, Wolfgang; Hurlemann, René

2016-05-01

The hypothalamic peptide oxytocin (OXT) has been identified as a key modulator of pair-bonding in men, but its effects in women are still elusive. Moreover, there is substantial evidence that hormonal contraception (HC) influences partner preferences and sexual satisfaction, which constitute core domains of OXT function. We thus hypothesized that OXT effects on partner-related behavioral and neural responses could be significantly altered in women using HC. In this functional magnetic resonance imaging study involving 40 pair-bonded women, 21 of whom were using HC, we investigated whether a 24-IU nasal dose of OXT would modulate brain reward responses evoked by the romantic partner's face relative to the faces of familiar and unfamiliar people. Treatment with OXT increased the perceived attractiveness of the partner relative to other men, which was paralleled by elevated responses in reward-associated regions, including the nucleus accumbens. These effects of OXT were absent in women using HC. Our results confirm and extend previous findings in men that OXT interacts with the brain reward system to reinforce partner value representations, indicating a common OXT-dependent mechanism underlying partner attraction in both sexes. This mechanism may be disturbed in women using HC, suggesting that gonadal steroids could alter partner-specific OXT effects. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Using cholinergic M1 receptor positive allosteric modulators to improve memory via enhancement of brain cholinergic communication.

PubMed

Chambon, Caroline; Jatzke, Claudia; Wegener, Nico; Gravius, Andreas; Danysz, Wojciech

2012-12-15

Benzylquinolone carboxylic acid (BQCA) is a recently described cholinergic muscarinic M(1) receptor positive allosteric modulator having potential as cognitive enhancer in dementia. The present study focused on the characterisation of BQCA's mode of action in relation to positive effects on memory and side-effects in an animal model. To get insight into this mode of action, in vitro receptor potency/left shift experiments in cells stably expressing the rat's M(1) receptor were performed. They revealed an inflection point value of BQCA corresponding to 306nM, and potentiation of the agonist response up to 47-fold in presence of 10μM of BQCA. In vivo, brain microdialysis showed a maximal brain level of 270nM, 40min after i.p. administration at 10mg/kg. Based on in vitro data obtained with this dose, it can be concluded that BQCA reaches brain levels which should potentiate the agonist response about 4-fold. Behavioural data confirmed that BQCA used at 10mg/kg attenuated scopolamine-induced memory deficit in a spontaneous alternation task. Moreover, BQCA showed no side effect at 10mg/kg and above in spontaneous locomotion and salivation tests. The profile of BQCA observed in the present study displays a clear advantage over the M(1)-M(3) agonist cevimeline. The present data show the therapeutic potential of the M(1) receptor positive allosteric modulator BQCA for the treatment of memory deficits observed in Alzheimer's disease. Copyright © 2012. Published by Elsevier B.V.

Estradiol modulates neural response to conspecific and heterospecific song in female house sparrows: An in vivo positron emission tomography study

PubMed Central

Stabile, Frank A.; Carson, Richard E.

2017-01-01

Although there is growing evidence that estradiol modulates female perception of male sexual signals, relatively little research has focused on female auditory processing. We used in vivo 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging to examine the neuronal effects of estradiol and conspecific song in female house sparrows (Passer domesticus). We assessed brain glucose metabolism, a measure of neuronal activity, in females with empty implants, estradiol implants, and empty implants ~1 month after estradiol implant removal. Females were exposed to conspecific or heterospecific songs immediately prior to imaging. The activity of brain regions involved in auditory perception did not differ between females with empty implants exposed to conspecific vs. heterospecific song, but neuronal activity was significantly reduced in females with estradiol implants exposed to heterospecific song. Furthermore, our within-individual design revealed that changes in brain activity due to high estradiol were actually greater several weeks after peak hormone exposure. Overall, this study demonstrates that PET imaging is a powerful tool for assessing large-scale changes in brain activity in living songbirds, and suggests that after breeding is done, specific environmental and physiological cues are necessary for estradiol-stimulated females to lose the selectivity they display in neural response to conspecific song. PMID:28832614

The serotonin receptor 7 and the structural plasticity of brain circuits

PubMed Central

Volpicelli, Floriana; Speranza, Luisa; di Porzio, Umberto; Crispino, Marianna; Perrone-Capano, Carla

2014-01-01

Serotonin (5-hydroxytryptamine, 5-HT) modulates numerous physiological processes in the nervous system. Together with its function as neurotransmitter, 5-HT regulates neurite outgrowth, dendritic spine shape and density, growth cone motility and synapse formation during development. In the mammalian brain 5-HT innervation is virtually ubiquitous and the diversity and specificity of its signaling and function arise from at least 20 different receptors, grouped in 7 classes. Here we will focus on the role 5-HT7 receptor (5-HT7R) in the correct establishment of neuronal cytoarchitecture during development, as also suggested by its involvement in several neurodevelopmental disorders. The emerging picture shows that this receptor is a key player contributing not only to shape brain networks during development but also to remodel neuronal wiring in the mature brain, thus controlling cognitive and emotional responses. The activation of 5-HT7R might be one of the mechanisms underlying the ability of the CNS to respond to different stimuli by modulation of its circuit configuration. PMID:25309369

Prior Consumption of a Fat Meal in Healthy Adults Modulates the Brain's Response to Fat.

PubMed

Eldeghaidy, Sally; Marciani, Luca; Hort, Joanne; Hollowood, Tracey; Singh, Gulzar; Bush, Debbie; Foster, Tim; Taylor, Andy J; Busch, Johanneke; Spiller, Robin C; Gowland, Penny A; Francis, Susan T

2016-11-01

The consumption of fat is regulated by reward and homeostatic pathways, but no studies to our knowledge have examined the role of high-fat meal (HFM) intake on subsequent brain activation to oral stimuli. We evaluated how prior consumption of an HFM or water load (WL) modulates reward, homeostatic, and taste brain responses to the subsequent delivery of oral fat. A randomized 2-way crossover design spaced 1 wk apart was used to compare the prior consumption of a 250-mL HFM (520 kcal) [rapeseed oil (440 kcal), emulsifier, sucrose, flavor cocktail] or noncaloric WL on brain activation to the delivery of repeated trials of a flavored no-fat control stimulus (CS) or flavored fat stimulus (FS) in 17 healthy adults (11 men) aged 25 ± 2 y and with a body mass index (in kg/m 2 ) of 22.4 ± 0.8. We tested differences in brain activation to the CS and FS and baseline cerebral blood flow (CBF) after the HFM and WL. We also tested correlations between an individual's plasma cholecystokinin (CCK) concentration after the HFM and blood oxygenation level-dependent (BOLD) activation of brain regions. Compared to the WL, consuming the HFM led to decreased anterior insula taste activation in response to both the CS (36.3%; P < 0.05) and FS (26.5%; P < 0.05). The HFM caused reduced amygdala activation (25.1%; P < 0.01) in response to the FS compared to the CS (fat-related satiety). Baseline CBF significantly reduced in taste (insula: 5.7%; P < 0.01), homeostatic (hypothalamus: 9.2%, P < 0.01; thalamus: 5.1%, P < 0.05), and reward areas (striatum: 9.2%; P < 0.01) after the HFM. An individual's plasma CCK concentration correlated negatively with brain activation in taste and oral somatosensory (ρ = -0.39; P < 0.05) and reward areas (ρ = -0.36; P < 0.05). Our results in healthy adults show that an HFM suppresses BOLD activation in taste and reward areas compared to a WL. This understanding will help inform the reformulation of reduced-fat foods that mimic the brain's response to high-fat counterparts and guide future interventions to reduce obesity.

A single rapamycin dose protects against late-stage experimental cerebral malaria via modulation of host immunity, endothelial activation and parasite sequestration.

PubMed

Mejia, Pedro; Treviño-Villarreal, J Humberto; Reynolds, Justin S; De Niz, Mariana; Thompson, Andrew; Marti, Matthias; Mitchell, James R

2017-11-09

Maladaptive immune responses during cerebral malaria (CM) result in high mortality despite opportune anti-malarial chemotherapy. Rapamycin, an FDA-approved immunomodulator, protects against experimental cerebral malaria (ECM) in mice through effects on the host. However, the potential for reduced adaptive immunity with chronic use, combined with an incomplete understanding of mechanisms underlying protection, limit translational potential as an adjunctive therapy in CM. The results presented herein demonstrate that a single dose of rapamycin, provided as late as day 4 or 5 post-infection, protected mice from ECM neuropathology and death through modulation of distinct host responses to infection. Rapamycin prevented parasite cytoadherence in peripheral organs, including white adipose tissue, via reduction of CD36 expression. Rapamycin also altered the splenic immune response by reducing the number of activated T cells with migratory phenotype, while increasing local cytotoxic T cell activation. Finally, rapamycin reduced brain endothelial ICAM-1 expression concomitant with reduced brain pathology. Together, these changes potentially contributed to increased parasite elimination while reducing CD8 T cell migration to the brain. Rapamycin exerts pleotropic effects on host immunity, vascular activation and parasite sequestration that rescue mice from ECM, and thus support the potential clinical use of rapamycin as an adjunctive therapy in CM.

Domain expertise insulates against judgment bias by monetary favors through a modulation of ventromedial prefrontal cortex

PubMed Central

Kirk, Ulrich; Harvey, Ann; Montague, P. Read

2011-01-01

Recent work using an art-viewing paradigm shows that monetary sponsorship of the experiment by a company (a favor) increases the valuation of paintings placed next to the sponsoring corporate logo, an effect that correlates with modulation of the ventromedial prefrontal cortex (VMPFC). We used the same art-viewing paradigm to test a prevailing idea in the domain of conflict-of-interest: that expertise in a domain insulates against judgment bias even in the presence of a monetary favor. Using a cohort of art experts, we show that monetary favors do not bias the experts’ valuation of art, an effect that correlates with a lack of modulation of the VMPFC across sponsorship conditions. The lack of sponsorship effect in the VMPFC suggests the hypothesis that their brains remove the behavioral sponsorship effect by censoring sponsorship-dependent modulation of VMPFC activity. We tested the hypothesis that prefrontal regions play a regulatory role in mediating the sponsorship effect. We show that the dorsolateral prefrontal cortex (DLPFC) is recruited in the expert group. Furthermore, we tested the hypothesis in nonexpert controls by contrasting brain responses in controls who did not show a sponsorship effect to controls who did. Changes in effective connectivity between the DLPFC and VMPFC were greater in nonexpert controls, with an absence of the sponsorship effect relative to those with a presence of the sponsorship effect. The role of the DLPFC in cognitive control and emotion regulation suggests that it removes the influence of a monetary favor by controlling responses in known valuation regions of the brain including the the VMPFC. PMID:21646526

A neural network model of normal and abnormal auditory information processing.

PubMed

Du, X; Jansen, B H

2011-08-01

The ability of the brain to attenuate the response to irrelevant sensory stimulation is referred to as sensory gating. A gating deficiency has been reported in schizophrenia. To study the neural mechanisms underlying sensory gating, a neuroanatomically inspired model of auditory information processing has been developed. The mathematical model consists of lumped parameter modules representing the thalamus (TH), the thalamic reticular nucleus (TRN), auditory cortex (AC), and prefrontal cortex (PC). It was found that the membrane potential of the pyramidal cells in the PC module replicated auditory evoked potentials, recorded from the scalp of healthy individuals, in response to pure tones. Also, the model produced substantial attenuation of the response to the second of a pair of identical stimuli, just as seen in actual human experiments. We also tested the viewpoint that schizophrenia is associated with a deficit in prefrontal dopamine (DA) activity, which would lower the excitatory and inhibitory feedback gains in the AC and PC modules. Lowering these gains by less than 10% resulted in model behavior resembling the brain activity seen in schizophrenia patients, and replicated the reported gating deficits. The model suggests that the TRN plays a critical role in sensory gating, with the smaller response to a second tone arising from a reduction in inhibition of TH by the TRN. Copyright © 2011 Elsevier Ltd. All rights reserved.

Bounded Empathy: Neural Responses to Outgroup Targets’ (Mis)fortunes

PubMed Central

Cikara, Mina; Fiske, Susan T.

2013-01-01

The current study investigates whether mere stereotypes are sufficient to modulate empathic responses to other people’s (mis)fortunes, how these modulations manifest in the brain, and whether affective and neural responses relate to endorsing harm against different outgroup targets. Participants feel least bad when misfortunes befall envied targets, and worst when misfortunes befall pitied targets, as compared to ingroup targets. Participants are also least willing to endorse harming pitied targets, despite pitied targets being outgroup members. However, those participants who exhibit increased activation in functionally-defined insula/MFG when viewing pity targets experience positive events not only report feeling worse about those events, but also more willing to harm pity targets in a tradeoff scenario. Similarly, increased activation in anatomically-defined bilateral anterior insula, in response to positive events, predicts increased willingness to harm envy targets, but decreased willingness to harm ingroup targets, above and beyond self-reported affect in response to the events. Stereotypes’ specific content, and not just outgroup membership, modulates empathic responses and related behavioral consequences including harm. PMID:21671744

Acupuncture Modulates Resting State Connectivity in Default and Sensorimotor Brain Networks

PubMed Central

Dhond, Rupali P.; Yeh, Calvin; Park, Kyungmo; Kettner, Norman; Napadow, Vitaly

2008-01-01

Previous studies have defined low-frequency, spatially consistent networks in resting fMRI data which may reflect functional connectivity. We sought to explore how a complex somatosensory stimulation, acupuncture, influences intrinsic connectivity in two of these networks: the default mode network (DMN) and sensorimotor network (SMN). We analyzed resting fMRI data taken before and after verum and sham acupuncture. Electrocardiography data was used to infer autonomic modulation through measures of heart rate variability (HRV). Probabilistic independent component analysis was used to separate resting fMRI data into DMN and SMN components. Following verum, but not sham, acupuncture there was increased DMN connectivity with pain (anterior cingulate cortex (ACC), periaqueductal gray), affective (amygdala, ACC), and memory (hippocampal formation, middle temporal gyrus) related brain regions. Furthermore, increased DMN connectivity with the hippocampal formation, a region known to support memory and interconnected with autonomic brain regions, was negatively correlated with acupuncture-induced increase in a sympathetic related HRV metric (LFu), and positively correlated with a parasympathetic related metric (HFu). Following verum, but not sham, acupuncture there was also increased SMN connectivity with pain related brain regions (ACC, cerebellum). We attribute differences between verum and sham acupuncture to more varied and stronger sensations evoked by verum acupuncture. Our results demonstrate for the first time that acupuncture can enhance the post-stimulation spatial extent of resting brain networks to include anti-nociceptive, memory, and affective brain regions. This modulation and sympathovagal response may relate to acupuncture analgesia and other potential therapeutic effects. PMID:18337009

Low tryptophan diet decreases brain serotonin and alters response to apomorphine

NASA Technical Reports Server (NTRS)

Sahakian, B. J.; Wurtman, R. J.; Barr, J. K.; Millington, W. R.; Chiel, H. J.

1979-01-01

The role of the serotoninergic system in the regulation of apomorphine-induced behavior, a behavior primarily controlled by dopaminergic neurotransmission, was investigated in rats fed on a low tryptophan diet since weaning. It was found that reductions in brain seritonin (5-HT) produced by diet result in decreased stereotypy after apomorphine administration. This indicates that although stereotyped behavior is primarily mediated by dopaminergic mechanisms, it can also be modulated by other neurotransmitter including 5-HT. It was also shown that changes in brain seritonin levels can affect psychomotor stimulant-induced hypothermia.

Thalamocortical Oscillations in the Sleeping and Aroused Brain

NASA Astrophysics Data System (ADS)

Steriade, Mircea; McCormick, David A.; Sejnowski, Terrence J.

1993-10-01

Sleep is characterized by synchronized events in billions of synaptically coupled neurons in thalamocortical systems. The activation of a series of neuromodulatory transmitter systems during awakening blocks low-frequency oscillations, induces fast rhythms, and allows the brain to recover full responsiveness. Analysis of cortical and thalamic networks at many levels, from molecules to single neurons to large neuronal assemblies, with a variety of techniques, ranging from intracellular recordings in vivo and in vitro to computer simulations, is beginning to yield insights into the mechanisms of the generation, modulation, and function of brain oscillations.

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."

Adolescents growing up amidst intractable conflict attenuate brain response to pain of outgroup.

PubMed

Levy, Jonathan; Goldstein, Abraham; Influs, Moran; Masalha, Shafiq; Zagoory-Sharon, Orna; Feldman, Ruth

2016-11-29

Adolescents' participation in intergroup conflicts comprises an imminent global risk, and understanding its neural underpinnings may open new perspectives. We assessed Jewish-Israeli and Arab-Palestinian adolescents for brain response to the pain of ingroup/outgroup protagonists using magnetoencephalography (MEG), one-on-one positive and conflictual interactions with an outgroup member, attitudes toward the regional conflict, and oxytocin levels. A neural marker of ingroup bias emerged, expressed via alpha modulations in the somatosensory cortex (S1) that characterized an automatic response to the pain of all protagonists followed by rebound/enhancement to ingroup pain only. Adolescents' hostile social interactions with outgroup members and uncompromising attitudes toward the conflict influenced this neural marker. Furthermore, higher oxytocin levels in the Jewish-Israeli majority and tighter brain-to-brain synchrony among group members in the Arab-Palestinian minority enhanced the neural ingroup bias. Findings suggest that in cases of intractable intergroup conflict, top-down control mechanisms may block the brain's evolutionary-ancient resonance to outgroup pain, pinpointing adolescents' interpersonal and sociocognitive processes as potential targets for intervention.

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.

Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior

PubMed Central

Picciotto, Marina R.; Higley, Michael J.; Mineur, Yann S.

2012-01-01

Acetylcholine in the brain alters neuronal excitability, influences synaptic transmission, induces synaptic plasticity and coordinates the firing of groups of neurons. As a result, it changes the state of neuronal networks throughout the brain and modifies their response to internal and external inputs: the classical role of a neuromodulator. Here we identify actions of cholinergic signaling on cellular and synaptic properties of neurons in several brain areas and discuss the consequences of this signaling on behaviors related to drug abuse, attention, food intake, and affect. The diverse effects of acetylcholine depend on the site of release, the receptor subtypes, and the target neuronal population, however, a common theme is that acetylcholine potentiates behaviors that are adaptive to environmental stimuli and decreases responses to ongoing stimuli that do not require immediate action. The ability of acetylcholine to coordinate the response of neuronal networks in many brain areas makes cholinergic modulation an essential mechanism underlying complex behaviors. PMID:23040810

Parametric Modulation of Error-Related ERP Components by the Magnitude of Visuo-Motor Mismatch

ERIC Educational Resources Information Center

Vocat, Roland; Pourtois, Gilles; Vuilleumier, Patrik

2011-01-01

Errors generate typical brain responses, characterized by two successive event-related potentials (ERP) following incorrect action: the error-related negativity (ERN) and the positivity error (Pe). However, it is unclear whether these error-related responses are sensitive to the magnitude of the error, or instead show all-or-none effects. We…

Uncoupling primer and releaser responses to pheromone in honey bees

NASA Astrophysics Data System (ADS)

Grozinger, Christina M.; Fischer, Patrick; Hampton, Jacob E.

2007-05-01

Pheromones produce dramatic behavioral and physiological responses in a wide variety of species. Releaser pheromones elicit rapid responses within seconds or minutes, while primer pheromones produce long-term changes which may take days to manifest. Honeybee queen mandibular pheromone (QMP) elicits multiple distinct behavioral and physiological responses in worker bees, as both a releaser and primer, and thus produces responses on vastly different time scales. In this study, we demonstrate that releaser and primer responses to QMP can be uncoupled. First, treatment with the juvenile hormone analog methoprene leaves a releaser response (attraction to QMP) intact, but modulates QMP’s primer effects on sucrose responsiveness. Secondly, two components of QMP (9-ODA and 9-HDA) do not elicit a releaser response (attraction) but are as effective as QMP at modulating a primer response, downregulation of foraging-related brain gene expression. These results suggest that different responses to a single pheromone may be produced via distinct pathways.

Relationship between Parental Feeding Practices and Neural Responses to Food Cues in Adolescents

PubMed Central

Chambers, Alison; Blissett, Jacqueline; Chechlacz, Magdalena; Barrett, Timothy; Higgs, Suzanne; Nouwen, Arie

2016-01-01

Social context, specifically within the family, influences adolescent eating behaviours and thus their health. Little is known about the specific mechanisms underlying the effects of parental feeding practices on eating. We explored relationships between parental feeding practices and adolescent eating habits and brain activity in response to viewing food images. Fifty- seven adolescents (15 with type 2 diabetes mellitus, 21 obese and 21 healthy weight controls) underwent fMRI scanning whilst viewing images of food or matched control images. Participants completed the Kids Child Feeding Questionnaire, the Childrens’ Dutch Eating Behaviour Questionnaire (DEBQ) and took part in an observed meal. Parents completed the Comprehensive Feeding Practices Questionniare and the DEBQ. We were particularly interested in brain activity in response to food cues that was modulated by different feeding and eating styles. Healthy-weight participants increased activation (compared to the other groups) to food in proportion to the level of parental restriction in visual areas of the brain such as right lateral occipital cortex (LOC), right temporal occipital cortex, left occipital fusiform gyrus, left lateral and superior LOC. Adolescents with type 2 diabetes mellitus had higher activation (compared to the other groups) with increased parental restrictive feeding in areas relating to emotional control, attention and decision-making, such as posterior cingulate, precuneus, frontal operculum and right middle frontal gyrus. Participants with type 2 diabetes mellitus also showed higher activation (compared to the other groups) in the left anterior intraparietal sulcus and angular gyrus when they also reported higher self restraint. Parental restriction did not modulate food responses in obese participants, but there was increased activity in visual (visual cortex, left LOC, left occipital fusiform gyrus) and reward related brain areas (thalamus and parietal operculum) in response to parental teaching and modelling of behaviour. Parental restrictive feeding and parental teaching and modelling affected neural responses to food cues in different ways, depending on motivations and diagnoses, illustrating a social influence on neural responses to food cues. PMID:27479051

Relationship between Parental Feeding Practices and Neural Responses to Food Cues in Adolescents.

PubMed

Allen, Harriet A; Chambers, Alison; Blissett, Jacqueline; Chechlacz, Magdalena; Barrett, Timothy; Higgs, Suzanne; Nouwen, Arie

2016-01-01

Social context, specifically within the family, influences adolescent eating behaviours and thus their health. Little is known about the specific mechanisms underlying the effects of parental feeding practices on eating. We explored relationships between parental feeding practices and adolescent eating habits and brain activity in response to viewing food images. Fifty- seven adolescents (15 with type 2 diabetes mellitus, 21 obese and 21 healthy weight controls) underwent fMRI scanning whilst viewing images of food or matched control images. Participants completed the Kids Child Feeding Questionnaire, the Childrens' Dutch Eating Behaviour Questionnaire (DEBQ) and took part in an observed meal. Parents completed the Comprehensive Feeding Practices Questionniare and the DEBQ. We were particularly interested in brain activity in response to food cues that was modulated by different feeding and eating styles. Healthy-weight participants increased activation (compared to the other groups) to food in proportion to the level of parental restriction in visual areas of the brain such as right lateral occipital cortex (LOC), right temporal occipital cortex, left occipital fusiform gyrus, left lateral and superior LOC. Adolescents with type 2 diabetes mellitus had higher activation (compared to the other groups) with increased parental restrictive feeding in areas relating to emotional control, attention and decision-making, such as posterior cingulate, precuneus, frontal operculum and right middle frontal gyrus. Participants with type 2 diabetes mellitus also showed higher activation (compared to the other groups) in the left anterior intraparietal sulcus and angular gyrus when they also reported higher self restraint. Parental restriction did not modulate food responses in obese participants, but there was increased activity in visual (visual cortex, left LOC, left occipital fusiform gyrus) and reward related brain areas (thalamus and parietal operculum) in response to parental teaching and modelling of behaviour. Parental restrictive feeding and parental teaching and modelling affected neural responses to food cues in different ways, depending on motivations and diagnoses, illustrating a social influence on neural responses to food cues.

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

PubMed Central

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

2012-01-01

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

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

Changes in predictive cuing modulate the hemispheric distribution of the P1 inhibitory response to attentional targets.

PubMed

Lasaponara, Stefano; D' Onofrio, Marianna; Dragone, Alessio; Pinto, Mario; Caratelli, Ludovica; Doricchi, Fabrizio

2017-05-01

Brain activity related to orienting of attention with spatial cues and brain responses to attentional targets are influenced the probabilistic contingency between cues and targets. Compared to predictive cues, cues predicting at chance the location of targets reduce the filtering out of uncued locations and the costs in reorienting attention to targets presented at these locations. Slagter et al. (2016) have recently suggested that the larger target related P1 component that is found in the hemisphere ipsilateral to validly cued targets reflects stimulus-driven inhibition in the processing of the unstimulated side of space contralateral to the same hemisphere. Here we verified whether the strength of this inhibition and the amplitude of the corresponding P1 wave are modulated by the probabilistic link between cues and targets. Healthy participants performed a task of endogenous orienting once with predictive and once with non-predictive directional cues. In the non-predictive condition we observed a drop in the amplitude of the P1 ipsilateral to the target and in the costs of reorienting. No change in the inter-hemispheric latencies of the P1 was found between the two predictive conditions. The N1 facilitatory component was unaffected by predictive cuing. These results show that the predictive context modulates the strength of the inhibitory P1 response and that this modulation is not matched with changes in the inter-hemispheric interaction between the P1 generators of the two hemispheres. Copyright © 2017. Published by Elsevier Ltd.

The role of the Drosophila lateral horn in olfactory information processing and behavioral response.

PubMed

Schultzhaus, Janna N; Saleem, Sehresh; Iftikhar, Hina; Carney, Ginger E

2017-04-01

Animals must rapidly and accurately process environmental information to produce the correct behavioral responses. Reactions to previously encountered as well as to novel but biologically important stimuli are equally important, and one understudied region in the insect brain plays a role in processing both types of stimuli. The lateral horn is a higher order processing center that mainly processes olfactory information and is linked via olfactory projection neurons to another higher order learning center, the mushroom body. This review focuses on the lateral horn of Drosophila where most functional studies have been performed. We discuss connectivity between the primary olfactory center, the antennal lobe, and the lateral horn and mushroom body. We also present evidence for the lateral horn playing roles in innate behavioral responses by encoding biological valence to novel odor cues and in learned responses to previously encountered odors by modulating neural activity within the mushroom body. We describe how these processes contribute to acceptance or avoidance of appropriate or inappropriate mates and food, as well as the identification of predators. The lateral horn is a sexually dimorphic and plastic region of the brain that modulates other regions of the brain to ensure that insects produce rapid and effective behavioral responses to both novel and learned stimuli, yet multiple gaps exist in our knowledge of this important center. We anticipate that future studies on olfactory processing, learning, and innate behavioral responses will include the lateral horn in their examinations, leading to a more comprehensive understanding of olfactory information relay and resulting behaviors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modulation and transmission of sweet taste information for energy homeostasis.

PubMed

Sanematsu, Keisuke; Horio, Nao; Murata, Yoshihiro; Yoshida, Ryusuke; Ohkuri, Tadahiro; Shigemura, Noriatsu; Ninomiya, Yuzo

2009-07-01

Perception of sweet taste is important for animals to detect external energy source of calories. In mice, sweet-sensitive cells possess a leptin receptor. Increase of plasma leptin with increasing internal energy storage in the adipose tissue suppresses sweet taste responses via this receptor. Data from our recent studies indicate that leptin may also modulate sweet taste sensation in humans with a diurnal variation in sweet sensitivity. This leptin modulation of sweet taste information to the brain may influence individuals' preference and ingestive behavior, thereby playing important roles in regulation of energy homeostasis.

Aggression differentially modulates brain responses to fearful and angry faces: an exploratory study.

PubMed

Lu, Hui; Wang, Yu; Xu, Shuang; Wang, Yifeng; Zhang, Ruiping; Li, Tsingan

2015-08-19

Aggression is reported to modulate neural responses to the threatening information. However, whether aggression can modulate neural response to different kinds of threatening facial expressions (angry and fearful expressions) remains unknown. Thus, event-related potentials were measured in individuals (13 high aggressive, 12 low aggressive) exposed to neutral, angry, and fearful facial expressions while performing a frame-distinguishing task, irrespective of the emotional valence of the expressions. Highly aggressive participants showed no distinct neural responses between the three facial expressions. In addition, compared with individuals with low aggression, highly aggressive individuals showed a decreased frontocentral response to fearful faces within 250-300 ms and to angry faces within 400-500 ms of exposure. These results indicate that fearful faces represent a more threatening signal requiring a quick cognitive response during the early stage of facial processing, whereas angry faces elicit a stronger response during the later processing stage because of its eminent emotional significance. The present results represent the first known evidence that aggression is associated with different neural responses to fearful and angry faces. By exploring the distinct temporal responses to fearful and angry faces modulated by aggression, this study more precisely characterizes the cognitive characteristics of aggressive individuals. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.

Extrathalamic Modulation of Cortical Responsiveness

DTIC Science & Technology

1994-08-01

1988). McEntee, W. J. & Mair, R. G. (1990). The Korsakoff syndrome : a Clonidine improves memory function in schizophrenia indepen- neurochemical...cognition and putati% e neurotransmitters on neuronal activity in monkey auditory rCBF in Korsakoffs psychosis. Psychological Medicine (in the cortw. Brain

The Synapse Project: Engagement in mentally challenging activities enhances neural efficiency.

PubMed

McDonough, Ian M; Haber, Sara; Bischof, Gérard N; Park, Denise C

2015-01-01

Correlational and limited experimental evidence suggests that an engaged lifestyle is associated with the maintenance of cognitive vitality in old age. However, the mechanisms underlying these engagement effects are poorly understood. We hypothesized that mental effort underlies engagement effects and used fMRI to examine the impact of high-challenge activities (digital photography and quilting) compared with low-challenge activities (socializing or performing low-challenge cognitive tasks) on neural function at pretest, posttest, and one year after the engagement program. In the scanner, participants performed a semantic-classification task with two levels of difficulty to assess the modulation of brain activity in response to task demands. The High-Challenge group, but not the Low-Challenge group, showed increased modulation of brain activity in medial frontal, lateral temporal, and parietal cortex-regions associated with attention and semantic processing-some of which were maintained a year later. This increased modulation stemmed from decreases in brain activity during the easy condition for the High-Challenge group and was associated with time committed to the program, age, and cognition. Sustained engagement in cognitively demanding activities facilitated cognition by increasing neural efficiency. Mentally-challenging activities may be neuroprotective and an important element to maintaining a healthy brain into late adulthood.

The Synapse Project: Engagement in mentally challenging activities enhances neural efficiency

PubMed Central

McDonough, Ian M.; Haber, Sara; Bischof, Gérard N.; Park, Denise C.

2015-01-01

Purpose: Correlational and limited experimental evidence suggests that an engaged lifestyle is associated with the maintenance of cognitive vitality in old age. However, the mechanisms underlying these engagement effects are poorly understood. We hypothesized that mental effort underlies engagement effects and used fMRI to examine the impact of high-challenge activities (digital photography and quilting) compared with low-challenge activities (socializing or performing low-challenge cognitive tasks) on neural function at pretest, posttest, and one year after the engagement program. Methods: In the scanner, participants performed a semantic-classification task with two levels of difficulty to assess the modulation of brain activity in response to task demands. Results: The High-Challenge group, but not the Low-Challenge group, showed increased modulation of brain activity in medial frontal, lateral temporal, and parietal cortex—regions associated with attention and semantic processing—some of which were maintained a year later. This increased modulation stemmed from decreases in brain activity during the easy condition for the High-Challenge group and was associated with time committed to the program, age, and cognition. Conclusions: Sustained engagement in cognitively demanding activities facilitated cognition by increasing neural efficiency. Mentally-challenging activities may be neuroprotective and an important element to maintaining a healthy brain into late adulthood. PMID:26484698

Estradiol-dependent modulation of auditory processing and selectivity in songbirds

PubMed Central

Maney, Donna; Pinaud, Raphael

2011-01-01

The steroid hormone estradiol plays an important role in reproductive development and behavior and modulates a wide array of physiological and cognitive processes. Recently, reports from several research groups have converged to show that estradiol also powerfully modulates sensory processing, specifically, the physiology of central auditory circuits in songbirds. These investigators have discovered that (1) behaviorally-relevant auditory experience rapidly increases estradiol levels in the auditory forebrain; (2) estradiol instantaneously enhances the responsiveness and coding efficiency of auditory neurons; (3) these changes are mediated by a non-genomic effect of brain-generated estradiol on the strength of inhibitory neurotransmission; and (4) estradiol regulates biochemical cascades that induce the expression of genes involved in synaptic plasticity. Together, these findings have established estradiol as a central regulator of auditory function and intensified the need to consider brain-based mechanisms, in addition to peripheral organ dysfunction, in hearing pathologies associated with estrogen deficiency. PMID:21146556

Temporal resolution of the Florida manatee (Trichechus manatus latirostris) auditory system.

PubMed

Mann, David A; Colbert, Debborah E; Gaspard, Joseph C; Casper, Brandon M; Cook, Mandy L H; Reep, Roger L; Bauer, Gordon B

2005-10-01

Auditory evoked potential (AEP) measurements of two Florida manatees (Trichechus manatus latirostris) were measured in response to amplitude modulated tones. The AEP measurements showed weak responses to test stimuli from 4 kHz to 40 kHz. The manatee modulation rate transfer function (MRTF) is maximally sensitive to 150 and 600 Hz amplitude modulation (AM) rates. The 600 Hz AM rate is midway between the AM sensitivities of terrestrial mammals (chinchillas, gerbils, and humans) (80-150 Hz) and dolphins (1,000-1,200 Hz). Audiograms estimated from the input-output functions of the EPs greatly underestimate behavioral hearing thresholds measured in two other manatees. This underestimation is probably due to the electrodes being located several centimeters from the brain.

Motivational orientation modulates the neural response to reward.

PubMed

Linke, Julia; Kirsch, Peter; King, Andrea V; Gass, Achim; Hennerici, Michael G; Bongers, André; Wessa, Michèle

2010-02-01

Motivational orientation defines the source of motivation for an individual to perform a particular action and can either originate from internal desires (e.g., interest) or external compensation (e.g., money). To this end, motivational orientation should influence the way positive or negative feedback is processed during learning situations and this might in turn have an impact on the learning process. In the present study, we thus investigated whether motivational orientation, i.e., extrinsic and intrinsic motivation modulates the neural response to reward and punishment as well as learning from reward and punishment in 33 healthy individuals. To assess neural responses to reward, punishment and learning of reward contingencies we employed a probabilistic reversal learning task during functional magnetic resonance imaging. Extrinsic and intrinsic motivation were assessed with a self-report questionnaire. Rewarding trials fostered activation in the medial orbitofrontal cortex and anterior cingulate gyrus (ACC) as well as the amygdala and nucleus accumbens, whereas for punishment an increased neural response was observed in the medial and inferior prefrontal cortex, the superior parietal cortex and the insula. High extrinsic motivation was positively correlated to increased neural responses to reward in the ACC, amygdala and putamen, whereas a negative relationship between intrinsic motivation and brain activation in these brain regions was observed. These findings show that motivational orientation indeed modulates the responsiveness to reward delivery in major components of the human reward system and therefore extends previous results showing a significant influence of individual differences in reward-related personality traits on the neural processing of reward. Copyright (c) 2009 Elsevier Inc. All rights reserved.

BDNF and AMPA receptors in the cNTS modulate the hyperglycemic reflex after local carotid body NaCN stimulation.

PubMed

Cuéllar, R; Montero, S; Luquín, S; García-Estrada, J; Melnikov, V; Virgen-Ortiz, A; Lemus, M; Pineda-Lemus, M; de Álvarez-Buylla, E

2017-07-01

The application of sodium cyanide (NaCN) to the carotid body receptors (CBR) (CBR stimulation) induces rapid blood hyperglycemia and an increase in brain glucose retention. The commissural nucleus tractus solitarius (cNTS) is an essential relay nucleus in this hyperglycemic reflex; it receives glutamatergic afferents (that also release brain derived neurotrophic factor, BDNF) from the nodose-petrosal ganglia that relays CBR information. Previous work showed that AMPA in NTS blocks hyperglycemia and brain glucose retention after CBR stimulation. In contrast, BDNF, which attenuates glutamatergic AMPA currents in NTS, enhances these glycemic responses. Here we investigated the combined effects of BDNF and AMPA (and their antagonists) in NTS on the glycemic responses to CBR stimulation. Microinjections of BDNF plus AMPA into the cNTS before CBR stimulation in anesthetized rats, induced blood hyperglycemia and an increase in brain arteriovenous (a-v) of blood glucose concentration difference, which we infer is due to increased brain glucose retention. By contrast, the microinjection of the TrkB antagonist K252a plus AMPA abolished the glycemic responses to CBR stimulation similar to what is observed after AMPA pretreatments. In BDNF plus AMPA microinjections preceding CBR stimulation, the number of c-fos immunoreactive cNTS neurons increased. In contrast, in the rats microinjected with K252a plus AMPA in NTS, before CBR stimulation, c-fos expression in cNTS decreased. The expression of AMPA receptors GluR2/3 did not change in any of the studied groups. These results indicate that BDNF in cNTS plays a key role in the modulation of the hyperglycemic reflex initiated by CBR stimulation. Copyright © 2017. Published by Elsevier B.V.

Acute pharmacologically induced shifts in serotonin availability abolish emotion-selective responses to negative face emotions in distinct brain networks.

PubMed

Grady, Cheryl L; Siebner, Hartwig R; Hornboll, Bettina; Macoveanu, Julian; Paulson, Olaf B; Knudsen, Gitte M

2013-05-01

Pharmacological manipulation of serotonin availability can alter the processing of facial expressions of emotion. Using a within-subject design, we measured the effect of serotonin on the brain's response to aversive face emotions with functional MRI while 20 participants judged the gender of neutral, fearful and angry faces. In three separate and counterbalanced sessions, participants received citalopram (CIT) to raise serotonin levels, underwent acute tryptophan depletion (ATD) to lower serotonin, or were studied without pharmacological challenge (Control). An analysis designed to identify distributed brain responses identified two brain networks with modulations of activity related to face emotion and serotonin level. The first network included the left amygdala, bilateral striatum, and fusiform gyri. During the Control session this network responded only to fearful faces; increasing serotonin decreased this response to fear, whereas reducing serotonin enhanced the response of this network to angry faces. The second network involved bilateral amygdala and ventrolateral prefrontal cortex, and these regions also showed increased activity to fear during the Control session. Both drug challenges enhanced the neural response of this set of regions to angry faces, relative to Control, and CIT also enhanced activity for neutral faces. The net effect of these changes in both networks was to abolish the selective response to fearful expressions. These results suggest that a normal level of serotonin is critical for maintaining a differentiated brain response to threatening face emotions. Lower serotonin leads to a broadening of a normally fear-specific response to anger, and higher levels reduce the differentiated brain response to aversive face emotions. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

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.

Relevance of chronic stress and the two faces of microglia in Parkinson’s disease

PubMed Central

Herrera, Antonio J.; Espinosa-Oliva, Ana M.; Carrillo-Jiménez, Alejandro; Oliva-Martín, María J.; García-Revilla, Juan; García-Quintanilla, Alberto; de Pablos, Rocío M.; Venero, José L.

2015-01-01

This review is aimed to highlight the importance of stress and glucocorticoids (GCs) in modulating the inflammatory response of brain microglia and hence its potential involvement in Parkinson’s disease (PD). The role of inflammation in PD has been reviewed extensively in the literature and it is supposed to play a key role in the course of the disease. Historically, GCs have been strongly associated as anti-inflammatory hormones. However, accumulating evidence from the peripheral and central nervous system have clearly revealed that, under specific conditions, GCs may promote brain inflammation including pro-inflammatory activation of microglia. We have summarized relevant data linking PD, neuroinflamamation and chronic stress. The timing and duration of stress response may be critical for delineating an immune response in the brain thus probably explain the dual role of GCs and/or chronic stress in different animal models of PD. PMID:26321913

Sex differences in directional brain responses to infant hunger cries.

PubMed

De Pisapia, Nicola; Bornstein, Marc H; Rigo, Paola; Esposito, Gianluca; De Falco, Simona; Venuti, Paola

2013-02-13

Infant cries are a critical survival mechanism that draw the attention of adult caregivers, who can then satisfy the basic needs of otherwise helpless infants. Here, we used functional neuroimaging to determine the effects of infant hunger cries on the brain activity of adults who were in a cognitively nondemanding mental state of awake rest. We found that the brains of men and women, independent of parental status (parent or nonparent), reacted differently to infant cries. Specifically, the dorsal medial prefrontal and posterior cingulate areas, known to be involved in mind wandering (the stream of thought typical of awake rest), remained active in men during exposure to infant cries, whereas in women, activity in these regions decreased. These results show sex-dependent modulation of brain responses to infant requests to be fed, and specifically, they indicate that women interrupt mind wandering when exposed to the sounds of infant hunger cries, whereas men carry on without interruption.

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

PubMed

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

2014-03-19

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 systematically reveal the functional architecture of neural circuits underlying a sensorimotor behavior in a vertebrate brain. Copyright © 2014 Elsevier Inc. All rights reserved.

Envelope Responses in Single-Trial EEG Indicate Attended Speaker in a Cocktail Party

DTIC Science & Technology

2013-06-20

users to modulate their brain activity, such as motor rhythms, in order to signal intent [13], but these often require considerable training . Other...BCIs forgo training and instead have subjects make choices by attending to one of multiple visual and/or auditory stimuli. By presenting each stimulus...modulated). An envelope-based BCI could operate on more naturalistic auditory stimuli, such as speech or music . For example, an envelope-based BCI

Brain mast cells link the immune system to anxiety-like behavior

PubMed Central

Nautiyal, Katherine M.; Ribeiro, Ana C.; Pfaff, Donald W.; Silver, Rae

2008-01-01

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links. PMID:19004805

Brain mast cells link the immune system to anxiety-like behavior.

PubMed

Nautiyal, Katherine M; Ribeiro, Ana C; Pfaff, Donald W; Silver, Rae

2008-11-18

Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient Kit(W-sh/W-sh) (sash(-/-)) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links.

Brain foods: the effects of nutrients on brain function

PubMed Central

Gómez-Pinilla, Fernando

2009-01-01

It has long been suspected that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that are responsible for the action of diet on brain health and mental function. Several gut hormones that can enter the brain, or that are produced in the brain itself, influence cognitive ability. In addition, well-established regulators of synaptic plasticity, such as brain-derived neurotrophic factor, can function as metabolic modulators, responding to peripheral signals such as food intake. Understanding the molecular basis of the effects of food on cognition will help us to determine how best to manipulate diet in order to increase the resistance of neurons to insults and promote mental fitness. PMID:18568016

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.

Effective connectivity of ascending and descending frontal-thalamic pathways during sustained attention: Complex brain network interactions in adolescence

PubMed Central

Jagtap, Pranav; Diwadkar, Vaibhav A.

2016-01-01

Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals (Dynamic Causal Modeling; DCM) to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectures were employed in DCM to evaluate hypotheses on bilateral frontal-thalamic connections and their modulation by attention demand, selected at a second level using Bayesian Model Selection. The model architecture evinced significant contextual modulation by attention of ascending (thalamus → dPFC) and descending (dPFC → thalamus) pathways. However, modulation of these pathways was asymmetric: While positive modulation of the ascending pathway was comparable across attention demand, modulation of the descending pathway was significantly greater when attention demands were increased. Increased modulation of the (dPFC → thalamus) pathway in response to increased attention demand constitutes novel evidence of attention-related gain in the connectivity of the descending attention pathway. By comparison demand-independent modulation of the ascending (thalamus → dPFC) pathway suggests unbiased thalamic inputs to the cortex in the context of the paradigm. PMID:27145923

Attention modulates the dorsal striatum response to love stimuli.

PubMed

Langeslag, Sandra J E; van der Veen, Frederik M; Röder, Christian H

2014-02-01

In previous functional magnetic resonance imaging (fMRI) studies concerning romantic love, several brain regions including the caudate and putamen have consistently been found to be more responsive to beloved-related than control stimuli. In those studies, infatuated individuals were typically instructed to passively view the stimuli or to think of the viewed person. In the current study, we examined how the instruction to attend to, or ignore the beloved modulates the response of these brain areas. Infatuated individuals performed an oddball task in which pictures of their beloved and friend served as targets and distractors. The dorsal striatum showed greater activation for the beloved than friend, but only when they were targets. The dorsal striatum actually tended to show less activation for the beloved than the friend when they were distractors. The longer the love and relationship duration, the smaller the response of the dorsal striatum to beloved-distractor stimuli was. We interpret our findings in terms of reinforcement learning. By virtue of using a cognitive task with a full factorial design, we show that the dorsal striatum is not activated by beloved-related information per se, but only by beloved-related information that is attended. Copyright © 2012 Wiley Periodicals, Inc.

Glycine Receptor Activation Impairs ATP-Induced Calcium Transients in Cultured Cortical Astrocytes

PubMed Central

Morais, Tatiana P.; Coelho, David; Vaz, Sandra H.; Sebastião, Ana M.; Valente, Cláudia A.

2018-01-01

In central nervous system, glycine receptor (GlyR) is mostly expressed in the spinal cord and brainstem, but glycinergic transmission related elements have also been identified in the brain. Astrocytes are active elements at the tripartite synapse, being responsible for the maintenance of brain homeostasis and for the fine-tuning of synaptic activity. These cells communicate, spontaneously or in response to a stimulus, by elevations in their cytosolic calcium (calcium transients, Ca2+T) that can be propagated to other cells. How these Ca2+T are negatively modulated is yet poorly understood. In this work, we evaluated GlyR expression and its role on calcium signaling modulation in rat brain astrocytes. We first proved that GlyR, predominantly subunits α2 and β, was expressed in brain astrocytes and its localization was confirmed in the cytoplasm and astrocytic processes by immunohistochemistry assays. Calcium imaging experiments in cultured astrocytes showed that glycine (500 μM), a GlyR agonist, caused a concentration-dependent reduction in ATP-induced Ca2+T, an effect abolished by the GlyR antagonist, strychnine (0.8 μM), as well as by nocodazole (1 μM), known to impair GlyR anchorage to the plasma membrane. This effect was mimicked by activation of GABAAR, another Cl--permeable channel. In summary, we demonstrated that GlyR activation in astrocytes mediates an inhibitory effect upon ATP induced Ca2+T, which most probably involves changes in membrane permeability to Cl- and requires GlyR anchorage at the plasma membrane. GlyR in astrocytes may thus be part of a mechanism to modulate astrocyte-to-neuron communication. PMID:29386993

Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke.

PubMed

Li, Ming-Hua; Leng, Tian-Dong; Feng, Xue-Chao; Yang, Tao; Simon, Roger P; Xiong, Zhi-Gang

2016-08-26

An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Citicoline Affects Appetite and Cortico-Limbic Responses to Images of High Calorie Foods

PubMed Central

Killgore, William D. S.; Ross, Amy J.; Kamiya, Toshi; Kawada, Yoko; Renshaw, Perry F.; Yurgelun-Todd, Deborah A.

2011-01-01

Cytidine-5’-diphosphocholine (citicoline) has a variety of cognitive enhancing, neuroprotective, and neuroregenerative properties. In cocaine-addicted individuals, citicoline has been shown to increase brain dopamine levels and reduce cravings. The effects of this compound on appetite, food cravings, and brain responses to food are unknown. We compared the effects of treatment with citicoline (500 mg/day versus 2000 mg/day) for six weeks on changes in appetite ratings, weight, and cortico-limbic responses to images of high calorie foods using functional magnetic resonance imaging (fMRI). After six weeks, there was no significant change in weight status, although significant declines in appetite ratings were observed for the 2000 mg/day group. The higher dose group also showed significant increases in functional brain responses to food stimuli within the amygdala, insula, and lateral orbitofrontal cortex. Increased activation in these regions correlated with declines in appetite ratings. These preliminary findings suggest a potential usefulness of citicoline in modulating appetite, but further research is warranted. PMID:19260039

Conflict Resolution as Near-Threshold Decision-Making: A Spiking Neural Circuit Model with Two-Stage Competition for Antisaccadic Task

PubMed Central

Wang, Xiao-Jing

2016-01-01

Automatic responses enable us to react quickly and effortlessly, but they often need to be inhibited so that an alternative, voluntary action can take place. To investigate the brain mechanism of controlled behavior, we investigated a biologically-based network model of spiking neurons for inhibitory control. In contrast to a simple race between pro- versus anti-response, our model incorporates a sensorimotor remapping module, and an action-selection module endowed with a “Stop” process through tonic inhibition. Both are under the modulation of rule-dependent control. We tested the model by applying it to the well known antisaccade task in which one must suppress the urge to look toward a visual target that suddenly appears, and shift the gaze diametrically away from the target instead. We found that the two-stage competition is crucial for reproducing the complex behavior and neuronal activity observed in the antisaccade task across multiple brain regions. Notably, our model demonstrates two types of errors: fast and slow. Fast errors result from failing to inhibit the quick automatic responses and therefore exhibit very short response times. Slow errors, in contrast, are due to incorrect decisions in the remapping process and exhibit long response times comparable to those of correct antisaccade responses. The model thus reveals a circuit mechanism for the empirically observed slow errors and broad distributions of erroneous response times in antisaccade. Our work suggests that selecting between competing automatic and voluntary actions in behavioral control can be understood in terms of near-threshold decision-making, sharing a common recurrent (attractor) neural circuit mechanism with discrimination in perception. PMID:27551824

Conflict Resolution as Near-Threshold Decision-Making: A Spiking Neural Circuit Model with Two-Stage Competition for Antisaccadic Task.

PubMed

Lo, Chung-Chuan; Wang, Xiao-Jing

2016-08-01

Automatic responses enable us to react quickly and effortlessly, but they often need to be inhibited so that an alternative, voluntary action can take place. To investigate the brain mechanism of controlled behavior, we investigated a biologically-based network model of spiking neurons for inhibitory control. In contrast to a simple race between pro- versus anti-response, our model incorporates a sensorimotor remapping module, and an action-selection module endowed with a "Stop" process through tonic inhibition. Both are under the modulation of rule-dependent control. We tested the model by applying it to the well known antisaccade task in which one must suppress the urge to look toward a visual target that suddenly appears, and shift the gaze diametrically away from the target instead. We found that the two-stage competition is crucial for reproducing the complex behavior and neuronal activity observed in the antisaccade task across multiple brain regions. Notably, our model demonstrates two types of errors: fast and slow. Fast errors result from failing to inhibit the quick automatic responses and therefore exhibit very short response times. Slow errors, in contrast, are due to incorrect decisions in the remapping process and exhibit long response times comparable to those of correct antisaccade responses. The model thus reveals a circuit mechanism for the empirically observed slow errors and broad distributions of erroneous response times in antisaccade. Our work suggests that selecting between competing automatic and voluntary actions in behavioral control can be understood in terms of near-threshold decision-making, sharing a common recurrent (attractor) neural circuit mechanism with discrimination in perception.

Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

PubMed

VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

2016-01-01

People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

Neuroprotection in Hypoxic-Ischemic Brain Injury Targeting Glial Cells.

PubMed

Mucci, Sofia; Herrera, Maria Ines; Barreto, George E; Kolliker-Frers, Rodolfo; Capani, Francisco

2017-01-01

Brain injury constitutes a disabling health condition of several etiologies. One of the major causes of brain injury is hypoxia-ischemia. Until recently, pharmacological treatments were solely focused on neurons. In the last decades, glial cells started to be considered as alternative targets for neuroprotection. Novel treatments for hypoxia-ischemia intend to modulate reactive forms of glial cells, and/or potentiate their recovery response. In this review, we summarize these neuroprotective strategies in hypoxia-ischemia and discuss their mechanisms of action. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

PubMed

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

2014-11-01

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

Transient activation of dopaminergic neurons during development modulates visual responsiveness, locomotion and brain activity in a dopamine ontogeny model of schizophrenia.

PubMed

Calcagno, B; Eyles, D; van Alphen, B; van Swinderen, B

2013-01-08

It has been observed that certain developmental environmental risk factors for schizophrenia when modeled in rodents alter the trajectory of dopaminergic development, leading to persistent behavioural changes in adults. This has recently been articulated as the "dopamine ontogeny hypothesis of schizophrenia". To test one aspect of this hypothesis, namely that transient dopaminergic effects during development modulate attention-like behavior and arousal in adults, we turned to a small-brain model, Drosophila melanogaster. By applying genetic tools allowing transient activation or silencing of dopaminergic neurons in the fly brain, we investigated whether a critical window exists during development when altered dopamine (DA) activity levels could lead to impairments in arousal states in adult animals. We found that increased activity in dopaminergic neurons in later stages of development significantly increased visual responsiveness and locomotion, especially in adult males. This misallocation of visual salience and hyperactivity mimicked the effect of acute methamphetamine feeding to adult flies, suggesting up-regulated DA signaling could result from developmental manipulations. Finally, brain recordings revealed significantly reduced gamma-band activity in adult animals exposed to the transient developmental insult. Together, these data support the idea that transient alterations in DA signaling during development can permanently alter behavior in adults, and that a reductionist model such as Drosophila can be used to investigate potential mechanisms underlying complex cognitive disorders such as schizophrenia.

Deliberate or unintended: Intentions modulate empathic responses to others' economic payoffs in social interactions.

PubMed

Ma, Qingguo; Meng, Liang; Shen, Qiang

2017-12-01

Previous studies examining empathy have revealed the neural substrates of how the physical pain of others is represented in the human brain. However, little is known about the empathic modulation of behavioral and neural responses to others' economic payoffs, especially in the social context. In the present study, we engaged participants in a revised Dictator Game as observers who observe the powerless players receiving varied offers proposed by the dominant players, establishing the link between empathy and fairness perception. Results showed that unfair division schemes elicited a more pronounced FRN than fair ones only if a human agent proposed the initial offer. In addition, observers sacrificed their own payments to adjust unfair proposals, especially when a human agent proposed the offer. Thus, results of the current study demonstrated that perceived intention modulates behavioral and neural responses to others' economic payoffs in social interactions.

Populations of striatal medium spiny neurons encode vibrotactile frequency in rats: modulation by slow wave oscillations

PubMed Central

Hawking, Thomas G.

2013-01-01

Dorsolateral striatum (DLS) is implicated in tactile perception and receives strong projections from somatosensory cortex. However, the sensory representations encoded by striatal projection neurons are not well understood. Here we characterized the contribution of DLS to the encoding of vibrotactile information in rats by assessing striatal responses to precise frequency stimuli delivered to a single vibrissa. We applied stimuli in a frequency range (45–90 Hz) that evokes discriminable percepts and carries most of the power of vibrissa vibration elicited by a range of complex fine textures. Both medium spiny neurons and evoked potentials showed tactile responses that were modulated by slow wave oscillations. Furthermore, medium spiny neuron population responses represented stimulus frequency on par with previously reported behavioral benchmarks. Our results suggest that striatum encodes frequency information of vibrotactile stimuli which is dynamically modulated by ongoing brain state. PMID:23114217

Alpha Power Modulates Perception Independently of Endogenous Factors.

PubMed

Brüers, Sasskia; VanRullen, Rufin

2018-01-01

Oscillations are ubiquitous in the brain. Alpha oscillations in particular have been proposed to play an important role in sensory perception. Past studies have shown that the power of ongoing EEG oscillations in the alpha band is negatively correlated with visual outcome. Moreover, it also co-varies with other endogenous factors such as attention, vigilance, or alertness. In turn, these endogenous factors influence visual perception. Therefore, it remains unclear how much of the relation between alpha and perception is indirectly mediated by such endogenous factors, and how much reflects a direct causal influence of alpha rhythms on sensory neural processing. We propose to disentangle the direct from the indirect causal routes by introducing modulations of alpha power, independently of any fluctuations in endogenous factors. To this end, we use white-noise sequences to constrain the brain activity of 20 participants. The cross-correlation between the white-noise sequences and the concurrently recorded EEG reveals the impulse response function (IRF), a model of the systematic relationship between stimulation and brain response. These IRFs are then used to reconstruct rather than record the brain activity linked with new random sequences (by convolution). Interestingly, this reconstructed EEG only contains information about oscillations directly linked to the white-noise stimulation; fluctuations in attention and other endogenous factors may still modulate brain alpha rhythms during the task, but our reconstructed EEG is immune to these factors. We found that the detection of near-perceptual threshold targets embedded within these new white-noise sequences depended on the power of the ~10 Hz reconstructed EEG over parieto-occipital channels. Around the time of presentation, higher power led to poorer performance. Thus, fluctuations in alpha power, induced here by random luminance sequences, can directly influence perception: the relation between alpha power and perception is not a mere consequence of fluctuations in endogenous factors.

Somatostatin-28 modulates prepulse inhibition of the acoustic startle response, reward processes and spontaneous locomotor activity in rats

PubMed Central

Semenova, Svetlana; Hoyer, Daniel; Geyer, Mark A.; Markou, Athina

2011-01-01

Somatostatins have been shown to be involved in the pathophysiology of motor and affective disorders, as well as psychiatry disorders, including schizophrenia. We hypothesized that in addition to motor function, somatostatin may be involved in somatosensory gating and reward processes that have been shown to be dysregulated in schizophrenia. Accordingly, we evaluated the effects of intracerebroventricular administration of somatostatin-28 on spontaneous locomotor and exploratory behavior measured in a behavioral pattern monitor, sensorimotor gating, prepulse inhibition (PPI) of the acoustic startle reflex, and brain reward function (measured in a discrete trial intracranial self-stimulation procedure) in rats. Somatostatin-28 decreased spontaneous locomotor activity during the first 10 min of a 60 min testing session with no apparent changes in the exploratory activity of rats. The highest somatostatin-28 dose (10 μg/5 μl/side) induced PPI deficits with no effect on the acoustic startle response or startle response habituation. The somatostatin-induced PPI deficit was partially reversed by administration of SRA-880, a selective somatostatin 1 (sst1) receptor antagonist. Somatostatin-28 also induced elevations in brain reward thresholds, reflecting an anhedonic-like state. SRA-880 had no effect on brain reward function under baseline conditions. Altogether these findings suggest that somatostatin-28 modulates PPI and brain reward function but does not have a robust effect on spontaneous exploratory activity. Thus, increases in somatostatin transmission may represent one of the neurochemical mechanisms underlying anhedonia, one of the negative symptoms of schizophrenia, and sensorimotor gating deficits associated with cognitive impairments in schizophrenia patients. PMID:20537385

Emotion regulation modulates anticipatory brain activity that predicts emotional memory encoding in women.

PubMed

Galli, Giulia; Griffiths, Victoria A; Otten, Leun J

2014-03-01

It has been shown that the effectiveness with which unpleasant events are encoded into memory is related to brain activity set in train before the events. Here, we assessed whether encoding-related activity before an aversive event can be modulated by emotion regulation. Electrical brain activity was recorded from the scalps of healthy women while they performed an incidental encoding task on randomly intermixed unpleasant and neutral visual scenes. A cue presented 1.5 s before each picture indicated the upcoming valence. In half of the blocks of trials, the instructions emphasized to let emotions arise in a natural way. In the other half, participants were asked to decrease their emotional response by adopting the perspective of a detached observer. Memory for the scenes was probed 1 day later with a recognition memory test. Brain activity before unpleasant scenes predicted later memory of the scenes, but only when participants felt their emotions and did not detach from them. The findings indicate that emotion regulation can eliminate the influence of anticipatory brain activity on memory encoding. This may be relevant for the understanding and treatment of psychiatric diseases with a memory component.

An imaging genetics approach to understanding social influence

PubMed Central

Falk, Emily B.; Way, Baldwin M.; Jasinska, Agnes J.

2012-01-01

Normative social influences shape nearly every aspect of our lives, yet the biological processes mediating the impact of these social influences on behavior remain incompletely understood. In this Hypothesis, we outline a theoretical framework and an integrative research approach to the study of social influences on the brain and genetic moderators of such effects. First, we review neuroimaging evidence linking social influence and conformity to the brain's reward system. We next review neuroimaging evidence linking social punishment (exclusion) to brain systems involved in the experience of pain, as well as evidence linking exclusion to conformity. We suggest that genetic variants that increase sensitivity to social cues may predispose individuals to be more sensitive to either social rewards or punishments (or potentially both), which in turn increases conformity and susceptibility to normative social influences more broadly. To this end, we review evidence for genetic moderators of neurochemical responses in the brain, and suggest ways in which genes and pharmacology may modulate sensitivity to social influences. We conclude by proposing an integrative imaging genetics approach to the study of brain mediators and genetic modulators of a variety of social influences on human attitudes, beliefs, and actions. PMID:22701416

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

PubMed

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

2010-01-01

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

Central angiotensin modulation of baroreflex control of renal sympathetic nerve activity in the rat: influence of dietary sodium.

PubMed

DiBona, G F

2003-03-01

Administration of angiotensin II (angII) into the cerebral ventricles or specific brain sites impairs arterial baroreflex regulation of renal sympathetic nerve activity (SNA). Further insight into this effect was derived from: (a) using specific non-peptide angII receptor antagonists to assess the role of endogenous angII acting on angII receptor subtypes, (b) microinjection of angII receptor antagonists into brain sites behind an intact blood-brain barrier to assess the role of endogenous angII of brain origin and (c) alterations in dietary sodium intake, a known physiological regulator of activity of the renin-angiotensin system (RAS), to assess the ability to physiologically regulate the activity of the brain RAS. In rats in balance on low, normal or dietary sodium intake, losartan or candesartan was injected into the lateral cerebral ventricle or the rostral ventrolateral medulla (RVLM) and the effects on basal renal SNA and the arterial baroreflex sigmoidal relationship between renal SNA and arterial pressure were determined. With both routes of administration, the effects were proportional to the activity of the RAS as indexed by plasma renin activity (PRA). The magnitude of both the decrease in basal renal SNA and the parallel resetting of arterial baroreflex regulation of renal SNA to a lower arterial pressure was greatest in low-sodium rats with highest PRA and least in high-sodium rats with lowest PRA. Disinhibition of the paraventricular nucleus (PVN) by injection of bicuculline causes pressor, tachycardic and renal sympathoexcitatory responses mediated via an angiotensinergic projection from PVN to RVLM. In comparison with responses in normal sodium rats, these responses were greatly diminished in high-sodium rats and greatly enhanced in low-sodium rats. Physiological changes in the activity of the RAS produced by alterations in dietary sodium intake regulate the contribution of endogenous angII of brain origin in the modulation of arterial baroreflex regulation of renal SNA.

Effects of Oxytocin and Vasopressin on Preferential Brain Responses to Negative Social Feedback.

PubMed

Gozzi, Marta; Dashow, Erica M; Thurm, Audrey; Swedo, Susan E; Zink, Caroline F

2017-06-01

Receiving negative social feedback can be detrimental to emotional, cognitive, and physical well-being, and fear of negative social feedback is a prominent feature of mental illnesses that involve social anxiety. A large body of evidence has implicated the neuropeptides oxytocin and vasopressin in the modulation of human neural activity underlying social cognition, including negative emotion processing; however, the influence of oxytocin and vasopressin on neural activity elicited during negative social evaluation remains unknown. Here 21 healthy men underwent functional magnetic resonance imaging in a double-blind, placebo-controlled, crossover design to determine how intranasally administered oxytocin and vasopressin modulated neural activity when receiving negative feedback on task performance from a study investigator. We found that under placebo, a preferential response to negative social feedback compared with positive social feedback was evoked in brain regions putatively involved in theory of mind (temporoparietal junction), pain processing (anterior insula and supplementary motor area), and identification of emotionally important visual cues in social perception (right fusiform). These activations weakened with oxytocin and vasopressin administration such that neural responses to receiving negative social feedback were not significantly greater than positive social feedback. Our results show effects of both oxytocin and vasopressin on the brain network involved in negative social feedback, informing the possible use of a pharmacological approach targeting these regions in multiple disorders with impairments in social information processing.

Competition in the Brain. The Contribution of EEG and fNIRS Modulation and Personality Effects in Social Ranking.

PubMed

Balconi, Michela; Vanutelli, Maria E

2016-01-01

In the present study, the social ranking perception in competition was explored. Brain response (alpha band oscillations, EEG; hemodynamic activity, O2Hb), as well as self-perception of social ranking, cognitive performance, and personality trait (Behavioral Activation System, BAS) were considered during a competitive joint-action. Subjects were required to develop a strategy to obtain a better outcome than a competitor (C) (in term of error rate, and response time, RT). A pre-feedback (without a specific feedback on the performance) and a post-feedback condition (which reinforced the improved performance) were provided. It was found that higher-BAS participants responded in greater measure to perceived higher cognitive performance (post-feedback condition), with increased left prefrontal activity, higher ranking perception, and a better real performance (reduced RTs). These results were explained in term of increased sense of self-efficacy and social position, probably based on higher-BAS sensitivity to reinforcing conditions. In addition, the hemispheric effect in favor of the left side characterized the competitive behavior, showing an imbalance for high-BAS in comparison to low-BAS in the case of a rewarding (post-feedback) context. Therefore, the present results confirmed the significance of BAS in modulating brain responsiveness, self-perceived social position, and real performance during an interpersonal competitive action which is considered highly relevant for social status.

Is a Responsive Default Mode Network Required for Successful Working Memory Task Performance?

PubMed Central

Čeko, Marta; Gracely, John L.; Fitzcharles, Mary-Ann; Seminowicz, David A.; Schweinhardt, Petra

2015-01-01

In studies of cognitive processing using tasks with externally directed attention, regions showing increased (external-task-positive) and decreased or “negative” [default-mode network (DMN)] fMRI responses during task performance are dynamically responsive to increasing task difficulty. Responsiveness (modulation of fMRI signal by increasing load) has been linked directly to successful cognitive task performance in external-task-positive regions but not in DMN regions. To investigate whether a responsive DMN is required for successful cognitive performance, we compared healthy human subjects (n = 23) with individuals shown to have decreased DMN engagement (chronic pain patients, n = 28). Subjects performed a multilevel working-memory task (N-back) during fMRI. If a responsive DMN is required for successful performance, patients having reduced DMN responsiveness should show worsened performance; if performance is not reduced, their brains should show compensatory activation in external-task-positive regions or elsewhere. All subjects showed decreased accuracy and increased reaction times with increasing task level, with no significant group differences on either measure at any level. Patients had significantly reduced negative fMRI response (deactivation) of DMN regions (posterior cingulate/precuneus, medial prefrontal cortex). Controls showed expected modulation of DMN deactivation with increasing task difficulty. Patients showed significantly reduced modulation of DMN deactivation by task difficulty, despite their successful task performance. We found no evidence of compensatory neural recruitment in external-task-positive regions or elsewhere. Individual responsiveness of the external-task-positive ventrolateral prefrontal cortex, but not of DMN regions, correlated with task accuracy. These findings suggest that a responsive DMN may not be required for successful cognitive performance; a responsive external-task-positive network may be sufficient. SIGNIFICANCE STATEMENT We studied the relationship between responsiveness of the brain to increasing task demand and successful cognitive performance, using chronic pain patients as a probe. fMRI working memory studies show that two main cognitive networks [“external-task positive” and “default-mode network” (DMN)] are responsive to increasing task difficulty. The responsiveness of both of these brain networks is suggested to be required for successful task performance. The responsiveness of external-task-positive regions has been linked directly to successful cognitive task performance, as we also show here. However, pain patients show decreased engagement and responsiveness of the DMN but can perform a working memory task as well as healthy subjects, without demonstrable compensatory neural recruitment. Therefore, a responsive DMN might not be needed for successful cognitive performance. PMID:26290236

Is a Responsive Default Mode Network Required for Successful Working Memory Task Performance?

PubMed

Čeko, Marta; Gracely, John L; Fitzcharles, Mary-Ann; Seminowicz, David A; Schweinhardt, Petra; Bushnell, M Catherine

2015-08-19

In studies of cognitive processing using tasks with externally directed attention, regions showing increased (external-task-positive) and decreased or "negative" [default-mode network (DMN)] fMRI responses during task performance are dynamically responsive to increasing task difficulty. Responsiveness (modulation of fMRI signal by increasing load) has been linked directly to successful cognitive task performance in external-task-positive regions but not in DMN regions. To investigate whether a responsive DMN is required for successful cognitive performance, we compared healthy human subjects (n = 23) with individuals shown to have decreased DMN engagement (chronic pain patients, n = 28). Subjects performed a multilevel working-memory task (N-back) during fMRI. If a responsive DMN is required for successful performance, patients having reduced DMN responsiveness should show worsened performance; if performance is not reduced, their brains should show compensatory activation in external-task-positive regions or elsewhere. All subjects showed decreased accuracy and increased reaction times with increasing task level, with no significant group differences on either measure at any level. Patients had significantly reduced negative fMRI response (deactivation) of DMN regions (posterior cingulate/precuneus, medial prefrontal cortex). Controls showed expected modulation of DMN deactivation with increasing task difficulty. Patients showed significantly reduced modulation of DMN deactivation by task difficulty, despite their successful task performance. We found no evidence of compensatory neural recruitment in external-task-positive regions or elsewhere. Individual responsiveness of the external-task-positive ventrolateral prefrontal cortex, but not of DMN regions, correlated with task accuracy. These findings suggest that a responsive DMN may not be required for successful cognitive performance; a responsive external-task-positive network may be sufficient. We studied the relationship between responsiveness of the brain to increasing task demand and successful cognitive performance, using chronic pain patients as a probe. fMRI working memory studies show that two main cognitive networks ["external-task positive" and "default-mode network" (DMN)] are responsive to increasing task difficulty. The responsiveness of both of these brain networks is suggested to be required for successful task performance. The responsiveness of external-task-positive regions has been linked directly to successful cognitive task performance, as we also show here. However, pain patients show decreased engagement and responsiveness of the DMN but can perform a working memory task as well as healthy subjects, without demonstrable compensatory neural recruitment. Therefore, a responsive DMN might not be needed for successful cognitive performance. Copyright © 2015 the authors 0270-6474/15/3511596-11$15.00/0.

Hepatic Expression of Serum Amyloid A1 Is Induced by Traumatic Brain Injury and Modulated by Telmisartan

PubMed Central

Villapol, Sonia; Kryndushkin, Dmitry; Balarezo, Maria G.; Campbell, Ashley M.; Saavedra, Juan M.; Shewmaker, Frank P.; Symes, Aviva J.

2016-01-01

Traumatic brain injury affects the whole body in addition to the direct impact on the brain. The systemic response to trauma is associated with the hepatic acute-phase response. To further characterize this response, we performed controlled cortical impact injury on male mice and determined the expression of serum amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute-phase response in liver and plasma. After cortical impact injury, induction of SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post-injury, followed by gradual diminution over time. In the liver, cortical impact injury increased neutrophil and macrophage infiltration, apoptosis, and expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed. Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not affect CXCL1 expression or the number of apoptotic cells or infiltrating leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is induced in the liver after traumatic brain injury and that telmisartan prevents this response. Elucidating the molecular pathogenesis of the liver after brain injury will assist in understanding the efficacy of therapeutic approaches to brain injury. PMID:26435412

Sex differences in memory of emotional images: a behavioral and electrophysiological investigation.

PubMed

Glaser, Emma; Mendrek, Adrianna; Germain, Martine; Lakis, Nadia; Lavoie, Marc E

2012-07-01

Current research suggests that emotional responses differ between men and women. Sex differences regarding emotional effects on memory have been recently studied through brain imaging techniques. However, the majority of investigations have often neglected to balance the variable of emotional intensity (arousal) across pleasant and unpleasant pictures. Additionally, men and women were often mixed or studied separately. The current study aims at comparing men and women's electrophysiological responses related to emotional memory of photographic material. These responses were measured using Event Related brain Potentials (ERP) in response to a task of episodic memory of emotional images. The frontal N200, the parietal P300 and the central LPC were compared in 17 men and 17 women matched for age, social economic status, education and intelligence. Behavioral results showed that, in men, reaction times were modulated by valence, whereas for women, reaction times were mainly modulated by arousal. Accuracy was affected by both emotional valence and arousal, but only in women. ERP analyses revealed that emotional valence influenced earlier time components (frontal N200 and parietal P300), whereas arousal influenced memory in the later time component (central LPC). Moreover, sex differences, mediated by valence and arousal, were found in ERP responses at different times in the processing stream. Copyright © 2012 Elsevier B.V. All rights reserved.

The motilin agonist erythromycin increases hunger by modulating homeostatic and hedonic brain circuits in healthy women: a randomized, placebo-controlled study.

PubMed

Zhao, Dongxing; Meyer-Gerspach, Anne Christin; Deloose, Eveline; Iven, Julie; Weltens, Nathalie; Depoortere, Inge; O'daly, Owen; Tack, Jan; Van Oudenhove, Lukas

2018-01-29

The motilin agonist, erythromycin, induces gastric phase III of the migrating motor complex, which in turn generates hunger peaks. To identify the brain mechanisms underlying these orexigenic effects, 14 healthy women participated in a randomized, placebo-controlled crossover study. Functional magnetic resonance brain images were acquired for 50 minutes interprandially. Intravenous infusion of erythromycin (40 mg) or saline started 10 minutes after the start of scanning. Blood samples (for glucose and hormone levels) and hunger ratings were collected at fixed timepoints. Thirteen volunteers completed the study, without any adverse events. Brain regions involved in homeostatic and hedonic control of appetite and food intake responded to erythromycin, including pregenual anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, amygdala, caudate, pallidum and putamen bilaterally, right accumbens, hypothalamus, and midbrain. Octanoylated ghrelin levels decreased, whereas both glucose and insulin increased after erythromycin. Hunger were higher after erythromycin, and these differences covaried with the brain response in most of the abovementioned regions. The motilin agonist erythromycin increases hunger by modulating neurocircuitry related to homeostatic and hedonic control of appetite and feeding. These results confirm recent behavioural findings identifying motilin as a key orexigenic hormone in humans, and identify the brain mechanisms underlying its effect.

Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro.

PubMed

Chaitanya, Ganta V; Cromer, Walter E; Wells, Shannon R; Jennings, Merilyn H; Couraud, P Olivier; Romero, Ignacio A; Weksler, Babette; Erdreich-Epstein, Anat; Mathis, J Michael; Minagar, Alireza; Alexander, J Steven

2011-11-23

The glio-vascular unit (G-unit) plays a prominent role in maintaining homeostasis of the blood-brain barrier (BBB) and disturbances in cells forming this unit may seriously dysregulate BBB. The direct and indirect effects of cytokines on cellular components of the BBB are not yet unclear. The present study compares the effects of cytokines and cytokine-treated astrocytes on brain endothelial barrier. 3-dimensional transwell co-cultures of brain endothelium and related-barrier forming cells with astrocytes were used to investigate gliovascular barrier responses to cytokines during pathological stresses. Gliovascular barrier was measured using trans-endothelial electrical resistance (TEER), a sensitive index of in vitro barrier integrity. We found that neither TNF-α, IL-1β or IFN-γ directly reduced barrier in human or mouse brain endothelial cells or ECV-304 barrier (independent of cell viability/metabolism), but found that astrocyte exposure to cytokines in co-culture significantly reduced endothelial (and ECV-304) barrier. These results indicate that the barrier established by human and mouse brain endothelial cells (and other cells) may respond positively to cytokines alone, but that during pathological conditions, cytokines dysregulate the barrier forming cells indirectly through astrocyte activation involving reorganization of junctions, matrix, focal adhesion or release of barrier modulating factors (e.g. oxidants, MMPs). © 2011 Chaitanya et al; licensee BioMed Central Ltd.

Effects of emotional valence and three-dimensionality of visual stimuli on brain activation: an fMRI study.

PubMed

Dores, A R; Almeida, I; Barbosa, F; Castelo-Branco, M; Monteiro, L; Reis, M; de Sousa, L; Caldas, A Castro

2013-01-01

Examining changes in brain activation linked with emotion-inducing stimuli is essential to the study of emotions. Due to the ecological potential of techniques such as virtual reality (VR), inspection of whether brain activation in response to emotional stimuli can be modulated by the three-dimensional (3D) properties of the images is important. The current study sought to test whether the activation of brain areas involved in the emotional processing of scenarios of different valences can be modulated by 3D. Therefore, the focus was made on the interaction effect between emotion-inducing stimuli of different emotional valences (pleasant, unpleasant and neutral valences) and visualization types (2D, 3D). However, main effects were also analyzed. The effect of emotional valence and visualization types and their interaction were analyzed through a 3 × 2 repeated measures ANOVA. Post-hoc t-tests were performed under a ROI-analysis approach. The results show increased brain activation for the 3D affective-inducing stimuli in comparison with the same stimuli in 2D scenarios, mostly in cortical and subcortical regions that are related to emotional processing, in addition to visual processing regions. This study has the potential of clarify brain mechanisms involved in the processing of emotional stimuli (scenarios' valence) and their interaction with three-dimensionality.

Clarifying the Ghrelin System's Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand.

PubMed

Edwards, Alexander; Abizaid, Alfonso

2017-04-19

Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor (GHSR), a receptor found in relatively high concentrations in hypothalamic and mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can be explained by the effects of this hormone on regions of the brain that have a more permeable blood brain barrier (BBB), ghrelin produced within the periphery demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are expressed. Therefore, one of the most pressing unanswered questions plaguing ghrelin research is how GHSRs, distributed in brain regions protected by the BBB, are activated despite ghrelin's predominant peripheral production and poor ability to transverse the BBB. This manuscript will describe how peripheral ghrelin activates central GHSRs to encourage feeding, and how central ghrelin synthesis and ghrelin independent activation of GHSRs may also contribute to the modulation of feeding behaviours.

The Nervous System and Gastrointestinal Function

ERIC Educational Resources Information Center

Altaf, Muhammad A.; Sood, Manu R.

2008-01-01

The enteric nervous system is an integrative brain with collection of neurons in the gastrointestinal tract which is capable of functioning independently of the central nervous system (CNS). The enteric nervous system modulates motility, secretions, microcirculation, immune and inflammatory responses of the gastrointestinal tract. Dysphagia,…

Functional imaging of the human brain using a modular, fibre-less, high-density diffuse optical tomography system.

PubMed

Chitnis, Danial; Cooper, Robert J; Dempsey, Laura; Powell, Samuel; Quaggia, Simone; Highton, David; Elwell, Clare; Hebden, Jeremy C; Everdell, Nicholas L

2016-10-01

We present the first three-dimensional, functional images of the human brain to be obtained using a fibre-less, high-density diffuse optical tomography system. Our technology consists of independent, miniaturized, silicone-encapsulated DOT modules that can be placed directly on the scalp. Four of these modules were arranged to provide up to 128, dual-wavelength measurement channels over a scalp area of approximately 60 × 65 mm 2 . Using a series of motor-cortex stimulation experiments, we demonstrate that this system can obtain high-quality, continuous-wave measurements at source-detector separations ranging from 14 to 55 mm in adults, in the presence of hair. We identify robust haemodynamic response functions in 5 out of 5 subjects, and present diffuse optical tomography images that depict functional haemodynamic responses that are well-localized in all three dimensions at both the individual and group levels. This prototype modular system paves the way for a new generation of wearable, wireless, high-density optical neuroimaging technologies.

In the eye of the beholder: individual differences in reward-drive modulate early frontocentral ERPs to angry faces.

PubMed

Bediou, Benoit; Eimer, Martin; d'Amato, Thierry; Hauk, Olaf; Calder, Andrew J

2009-02-01

Individual differences in reward-drive have been associated with increased attention toward facial signals of aggression, heightened experience of anger and vulnerability to display aggressive behaviour. Recent fMRI research suggests that these effects rely on reduced ventromedial prefrontal (and increased amygdala) response to aggressive facial displays compared with neutral and sad expressions in subjects scoring high on reward-drive. However, nothing is known about the timing of this modulation. Using event-related potentials (ERPs), we provide the first evidence that greater proneness to display hostile and aggressive behaviour (measured by high scores on the reward-drive) is associated with a reduced midline frontocentral response to aggressive faces within 200-300ms. In addition to confirming a particular interaction between anger processing and aggression related personality traits in ventromedial prefrontal brain regions, our study brings a first indication of when their interaction occurs in the brain, strengthening results from previous classical as well as functional connectivity fMRI studies.

Response properties of nucleus reticularis lateralis neurons after electroacupuncture stimulation in rats.

PubMed

Moritaka, Kentaro; Zeredo, Jorge L; Kimoto, Mari; Nasution, Fajar H; Hirano, Takafumi; Toda, Kazuo

2010-01-01

A descending inhibitory mechanism from the periaqueductal gray (PAG) to the spinal cord through the nucleus raphe magnus (NRM) is strongly involved in endogenous analgesic system produced by acupuncture stimulation. In addition to the PAG to NRM system which descends in the medial pathway of the brain stem, the nucleus reticularis lateralis (NRL) situated in the lateral part of the brain stem is reported to play an important role in modulating centrifugal antinociceptive action. In the present study, to clarify the role of NRL in acupuncture analgesia, we investigated the response properties of NRL neurons to acupuncture stimulation. The majority of NRM-projecting NRL neurons were inhibited by electroacupuncture stimulation. This effect was antagonized by ionophoretic application of naloxone, indicating that endogenous opioids act directly onto these NRL neurons. By contrast, about half of spinal projecting NRL neurons were excited by electroacupuncture stimulation, suggesting that part of the NRL neurons may modulate pain transmission directly at the spinal level.

Axonal Conduction Delays, Brain State, and Corticogeniculate Communication.

PubMed

Stoelzel, Carl R; Bereshpolova, Yulia; Alonso, Jose-Manuel; Swadlow, Harvey A

2017-06-28

Thalamocortical conduction times are short, but layer 6 corticothalamic axons display an enormous range of conduction times, some exceeding 40-50 ms. Here, we investigate (1) how axonal conduction times of corticogeniculate (CG) neurons are related to the visual information conveyed to the thalamus, and (2) how alert versus nonalert awake brain states affect visual processing across the spectrum of CG conduction times. In awake female Dutch-Belted rabbits, we found 58% of CG neurons to be visually responsive, and 42% to be unresponsive. All responsive CG neurons had simple, orientation-selective receptive fields, and generated sustained responses to stationary stimuli. CG axonal conduction times were strongly related to modulated firing rates (F1 values) generated by drifting grating stimuli, and their associated interspike interval distributions, suggesting a continuum of visual responsiveness spanning the spectrum of axonal conduction times. CG conduction times were also significantly related to visual response latency, contrast sensitivity (C-50 values), directional selectivity, and optimal stimulus velocity. Increasing alertness did not cause visually unresponsive CG neurons to become responsive and did not change the response linearity (F1/F0 ratios) of visually responsive CG neurons. However, for visually responsive CG neurons, increased alertness nearly doubled the modulated response amplitude to optimal visual stimulation (F1 values), significantly shortened response latency, and dramatically increased response reliability. These effects of alertness were uniform across the broad spectrum of CG axonal conduction times. SIGNIFICANCE STATEMENT Corticothalamic neurons of layer 6 send a dense feedback projection to thalamic nuclei that provide input to sensory neocortex. While sensory information reaches the cortex after brief thalamocortical axonal delays, corticothalamic axons can exhibit conduction delays of <2 ms to 40-50 ms. Here, in the corticogeniculate visual system of awake rabbits, we investigate the functional significance of this axonal diversity, and the effects of shifting alert/nonalert brain states on corticogeniculate processing. We show that axonal conduction times are strongly related to multiple visual response properties, suggesting a continuum of visual responsiveness spanning the spectrum of corticogeniculate axonal conduction times. We also show that transitions between awake brain states powerfully affect corticogeniculate processing, in some ways more strongly than in layer 4. Copyright © 2017 the authors 0270-6474/17/376342-17$15.00/0.

Intranasal oxytocin modulates neural functional connectivity during human social interaction.

PubMed

Rilling, James K; Chen, Xiangchuan; Chen, Xu; Haroon, Ebrahim

2018-02-10

Oxytocin (OT) modulates social behavior in primates and many other vertebrate species. Studies in non-primate animals have demonstrated that, in addition to influencing activity within individual brain areas, OT influences functional connectivity across networks of areas involved in social behavior. Previously, we used fMRI to image brain function in human subjects during a dyadic social interaction task following administration of either intranasal oxytocin (INOT) or placebo, and analyzed the data with a standard general linear model. Here, we conduct an extensive re-analysis of these data to explore how OT modulates functional connectivity across a neural network that animal studies implicate in social behavior. OT induced widespread increases in functional connectivity in response to positive social interactions among men and widespread decreases in functional connectivity in response to negative social interactions among women. Nucleus basalis of Meynert, an important regulator of selective attention and motivation with a particularly high density of OT receptors, had the largest number of OT-modulated connections. Regions known to receive mesolimbic dopamine projections such as the nucleus accumbens and lateral septum were also hubs for OT effects on functional connectivity. Our results suggest that the neural mechanism by which OT influences primate social cognition may include changes in patterns of activity across neural networks that regulate social behavior in other animals. © 2018 Wiley Periodicals, Inc.

Aberrant reward center response to partner reputation during a social exchange game in generalized social phobia.

PubMed

Sripada, Chandra; Angstadt, Michael; Liberzon, Israel; McCabe, Kevin; Phan, K Luan

2013-04-01

Generalized social anxiety disorder (GSAD) is characterized by excessive fear of public scrutiny and reticence in social engagement. Previous studies have probed the neural basis of GSAD often using static, noninteractive stimuli (e.g., face photographs) and have identified dysfunction in fear circuitry. We sought to investigate brain-based dysfunction in GSAD during more real-world, dynamic social interactions, focusing on the role of reward-related regions that are implicated in social decision-making. Thirty-six healthy individuals (healthy control [HC]) and 36 individuals with GSAD underwent functional magnetic resonance imaging (fMRI) scanning while participating in a behavioral economic game ("Trust Game") involving iterative exchanges with fictive partners who acquire differential reputations for reciprocity. We investigated brain responses to reciprocation of trust in one's social partner, and how these brain responses are modulated by partner reputation for repayment. In both HC and GSAD, receipt of reciprocity robustly engaged ventral striatum, a region implicated in reward. In HC, striatal responses to reciprocity were specific to partners who have consistently returned the investment ("cooperative partners"), and were absent for partners who lack a cooperative reputation. In GSAD, modulation of striatal responses by partner reputation was absent. Social anxiety severity predicted diminished responses to cooperative partners. These results suggest abnormalities in GSAD in reward-related striatal mechanisms that may be important for the initiation, valuation, and maintenance of cooperative social relationships. Moreover, this study demonstrates that dynamic, interactive task paradigms derived from economics can help illuminate novel mechanisms of pathology in psychiatric illnesses in which social dysfunction is a cardinal feature. © 2013 Wiley Periodicals, Inc.

Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice.

PubMed

MacPherson, Kathryn P; Sompol, Pradoldej; Kannarkat, George T; Chang, Jianjun; Sniffen, Lindsey; Wildner, Mary E; Norris, Christopher M; Tansey, Malú G

2017-06-01

Clinical and animal model studies have implicated inflammation and peripheral immune cell responses in the pathophysiology of Alzheimer's disease (AD). Peripheral immune cells including T cells circulate in the cerebrospinal fluid (CSF) of healthy adults and are found in the brains of AD patients and AD rodent models. Blocking entry of peripheral macrophages into the CNS was reported to increase amyloid burden in an AD mouse model. To assess inflammation in the 5xFAD (Tg) mouse model, we first quantified central and immune cell profiles in the deep cervical lymph nodes and spleen. In the brains of Tg mice, activated (MHCII + , CD45 high , and Ly6C high ) myeloid-derived CD11b + immune cells are decreased while CD3 + T cells are increased as a function of age relative to non-Tg mice. These immunological changes along with evidence of increased mRNA levels for several cytokines suggest that immune regulation and trafficking patterns are altered in Tg mice. Levels of soluble Tumor Necrosis Factor (sTNF) modulate blood-brain barrier (BBB) permeability and are increased in CSF and brain parenchyma post-mortem in AD subjects and Tg mice. We report here that in vivo peripheral administration of XPro1595, a novel biologic that sequesters sTNF into inactive heterotrimers, reduced the age-dependent increase in activated immune cells in Tg mice, while decreasing the overall number of CD4 + T cells. In addition, XPro1595 treatment in vivo rescued impaired long-term potentiation (LTP) measured in brain slices in association with decreased Aβ plaques in the subiculum. Selective targeting of sTNF may modulate brain immune cell infiltration, and prevent or delay neuronal dysfunction in AD. Immune cells and cytokines perform specialized functions inside and outside the brain to maintain optimal brain health; but the extent to which their activities change in response to neuronal dysfunction and degeneration is not well understood. Our findings indicate that neutralization of sTNF reduced the age-dependent increase in activated immune cells in Tg mice, while decreasing the overall number of CD4 + T cells. In addition, impaired long-term potentiation (LTP) was rescued by XPro1595 in association with decreased hippocampal Aβ plaques. Selective targeting of sTNF holds translational potential to modulate brain immune cell infiltration, dampen neuroinflammation, and prevent or delay neuronal dysfunction in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Alexithymia is associated with attenuated automatic brain response to facial emotion in clinical depression.

PubMed

Suslow, Thomas; Kugel, Harald; Rufer, Michael; Redlich, Ronny; Dohm, Katharina; Grotegerd, Dominik; Zaremba, Dario; Dannlowski, Udo

2016-02-04

Alexithymia is a clinically relevant personality trait related to difficulties in recognizing and describing emotions. Previous studies examining the neural correlates of alexithymia have shown mainly decreased response of several brain areas during emotion processing in healthy samples and patients suffering from autism or post-traumatic stress disorder. In the present study, we examined the effect of alexithymia on automatic brain reactivity to negative and positive facial expressions in clinical depression. Brain activation in response to sad, happy, neutral, and no facial expression (presented for 33 ms and masked by neutral faces) was measured by functional magnetic resonance imaging at 3 T in 26 alexithymic and 26 non-alexithymic patients with major depression. Alexithymic patients manifested less activation in response to masked sad and happy (compared to neutral) faces in right frontal regions and right caudate nuclei than non-alexithymic patients. Our neuroimaging study provides evidence that the personality trait alexithymia has a modulating effect on automatic emotion processing in clinical depression. Our findings support the idea that alexithymia could be associated with functional deficits of the right hemisphere. Future research on the neural substrates of emotion processing in depression should assess and control alexithymia in their analyses.

Prestimulus neural oscillations inhibit visual perception via modulation of response gain.

PubMed

Chaumon, Maximilien; Busch, Niko A

2014-11-01

The ongoing state of the brain radically affects how it processes sensory information. How does this ongoing brain activity interact with the processing of external stimuli? Spontaneous oscillations in the alpha range are thought to inhibit sensory processing, but little is known about the psychophysical mechanisms of this inhibition. We recorded ongoing brain activity with EEG while human observers performed a visual detection task with stimuli of different contrast intensities. To move beyond qualitative description, we formally compared psychometric functions obtained under different levels of ongoing alpha power and evaluated the inhibitory effect of ongoing alpha oscillations in terms of contrast or response gain models. This procedure opens the way to understanding the actual functional mechanisms by which ongoing brain activity affects visual performance. We found that strong prestimulus occipital alpha oscillations-but not more anterior mu oscillations-reduce performance most strongly for stimuli of the highest intensities tested. This inhibitory effect is best explained by a divisive reduction of response gain. Ongoing occipital alpha oscillations thus reflect changes in the visual system's input/output transformation that are independent of the sensory input to the system. They selectively scale the system's response, rather than change its sensitivity to sensory information.

Adolescents growing up amidst intractable conflict attenuate brain response to pain of outgroup

PubMed Central

Levy, Jonathan; Influs, Moran; Masalha, Shafiq; Zagoory-Sharon, Orna; Feldman, Ruth

2016-01-01

Adolescents’ participation in intergroup conflicts comprises an imminent global risk, and understanding its neural underpinnings may open new perspectives. We assessed Jewish-Israeli and Arab-Palestinian adolescents for brain response to the pain of ingroup/outgroup protagonists using magnetoencephalography (MEG), one-on-one positive and conflictual interactions with an outgroup member, attitudes toward the regional conflict, and oxytocin levels. A neural marker of ingroup bias emerged, expressed via alpha modulations in the somatosensory cortex (S1) that characterized an automatic response to the pain of all protagonists followed by rebound/enhancement to ingroup pain only. Adolescents’ hostile social interactions with outgroup members and uncompromising attitudes toward the conflict influenced this neural marker. Furthermore, higher oxytocin levels in the Jewish-Israeli majority and tighter brain-to-brain synchrony among group members in the Arab-Palestinian minority enhanced the neural ingroup bias. Findings suggest that in cases of intractable intergroup conflict, top-down control mechanisms may block the brain’s evolutionary-ancient resonance to outgroup pain, pinpointing adolescents’ interpersonal and sociocognitive processes as potential targets for intervention. PMID:27849588

Substance use modulates stress reactivity: Behavioral and physiological outcomes.

PubMed

Fosnocht, Anne Q; Briand, Lisa A

2016-11-01

Drug addiction is a major public health concern in the United States costing taxpayers billions in health care costs, lost productivity and law enforcement. However, the availability of effective treatment options remains limited. The development of novel therapeutics will not be possible without a better understanding of the addicted brain. Studies in both clinical and preclinical models indicate that chronic drug use leads to alterations in the body and brain's response to stress. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may shed light on the ability of stress to increase vulnerability to relapse. Further, within both the HPA axis and limbic brain regions, corticotropin-releasing factor (CRF) is critically involved in the brain's response to stress. Alterations in both central and peripheral CRF activity seen following chronic drug use provide a mechanism by which substance use can alter stress reactivity, thus mediating addictive phenotypes. While many reviews have focused on how stress alters drug-mediated changes in physiology and behavior, the goal of this review is to focus on how substance use alters responses to stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging.

PubMed

Phillips, Cristy

2017-01-01

The number of the elderly across the globe will approximate 2.1 billion by 2050. Juxtaposed against this burgeoning segment of the population is evidence that nonpathological aging is associated with an increased risk for cognitive decline in a variety of domains, changes that can cause mild disability even before the onset of dementia. Given that pharmacological treatments that mitigate dementia are still outstanding, alternative therapeutic options are being investigated increasingly. The results from translational studies have shown that modifiable lifestyle factors-including physical activity, cognitive engagement, and diet-are a key strategy for maintaining brain health during aging. Indeed, a multiplicity of studies has demonstrated relationships between lifestyle factors, brain structure and function, and cognitive function in aging adults. For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain whereas cognitive engagement enhances brain and cognitive reserve. The aims of this review are to evaluate the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging; to identify putative mechanisms that contribute positive brain aging; and to highlight future directions for scientists and clinicians. Undoubtedly, the translation of cutting-edge knowledge derived from the field of cognitive neuroscience will advance our understanding and enhance clinical treatment interventions as we endeavor to promote brain health during aging.

Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging

PubMed Central

2017-01-01

The number of the elderly across the globe will approximate 2.1 billion by 2050. Juxtaposed against this burgeoning segment of the population is evidence that nonpathological aging is associated with an increased risk for cognitive decline in a variety of domains, changes that can cause mild disability even before the onset of dementia. Given that pharmacological treatments that mitigate dementia are still outstanding, alternative therapeutic options are being investigated increasingly. The results from translational studies have shown that modifiable lifestyle factors—including physical activity, cognitive engagement, and diet—are a key strategy for maintaining brain health during aging. Indeed, a multiplicity of studies has demonstrated relationships between lifestyle factors, brain structure and function, and cognitive function in aging adults. For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain whereas cognitive engagement enhances brain and cognitive reserve. The aims of this review are to evaluate the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging; to identify putative mechanisms that contribute positive brain aging; and to highlight future directions for scientists and clinicians. Undoubtedly, the translation of cutting-edge knowledge derived from the field of cognitive neuroscience will advance our understanding and enhance clinical treatment interventions as we endeavor to promote brain health during aging. PMID:28695017

Influence of anodal transcranial direct current stimulation (tDCS) over the right angular gyrus on brain activity during rest.

PubMed

Clemens, Benjamin; Jung, Stefanie; Mingoia, Gianluca; Weyer, David; Domahs, Frank; Willmes, Klaus

2014-01-01

Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site.

Influence of Anodal Transcranial Direct Current Stimulation (tDCS) over the Right Angular Gyrus on Brain Activity during Rest

PubMed Central

Clemens, Benjamin; Jung, Stefanie; Mingoia, Gianluca; Weyer, David; Domahs, Frank; Willmes, Klaus

2014-01-01

Although numerous studies examined resting-state networks (RSN) in the human brain, so far little is known about how activity within RSN might be modulated by non-invasive brain stimulation applied over parietal cortex. Investigating changes in RSN in response to parietal cortex stimulation might tell us more about how non-invasive techniques such as transcranial direct current stimulation (tDCS) modulate intrinsic brain activity, and further elaborate our understanding of how the resting brain responds to external stimulation. Here we examined how activity within the canonical RSN changed in response to anodal tDCS applied over the right angular gyrus (AG). We hypothesized that changes in resting-state activity can be induced by a single tDCS session and detected with functional magnetic resonance imaging (fMRI). Significant differences between two fMRI sessions (pre-tDCS and post-tDCS) were found in several RSN, including the cerebellar, medial visual, sensorimotor, right frontoparietal, and executive control RSN as well as the default mode and the task positive network. The present results revealed decreased and increased RSN activity following tDCS. Decreased RSN activity following tDCS was found in bilateral primary and secondary visual areas, and in the right putamen. Increased RSN activity following tDCS was widely distributed across the brain, covering thalamic, frontal, parietal and occipital regions. From these exploratory results we conclude that a single session of anodal tDCS over the right AG is sufficient to induce large-scale changes in resting-state activity. These changes were localized in sensory and cognitive areas, covering regions close to and distant from the stimulation site. PMID:24760013

EFFECTS OF CONTINUOUS-WAVE, PULSED, AND SINUSOIDAL-AMPLITUDE-MODULATED MICROWAVES ON BRAIN ENERGY METABOLISM

EPA Science Inventory

A comparison of the effects of continuous wave, sinusoidal-amplitude modulated, and pulsed square-wave-modulated 591-MHz microwave exposures on brain energy metabolism was made in male Sprague Dawley rats (175-225g). Brain NADH fluorescence, adensine triphosphate (ATP) concentrat...

Redox modulation of cellular stress response and lipoxin A4 expression by Hericium Erinaceus in rat brain: relevance to Alzheimer's disease pathogenesis.

PubMed

Trovato, A; Siracusa, R; Di Paola, R; Scuto, M; Ontario, M L; Bua, Ornella; Di Mauro, Paola; Toscano, M A; Petralia, C C T; Maiolino, L; Serra, A; Cuzzocrea, S; Calabrese, Vittorio

2016-01-01

There has been a recent upsurge of interest in complementary medicine, especially dietary supplements and foods functional in delaying the onset of age-associated neurodegenerative diseases. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as antitumor, antioxidant, antiviral, antibacterial and hepatoprotective agent also capable to stimulate host immune responses. Here we provide evidence of neuroprotective action of Hericium Herinaceus when administered orally to rat. Expression of Lipoxin A4 (LXA4) was measured in different brain regions after oral administration of a biomass Hericium preparation, given for 3 month. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, Heme oxygenase -1 and Thioredoxin. In the brain of rats receiving Hericium, maximum induction of LXA4 was observed in cortex, and hippocampus followed by substantia Nigra, striatum and cerebellum. Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is a fundamental cause in neurodegenerative diseases. As prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a neurohormetic potential target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and Lipoxin A4. Emerging interest is now focussing on molecules capable of activating the vitagene system as novel therapeutic target to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. LXA4 is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. In addition, Hsp system is emerging as key pathway for modulation to prevent neuronal dysfunction, caused by protein misfolding. Conceivably, activation of LXA4 signaling and modulation of stress responsive vitagene proteins could serve as a potential therapeutic target for AD-related inflammation and neurodegenerative damage.

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

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

Lee, Katrina, E-mail: Trinabena23@gmail.com; Lenards, Nishele; Holson, Janice

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to themore » hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.« less

The AMPA receptor potentiator Org 26576 modulates stress-induced transcription of BDNF isoforms in rat hippocampus.

PubMed

Fumagalli, Fabio; Calabrese, Francesca; Luoni, Alessia; Shahid, Mohammed; Racagni, Giorgio; Riva, Marco A

2012-02-01

Brain derived neurotrophic factor (BDNF) is a key mediator of brain plasticity. The modulation of its expression and function is important for cognition and represents a key strategy to enhance neuronal resilience. Within this context, there exists a close interaction between glutamatergic neurotransmission and BDNF activity towards regulating cellular homeostasis and plasticity. The aim of the current study was to investigate the ability of the AMPA receptor potentiator Org 26576 to modulate BDNF expression in selected brain regions under basal conditions or in response to an acute swim stress. Rats subjected to a single intraperitoneal injection with Org 26576 (10mg/kg) or saline were exposed to a swim stress session (5 min) and sacrificed 15 min after the end of stress. Real-time PCR assay was used to determine changes in BDNF transcription in different brain regions. Total BDNF mRNA levels were significantly increased in the hippocampus of animals exposed to the combination of Org 26576 and stress whereas, in prefrontal and frontal cortices, BDNF mRNA levels were modulated by the acute stress, independently from drug treatment. The analysis of BDNF transcripts in the hippocampus revealed a major contribution of exons I and IV. Our results suggest that AMPA receptor potentiation by Org 26576 exerts a positive modulatory influence on BDNF expression during ongoing neuronal activity. Given that these mechanisms are critical for neuronal plasticity, we hypothesized that such changes may facilitate learning/coping mechanisms associated with a mild stressful experience. Copyright © 2011 Elsevier Ltd. All rights reserved.

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.

ViRPET--combination of virtual reality and PET brain imaging

DOEpatents

Majewski, Stanislaw; Brefczynski-Lewis, Julie

2017-05-23

Various methods, systems and apparatus are provided for brain imaging during virtual reality stimulation. In one example, among others, a system for virtual ambulatory environment brain imaging includes a mobile brain imager configured to obtain positron emission tomography (PET) scans of a subject in motion, and a virtual reality (VR) system configured to provide one or more stimuli to the subject during the PET scans. In another example, a method for virtual ambulatory environment brain imaging includes providing stimulation to a subject through a virtual reality (VR) system; and obtaining a positron emission tomography (PET) scan of the subject while moving in response to the stimulation from the VR system. The mobile brain imager can be positioned on the subject with an array of imaging photodetector modules distributed about the head of the subject.

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.

Neural Processing of Calories in Brain Reward Areas Can be Modulated by Reward Sensitivity

PubMed Central

van Rijn, Inge; Griffioen-Roose, Sanne; de Graaf, Cees; Smeets, Paul A. M.

2016-01-01

A food's reward value is dependent on its caloric content. Furthermore, a food's acute reward value also depends on hunger state. The drive to obtain rewards (reward sensitivity), however, differs between individuals. Here, we assessed the association between brain responses to calories in the mouth and trait reward sensitivity in different hunger states. Firstly, we assessed this in data from a functional neuroimaging study (van Rijn et al., 2015), in which participants (n = 30) tasted simple solutions of a non-caloric sweetener with or without a non-sweet carbohydrate (maltodextrin) during hunger and satiety. Secondly, we expanded these analyses to regular drinks by assessing the same relationship in data from a study in which soft drinks sweetened with either sucrose or a non-caloric sweetener were administered during hunger (n = 18) (Griffioen-Roose et al., 2013). First, taste activation by the non-caloric solution/soft drink was subtracted from that by the caloric solution/soft drink to eliminate sweetness effects and retain activation induced by calories. Subsequently, this difference in taste activation was correlated with reward sensitivity as measured with the BAS drive subscale of the Behavioral Activation System (BAS) questionnaire. When participants were hungry and tasted calories from the simple solution, brain activation in the right ventral striatum (caudate), right amygdala and anterior cingulate cortex (bilaterally) correlated negatively with BAS drive scores. In contrast, when participants were satiated, taste responses correlated positively with BAS drive scores in the left caudate. These results were not replicated for soft drinks. Thus, neural responses to oral calories from maltodextrin were modulated by reward sensitivity in reward-related brain areas. This was not the case for sucrose. This may be due to the direct detection of maltodextrin, but not sucrose in the oral cavity. Also, in a familiar beverage, detection of calories per se may be overruled by a conditioned response to its flavor. In conclusion, the brain reward response to calories from a long chain starch sugar (maltodextrin) varies with trait reward sensitivity. The absence of this effect in a familiar beverage warrants further research into its relevance for real life ingestive behavior. PMID:26834598

Fetal asphyctic preconditioning modulates the acute cytokine response thereby protecting against perinatal asphyxia in neonatal rats.

PubMed

Vlassaks, Evi; Strackx, Eveline; Vles, Johan Sh; Nikiforou, Maria; Martinez-Martinez, Pilar; Kramer, Boris W; Gavilanes, Antonio Wd

2013-01-26

Perinatal asphyxia (PA) is a major cause of brain damage and neurodevelopmental impairment in infants. Recent investigations have shown that experimental sublethal fetal asphyxia (FA preconditioning) protects against a subsequent more severe asphyctic insult at birth. The molecular mechanisms of this protection have, however, not been elucidated. Evidence implicates that inflammatory cytokines play a protective role in the induction of ischemic tolerance in the adult brain. Accordingly, we hypothesize that FA preconditioning leads to changes in the fetal cytokine response, thereby protecting the newborn against a subsequent asphyctic insult. In rats, FA preconditioning was induced at embryonic day 17 by clamping the uterine vasculature for 30 min. At term birth, global PA was induced by placing the uterine horns, containing the pups, in a saline bath for 19 min. We assessed, at different time points after FA and PA, mRNA and protein expression of several cytokines and related receptor mRNA levels in total hemispheres of fetal and neonatal brains. Additionally, we measured pSTAT3/STAT3 levels to investigate cellular responses to these cytokines. Prenatally, FA induced acute downregulation in IL-1β, TNF-α and IL-10 mRNA levels. At 96 h post FA, IL-6 mRNA and IL-10 protein expression were increased in FA brains compared with controls. Two hours after birth, all proinflammatory cytokines and pSTAT3/STAT3 levels decreased in pups that experienced FA and/or PA. Interestingly, IL-10 and IL-6 mRNA levels increased after PA. When pups were FA preconditioned, however, IL-10 and IL-6 mRNA levels were comparable to those in controls. FA leads to prenatal changes in the neuroinflammatory response. This modulation of the cytokine response probably results in the protective inflammatory phenotype seen when combining FA and PA and may have significant implications for preventing post-asphyctic perinatal encephalopathy.

Fetal asphyctic preconditioning modulates the acute cytokine response thereby protecting against perinatal asphyxia in neonatal rats

PubMed Central

2013-01-01

Background Perinatal asphyxia (PA) is a major cause of brain damage and neurodevelopmental impairment in infants. Recent investigations have shown that experimental sublethal fetal asphyxia (FA preconditioning) protects against a subsequent more severe asphyctic insult at birth. The molecular mechanisms of this protection have, however, not been elucidated. Evidence implicates that inflammatory cytokines play a protective role in the induction of ischemic tolerance in the adult brain. Accordingly, we hypothesize that FA preconditioning leads to changes in the fetal cytokine response, thereby protecting the newborn against a subsequent asphyctic insult. Methods In rats, FA preconditioning was induced at embryonic day 17 by clamping the uterine vasculature for 30 min. At term birth, global PA was induced by placing the uterine horns, containing the pups, in a saline bath for 19 min. We assessed, at different time points after FA and PA, mRNA and protein expression of several cytokines and related receptor mRNA levels in total hemispheres of fetal and neonatal brains. Additionally, we measured pSTAT3/STAT3 levels to investigate cellular responses to these cytokines. Results Prenatally, FA induced acute downregulation in IL-1β, TNF-α and IL-10 mRNA levels. At 96 h post FA, IL-6 mRNA and IL-10 protein expression were increased in FA brains compared with controls. Two hours after birth, all proinflammatory cytokines and pSTAT3/STAT3 levels decreased in pups that experienced FA and/or PA. Interestingly, IL-10 and IL-6 mRNA levels increased after PA. When pups were FA preconditioned, however, IL-10 and IL-6 mRNA levels were comparable to those in controls. Conclusions FA leads to prenatal changes in the neuroinflammatory response. This modulation of the cytokine response probably results in the protective inflammatory phenotype seen when combining FA and PA and may have significant implications for preventing post-asphyctic perinatal encephalopathy. PMID:23351591

Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states.

PubMed

Lecrux, C; Hamel, E

2016-10-05

Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways. The neural circuits recruited by whisker glutamatergic-, basal forebrain cholinergic- or locus coeruleus noradrenergic pathway stimulation were found to be highly specific and discriminative, particularly when comparing the two modulatory systems to the sensory response. However, it is largely unknown whether or not NVC is still reliable when brain states are altered or in disease conditions. This lack of knowledge is surprising since brain imaging is broadly used in humans and, ultimately, in conditions that deviate from baseline brain function. Using the whisker-to-barrel pathway as a model of NVC, we can interrogate the reliability of NVC under enhanced cholinergic or noradrenergic modulation of cortical circuits that alters brain states.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. © 2016 The Author(s).

Sensitivity of human auditory cortex to rapid frequency modulation revealed by multivariate representational similarity analysis.

PubMed

Joanisse, Marc F; DeSouza, Diedre D

2014-01-01

Functional Magnetic Resonance Imaging (fMRI) was used to investigate the extent, magnitude, and pattern of brain activity in response to rapid frequency-modulated sounds. We examined this by manipulating the direction (rise vs. fall) and the rate (fast vs. slow) of the apparent pitch of iterated rippled noise (IRN) bursts. Acoustic parameters were selected to capture features used in phoneme contrasts, however the stimuli themselves were not perceived as speech per se. Participants were scanned as they passively listened to sounds in an event-related paradigm. Univariate analyses revealed a greater level and extent of activation in bilateral auditory cortex in response to frequency-modulated sweeps compared to steady-state sounds. This effect was stronger in the left hemisphere. However, no regions showed selectivity for either rate or direction of frequency modulation. In contrast, multivoxel pattern analysis (MVPA) revealed feature-specific encoding for direction of modulation in auditory cortex bilaterally. Moreover, this effect was strongest when analyses were restricted to anatomical regions lying outside Heschl's gyrus. We found no support for feature-specific encoding of frequency modulation rate. Differential findings of modulation rate and direction of modulation are discussed with respect to their relevance to phonetic discrimination.

Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

PubMed

Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S

2018-01-01

Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

Effects of expectancy and abstinence on the neural response to smoking cues in cigarette smokers: an fMRI study.

PubMed

McBride, Dharma; Barrett, Sean P; Kelly, Jared T; Aw, Andrew; Dagher, Alain

2006-12-01

Cues associated with drug taking can trigger relapse, drug seeking, and craving in addicted individuals. Behavioral studies suggest that drug availability and withdrawal can affect the individual response to drug cues. Moreover, the importance of subjective craving in cue-induced relapse has been questioned and an alternative model put forward according to which drug cues trigger habitual drug-seeking behaviors independently of craving. We used functional magnetic resonance imaging to compare the brain response to smoking and control videotapes in 20 healthy smokers, while varying their expectancy to smoke and abstinence levels. The neural response to cigarette cues was strongly modulated by expectancy and, to a lesser extent, abstinence. In people expecting to smoke immediately after the scan, smoking cues activated brain areas implicated in arousal, attention, and cognitive control. However, when subjects knew they would not be allowed to smoke for 4 h, there was almost no brain activation in response to smoking cues, despite equivalent reported levels of craving. In the dorsolateral prefrontal cortex, the neural response was a function of both craving and expectancy. Thalamo-cingulate connectivity, thought to be an index of arousal, was greater during expectancy than nonexpectancy. Our findings confirm the importance of expectancy in the neural response to drug cues, and lend support to the theory that these cues act on brain areas involved in arousal and attention.

Angiotensin II and the transcription factor Rel/NF-kappaB link environmental water shortage with memory improvement.

PubMed

Frenkel, L; Freudenthal, R; Romano, A; Nahmod, V E; Maldonado, H; Delorenzi, A

2002-01-01

One of the essential requirements even in the most ancient life forms is to be able to preserve body fluid medium. In line with such requirement, animals need to perform different behaviors to cope with water shortages. As angiotensin II (ANGII) is involved on a widespread range of functions in vertebrates, including memory modulation, an integrative role, in response to an environmental water shortage, has been envisioned. Previous work on the semi-terrestrial and brackish-water crab Chasmagnathus granulatus showed that endogenous ANGII enhanced an associative long-term memory and, in addition, that high salinity environment induces both an increase of brain ANGII levels and memory improvement. Here, we show that in the crab Chasmagnathus air exposure transiently increases blood sodium concentration, significantly increases brain ANGII immunoreactivity, and has a facilitatory effect on memory that is abolished by a non-selective ANGII receptor antagonist, saralasin. Furthermore, Rel/NF-kappaB, a transcription factor activated by ANGII in mammals and during memory consolidation in Chasmagnathus brain, is induced in the crab's brain by air exposure. Moreover, nuclear brain NF-kappaB is activated by ANGII, and this effect is reversed by saralasin. Our results constitute the first demonstration in an invertebrate that cognitive functions are modulated by an environmental stimulus through a neuropeptide and give evolutionary support to the role of angiotensins in memory processes. Moreover, these results suggest that angiotensinergic system is preserved across evolution not only in its structure and molecular mechanisms, but also in its capability of coordinating specific adaptative responses.

BMI not WHR modulates BOLD fMRI responses in a sub-cortical reward network when participants judge the attractiveness of human female bodies.

PubMed

Holliday, Ian E; Longe, Olivia A; Thai, N Jade; Hancock, Peter J B; Tovée, Martin J

2011-01-01

In perceptual terms, the human body is a complex 3d shape which has to be interpreted by the observer to judge its attractiveness. Both body mass and shape have been suggested as strong predictors of female attractiveness. Normally body mass and shape co-vary, and it is difficult to differentiate their separate effects. A recent study suggested that altering body mass does not modulate activity in the reward mechanisms of the brain, but shape does. However, using computer generated female body-shaped greyscale images, based on a Principal Component Analysis of female bodies, we were able to construct images which covary with real female body mass (indexed with BMI) and not with body shape (indexed with WHR), and vice versa. Twelve observers (6 male and 6 female) rated these images for attractiveness during an fMRI study. The attractiveness ratings were correlated with changes in BMI and not WHR. Our primary fMRI results demonstrated that in addition to activation in higher visual areas (such as the extrastriate body area), changing BMI also modulated activity in the caudate nucleus, and other parts of the brain reward system. This shows that BMI, not WHR, modulates reward mechanisms in the brain and we infer that this may have important implications for judgements of ideal body size in eating disordered individuals.

BMI Not WHR Modulates BOLD fMRI Responses in a Sub-Cortical Reward Network When Participants Judge the Attractiveness of Human Female Bodies

PubMed Central

Holliday, Ian E.; Longe, Olivia A.; Thai, N. Jade; Hancock, Peter J. B.; Tovée, Martin J.

2011-01-01

In perceptual terms, the human body is a complex 3d shape which has to be interpreted by the observer to judge its attractiveness. Both body mass and shape have been suggested as strong predictors of female attractiveness. Normally body mass and shape co-vary, and it is difficult to differentiate their separate effects. A recent study suggested that altering body mass does not modulate activity in the reward mechanisms of the brain, but shape does. However, using computer generated female body-shaped greyscale images, based on a Principal Component Analysis of female bodies, we were able to construct images which covary with real female body mass (indexed with BMI) and not with body shape (indexed with WHR), and vice versa. Twelve observers (6 male and 6 female) rated these images for attractiveness during an fMRI study. The attractiveness ratings were correlated with changes in BMI and not WHR. Our primary fMRI results demonstrated that in addition to activation in higher visual areas (such as the extrastriate body area), changing BMI also modulated activity in the caudate nucleus, and other parts of the brain reward system. This shows that BMI, not WHR, modulates reward mechanisms in the brain and we infer that this may have important implications for judgements of ideal body size in eating disordered individuals. PMID:22102883

Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women.

PubMed

Li, Bingbing; Cheng, Gang; Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

2016-01-01

Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects' Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and perspective taking ability.

Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women

PubMed Central

Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

2016-01-01

Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p < 0.005 uncorrected. Furthermore, the level of the test subjects’ Interest-In-Infants was positively associated with the intensity of right fusiform gyrus response to infant faces and uncomfortable infant faces compared to sad adult faces. In addition, the Perspective Taking subscale score on the Interpersonal Reactivity Index-Chinese was significantly correlated with precuneus activity during uncomfortable infant faces compared to sad adult faces. Our findings suggest that regional brain areas may bias cognitive and emotional responses to infant facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and perspective taking ability. PMID:27977692

Social cognition in members of conflict groups: behavioural and neural responses in Arabs, Israelis and South Americans to each other's misfortunes.

PubMed

Bruneau, Emile G; Dufour, Nicholas; Saxe, Rebecca

2012-03-05

In contexts of cultural conflict, people delegitimize the other group's perspective and lose compassion for the other group's suffering. These psychological biases have been empirically characterized in intergroup settings, but rarely in groups involved in active conflict. Similarly, the basic brain networks involved in recognizing others' narratives and misfortunes have been identified, but how these brain networks are modulated by intergroup conflict is largely untested. In the present study, we examined behavioural and neural responses in Arab, Israeli and South American participants while they considered the pain and suffering of individuals from each group. Arabs and Israelis reported feeling significantly less compassion for each other's pain and suffering (the 'conflict outgroup'), but did not show an ingroup bias relative to South Americans (the 'distant outgroup'). In contrast, the brain regions that respond to others' tragedies showed an ingroup bias relative to the distant outgroup but not the conflict outgroup, particularly for descriptions of emotional suffering. Over all, neural responses to conflict group members were qualitatively different from neural responses to distant group members. This is the first neuroimaging study to examine brain responses to others' suffering across both distant and conflict groups, and provides a first step towards building a foundation for the biological basis of conflict.

Pathophysiology and Management of Parkinsonian Tremor.

PubMed

Helmich, Rick C; Dirkx, Michiel F

2017-04-01

Parkinson's tremor is one of the cardinal motor symptoms of Parkinson's disease. The pathophysiology of Parkinson's tremor is different from that of other motor symptoms such as bradykinesia and rigidity. In this review, the authors discuss evidence suggesting that tremor is a network disorder that arises from distinct pathophysiological changes in the basal ganglia and in the cerebellothalamocortical circuit. They also discuss how interventions in this circuitry, for example, deep brain surgery and noninvasive brain stimulation, can modulate or even treat tremor. Future research may focus on understanding sources for the large variability between patients in terms of treatment response, on understanding the contextual factors that modulate tremor (stress, voluntary movements), and on focused interventions in the tremor circuitry. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Polyphenols journey through blood-brain barrier towards neuronal protection.

PubMed

Figueira, I; Garcia, G; Pimpão, R C; Terrasso, A P; Costa, I; Almeida, A F; Tavares, L; Pais, T F; Pinto, P; Ventura, M R; Filipe, A; McDougall, G J; Stewart, D; Kim, K S; Palmela, I; Brites, D; Brito, M A; Brito, C; Santos, C N

2017-09-13

Age-related complications such as neurodegenerative disorders are increasing and remain cureless. The possibility of altering the progression or the development of these multifactorial diseases through diet is an emerging and attractive approach with increasing experimental support. We examined the potential of known bioavailable phenolic sulfates, arising from colonic metabolism of berries, to influence hallmarks of neurodegenerative processes. In silico predictions and in vitro transport studies across blood-brain barrier (BBB) endothelial cells, at circulating concentrations, provided evidence for differential transport, likely related to chemical structure. Moreover, endothelial metabolism of these phenolic sulfates produced a plethora of novel chemical entities with further potential bioactivies. Pre-conditioning with phenolic sulfates improved cellular responses to oxidative, excitotoxicity and inflammatory injuries and this attenuation of neuroinflammation was achieved via modulation of NF-κB pathway. Our results support the hypothesis that these small molecules, derived from dietary (poly)phenols may cross the BBB, reach brain cells, modulate microglia-mediated inflammation and exert neuroprotective effects, with potential for alleviation of neurodegenerative diseases.

Prior Consumption of a Fat Meal in Healthy Adults Modulates the Brain’s Response to Fat123

PubMed Central

Eldeghaidy, Sally; Hort, Joanne; Hollowood, Tracey; Singh, Gulzar; Bush, Debbie; Foster, Tim; Taylor, Andy J; Busch, Johanneke; Spiller, Robin C

2016-01-01

Background: The consumption of fat is regulated by reward and homeostatic pathways, but no studies to our knowledge have examined the role of high-fat meal (HFM) intake on subsequent brain activation to oral stimuli. Objective: We evaluated how prior consumption of an HFM or water load (WL) modulates reward, homeostatic, and taste brain responses to the subsequent delivery of oral fat. Methods: A randomized 2-way crossover design spaced 1 wk apart was used to compare the prior consumption of a 250-mL HFM (520 kcal) [rapeseed oil (440 kcal), emulsifier, sucrose, flavor cocktail] or noncaloric WL on brain activation to the delivery of repeated trials of a flavored no-fat control stimulus (CS) or flavored fat stimulus (FS) in 17 healthy adults (11 men) aged 25 ± 2 y and with a body mass index (in kg/m2) of 22.4 ± 0.8. We tested differences in brain activation to the CS and FS and baseline cerebral blood flow (CBF) after the HFM and WL. We also tested correlations between an individual’s plasma cholecystokinin (CCK) concentration after the HFM and blood oxygenation level–dependent (BOLD) activation of brain regions. Results: Compared to the WL, consuming the HFM led to decreased anterior insula taste activation in response to both the CS (36.3%; P < 0.05) and FS (26.5%; P < 0.05). The HFM caused reduced amygdala activation (25.1%; P < 0.01) in response to the FS compared to the CS (fat-related satiety). Baseline CBF significantly reduced in taste (insula: 5.7%; P < 0.01), homeostatic (hypothalamus: 9.2%, P < 0.01; thalamus: 5.1%, P < 0.05), and reward areas (striatum: 9.2%; P < 0.01) after the HFM. An individual’s plasma CCK concentration correlated negatively with brain activation in taste and oral somatosensory (ρ = −0.39; P < 0.05) and reward areas (ρ = −0.36; P < 0.05). Conclusions: Our results in healthy adults show that an HFM suppresses BOLD activation in taste and reward areas compared to a WL. This understanding will help inform the reformulation of reduced-fat foods that mimic the brain’s response to high-fat counterparts and guide future interventions to reduce obesity. PMID:27655761

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

Polysaccharides from Ganoderma lucidum attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis and behavioural response.

PubMed

Cai, Qing; Li, Yuanyuan; Pei, Gang

2017-03-24

Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated. Further, GLP effect on microglial behavioural modulations in correlation with the inflammatory responses remains to be unravelled. The aim of this work was to quantitatively analyse the contributions of GLP on microglia. The BV2 microglia and primary mouse microglia were stimulated by lipopolysaccharides (LPS) and amyloid beta 42 (Aβ 42 ) oligomer, respectively. Investigation on the effect of GLP was carried by quantitative determination of the microglial pro- and anti-inflammatory cytokine expressions and behavioural modulations including migration, morphology and phagocytosis. Analysis of microglial morphology and phagocytosis modulations was confirmed in the zebrafish brain. Quantitative results revealed that GLP down-regulates LPS- or Aβ-induced pro-inflammatory cytokines and promotes anti-inflammatory cytokine expressions in BV-2 and primary microglia. In addition, GLP attenuates inflammation-related microglial migration, morphological alterations and phagocytosis probabilities. We also showed that modulations of microglial behavioural responses were associated with MCP-1 and C1q expressions. Overall, our study provides an insight into the GLP regulation of LPS- and Aβ-induced neuroinflammation and serves an implication that the neuroprotective function of GLP might be achieved through modulation of microglial inflammatory and behavioural responses.

Impaired early visual response modulations to spatial information in chronic schizophrenia

PubMed Central

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

2011-01-01

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

AT1 and AT2 Receptors in the Prelimbic Cortex Modulate the Cardiovascular Response Evoked by Acute Exposure to Restraint Stress in Rats.

PubMed

Brasil, Taíz F S; Fassini, Aline; Corrêa, Fernando M

2018-01-01

The prelimbic cortex (PL) is an important structure in the neural pathway integrating stress responses. Brain angiotensin is involved in cardiovascular control and modulation of stress responses. Blockade of angiotensin receptors has been reported to reduce stress responses. Acute restraint stress (ARS) is a stress model, which evokes sustained blood pressure increase, tachycardia, and reduction in tail temperature. We therefore hypothesized that PL locally generated angiotensin and angiotensin receptors modulate stress autonomic responses. To test this hypothesis, we microinjected an angiotensin-converting enzyme (ACE) inhibitor or angiotensin antagonists into the PL, prior to ARS. Male Wistar rats were used; guide cannulas were bilaterally implanted in the PL for microinjection of vehicle or drugs. A polyethylene catheter was introduced into the femoral artery to record cardiovascular parameters. Tail temperature was measured using a thermal camera. ARS was started 10 min after PL treatment with drugs. Pretreatment with ACE inhibitor lisinopril (0.5 nmol/100 nL) reduced the pressor response, but did not affect ARS-evoked tachycardia. At a dose of 1 nmol/100 nL, it reduced both ARS pressor and tachycardic responses. Pretreatment with candesartan, AT1 receptor antagonist reduced ARS-evoked pressor response, but not tachycardia. Pretreatment with PD123177, AT2 receptor antagonist, reduced tachycardia, but did not affect ARS pressor response. No treatment affected ARS fall in tail temperature. Results suggest involvement of PL angiotensin in the mediation of ARS cardiovascular responses, with participation of both AT1 and AT2 receptors. In conclusion, results indicate that PL AT1-receptors modulate the ARS-evoked pressor response, while AT2-receptors modulate the tachycardic component of the autonomic response.

Peripheral Tumor Necrosis Factor-Alpha (TNF-α) Modulates Amyloid Pathology by Regulating Blood-Derived Immune Cells and Glial Response in the Brain of AD/TNF Transgenic Mice.

PubMed

Paouri, Evi; Tzara, Ourania; Kartalou, Georgia-Ioanna; Zenelak, Sofia; Georgopoulos, Spiros

2017-05-17

Increasing evidence has suggested that systemic inflammation along with local brain inflammation can play a significant role in Alzheimer's disease (AD) pathogenesis. Identifying key molecules that regulate the crosstalk between the immune and the CNS can provide potential therapeutic targets. TNF-α is a proinflammatory cytokine implicated in the pathogenesis of systemic inflammatory and neurodegenerative diseases, such as rheumatoid arthritis (RA) and AD. Recent studies have reported that anti-TNF-α therapy or RA itself can modulate AD pathology, although the underlying mechanism is unclear. To investigate the role of peripheral TNF-α as a mediator of RA in the pathogenesis of AD, we generated double-transgenic 5XFAD/Tg197 AD/TNF mice that develop amyloid deposits and inflammatory arthritis induced by human TNF-α (huTNF-α) expression. We found that 5XFAD/Tg197 mice display decreased amyloid deposition, compromised neuronal integrity, and robust brain inflammation characterized by extensive gliosis and elevated blood-derived immune cell populations, including phagocytic macrophages and microglia. To evaluate the contribution of peripheral huTNF-α in the observed brain phenotype, we treated 5XFAD/Tg197 mice systemically with infliximab, an anti-huTNF-α antibody that does not penetrate the blood-brain barrier and prevents arthritis. Peripheral inhibition of huTNF-α increases amyloid deposition, rescues neuronal impairment, and suppresses gliosis and recruitment of blood-derived immune cells, without affecting brain huTNF-α levels. Our data report, for the first time, a distinctive role for peripheral TNF-α in the modulation of the amyloid phenotype in mice by regulating blood-derived and local brain inflammatory cell populations involved in β-amyloid clearance. SIGNIFICANCE STATEMENT Mounting evidence supports the active involvement of systemic inflammation, in addition to local brain inflammation, in Alzheimer's disease (AD) progression. TNF-α is a pluripotent cytokine that has been independently involved in the pathogenesis of systemic inflammatory rheumatoid arthritis (RA) and AD. Here we first demonstrate that manipulation of peripheral TNF-α in the context of arthritis modulates the amyloid phenotype by regulating immune cell trafficking in the mouse brain. Our study suggests that additionally to its local actions in the AD brain, TNF-α can also indirectly modulate amyloid pathology as a regulator of peripheral inflammation. Our findings may have significant implications in the treatment of RA patients with anti-TNF-α drugs and in the potential use of TNF-targeted therapies for AD. Copyright © 2017 the authors 0270-6474/17/375155-17$15.00/0.

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma

PubMed Central

Wood, JodiAnne T.; Williams, John S.; Pandarinathan, Lakshmipathi; Janero, David R.; Lammi-Keefe, Carol J.; Makriyannis, Alexandros

2010-01-01

The endocannabinoid metabolome consists of a growing, (patho)physiologically important family of fatty-acid derived signaling lipids. Diet is a major source of fatty acid substrate for mammalian endocannabinoid biosynthesis. The principal long-chain PUFA found in mammalian brain, docosahexaenoic acid (DHA), supports neurological function, retinal development, and overall health. The extent to which dietary DHA supplementation influences endocannabinoid-related metabolites in brain, within the context of the circulating endocannabinoid profile, is currently unknown. We report the first lipidomic analysis of acute 2-week DHA dietary supplementation effects on the physiological state of 15 fatty-acid, N-acylethanolamine, and glycerol-ester endocannabinoid metabolome constituents in murine plasma and brain. The DHA-rich diet markedly elevated DHA, eicosapentaenoic acid, 2-eicosapentanoylglycerol (EPG), and docosahexanoylethanolamine in both compartments. Dietary DHA enhancement generally affected the synthesis of the N-acyl-ethanolamine and glycerol-ester metabolites to favor the docosahexaenoic and eicosapentaenoic vs. arachidonoyl and oleoyl homologs in both brain and plasma. The greater overall responsiveness of the endocannabinoid metabolome in plasma versus brain may reflect a more circumscribed homeostatic response range of brain lipids to dietary DHA supplementation. The ability of short-term DHA enhancement to modulate select constituents of the physiological brain and plasma endocannabinoid metabolomes carries metabolic and therapeutic implications. PMID:20071693

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma.

PubMed

Wood, Jodianne T; Williams, John S; Pandarinathan, Lakshmipathi; Janero, David R; Lammi-Keefe, Carol J; Makriyannis, Alexandros

2010-06-01

The endocannabinoid metabolome consists of a growing, (patho)physiologically important family of fatty-acid derived signaling lipids. Diet is a major source of fatty acid substrate for mammalian endocannabinoid biosynthesis. The principal long-chain PUFA found in mammalian brain, docosahexaenoic acid (DHA), supports neurological function, retinal development, and overall health. The extent to which dietary DHA supplementation influences endocannabinoid-related metabolites in brain, within the context of the circulating endocannabinoid profile, is currently unknown. We report the first lipidomic analysis of acute 2-week DHA dietary supplementation effects on the physiological state of 15 fatty-acid, N-acylethanolamine, and glycerol-ester endocannabinoid metabolome constituents in murine plasma and brain. The DHA-rich diet markedly elevated DHA, eicosapentaenoic acid, 2-eicosapentanoylglycerol (EPG), and docosahexanoylethanolamine in both compartments. Dietary DHA enhancement generally affected the synthesis of the N-acyl-ethanolamine and glycerol-ester metabolites to favor the docosahexaenoic and eicosapentaenoic vs. arachidonoyl and oleoyl homologs in both brain and plasma. The greater overall responsiveness of the endocannabinoid metabolome in plasma versus brain may reflect a more circumscribed homeostatic response range of brain lipids to dietary DHA supplementation. The ability of short-term DHA enhancement to modulate select constituents of the physiological brain and plasma endocannabinoid metabolomes carries metabolic and therapeutic implications.

Particulate matter triggers depressive-like response associated with modulation of inflammatory cytokine homeostasis and brain-derived neurotrophic factor signaling pathway in mice.

PubMed

Liu, Xuemei; Qian, Xin; Xing, Jing; Wang, Jinhua; Sun, Yixuan; Wang, Qin'geng; Li, Huiming

2018-04-23

Particulate matter (PM) exposure may contribute to depressive-like response in mice. However, few studies have evaluated the adaptive impacts of long-term PM exposure on depressive-like response associated with systemic inflammation and brain-derived neurotrophic factor (BDNF) signaling pathway. We studied the association among depressive-like behaviors, mRNA levels of pro- and anti-inflammatory cytokines, and the expression of BDNF signaling pathway in mice by long-term PM exposure. C57BL/6 male mice were exposed to ambient air alongside control mice breathing air filtered through a high-efficiency air PM (HEPA) filter. Depressive-like behaviors were assessed together with pro-inflammatory, anti-inflammatory cytokine mRNA levels and the modulation of BDNF pathway in hippocampus and olfactory-bulb of mice exposed to PM for 4, 8, and 12 weeks. Exposure to HEPA filtered air for 4 weeks may exert antidepressant like effects in mice. Pro-inflammatory cytokines were up-regulated while the expression of BDNF, its high-affinity receptor tropomyosin-related kinase B (TrkB), and the transcription factor cAMP-response-element binding protein (CREB) were down-regulated in ambient air mice. However, after 8 weeks, there was no significant difference in the rate of depressive-like behaviors between the two groups. After 12 weeks, mice exposed to ambient air again had a higher rate of depressive-like behaviors, significant up-regulation of pro-inflammatory cytokines, down-regulation of interleukin-10 (IL-10), BDNF, TrkB, and CREB than HEPA mice. Ultrafine PM in brain tissues of mice exposed to ambient air was observed. Our results suggest continuous high-level PM exposure alters the depressive-like response in mice and induces a damage-repair-imbalance reaction.

H2S Regulates Hypobaric Hypoxia-Induced Early Glio-Vascular Dysfunction and Neuro-Pathophysiological Effects

PubMed Central

Kumar, Gaurav; Chhabra, Aastha; Mishra, Shalini; Kalam, Haroon; Kumar, Dhiraj; Meena, Ramniwas; Ahmad, Yasmin; Bhargava, Kalpana; Prasad, Dipti N.; Sharma, Manish

2016-01-01

Hypobaric Hypoxia (HH) is an established risk factor for various neuro-physiological perturbations including cognitive impairment. The origin and mechanistic basis of such responses however remain elusive. We here combined systems level analysis with classical neuro-physiological approaches, in a rat model system, to understand pathological responses of brain to HH. Unbiased ‘statistical co-expression networks’ generated utilizing temporal, differential transcriptome signatures of hippocampus—centrally involved in regulating cognition—implicated perturbation of Glio-Vascular homeostasis during early responses to HH, with concurrent modulation of vasomodulatory, hemostatic and proteolytic processes. Further, multiple lines of experimental evidence from ultra-structural, immuno-histological, substrate-zymography and barrier function studies unambiguously supported this proposition. Interestingly, we show a significant lowering of H2S levels in the brain, under chronic HH conditions. This phenomenon functionally impacted hypoxia-induced modulation of cerebral blood flow (hypoxic autoregulation) besides perturbing the strength of functional hyperemia responses. The augmentation of H2S levels, during HH conditions, remarkably preserved Glio-Vascular homeostasis and key neuro-physiological functions (cerebral blood flow, functional hyperemia and spatial memory) besides curtailing HH-induced neuronal apoptosis in hippocampus. Our data thus revealed causal role of H2S during HH-induced early Glio-Vascular dysfunction and consequent cognitive impairment. PMID:27211559

Cytokine Immunopathogenesis of Enterovirus 71 Brain Stem Encephalitis

PubMed Central

Wang, Shih-Min; Lei, Huan-Yao; Liu, Ching-Chuan

2012-01-01

Enterovirus 71 (EV71) is one of the most important causes of herpangina and hand, foot, and mouth disease. It can also cause severe complications of the central nervous system (CNS). Brain stem encephalitis with pulmonary edema is the severe complication that can lead to death. EV71 replicates in leukocytes, endothelial cells, and dendritic cells resulting in the production of immune and inflammatory mediators that shape innate and acquired immune responses and the complications of disease. Cytokines, as a part of innate immunity, favor the development of antiviral and Th1 immune responses. Cytokines and chemokines play an important role in the pathogenesis EV71 brain stem encephalitis. Both the CNS and the systemic inflammatory responses to infection play important, but distinctly different, roles in the pathogenesis of EV71 pulmonary edema. Administration of intravenous immunoglobulin and milrinone, a phosphodiesterase inhibitor, has been shown to modulate inflammation, to reduce sympathetic overactivity, and to improve survival in patients with EV71 autonomic nervous system dysregulation and pulmonary edema. PMID:22956971

Molecular changes in brain aging and Alzheimer’s disease are mirrored in experimentally silenced cortical neuron networks

PubMed Central

Gleichmann, Marc; Zhang, Yongqing; Wood, William H.; Becker, Kevin G.; Mughal, Mohamed R.; Pazin, Michael J.; van Praag, Henriette; Kobilo, Tali; Zonderman, Alan B.; Troncoso, Juan C.; Markesbery, William R.; Mattson, Mark P.

2010-01-01

Activity-dependent modulation of neuronal gene expression promotes neuronal survival and plasticity, and neuronal network activity is perturbed in aging and Alzheimer’s disease (AD). Here we show that cerebral cortical neurons respond to chronic suppression of excitability by downregulating the expression of genes and their encoded proteins involved in inhibitory transmission (GABAergic and somatostatin) and Ca2+ signaling; alterations in pathways involved in lipid metabolism and energy management are also features of silenced neuronal networks. A molecular fingerprint strikingly similar to that of diminished network activity occurs in the human brain during aging and in AD, and opposite changes occur in response to activation of N-methyl-D-aspartate (NMDA) and brain-derived neurotrophic factor (BDNF) receptors in cultured cortical neurons and in mice in response to an enriched environment or electroconvulsive shock. Our findings suggest that reduced inhibitory neurotransmission during aging and in AD may be the result of compensatory responses that, paradoxically, render the neurons vulnerable to Ca2+-mediated degeneration. PMID:20947216

Hepatic expression of serum amyloid A1 is induced by traumatic brain injury and modulated by telmisartan.

PubMed

Villapol, Sonia; Kryndushkin, Dmitry; Balarezo, Maria G; Campbell, Ashley M; Saavedra, Juan M; Shewmaker, Frank P; Symes, Aviva J

2015-10-01

Traumatic brain injury affects the whole body in addition to the direct impact on the brain. The systemic response to trauma is associated with the hepatic acute-phase response. To further characterize this response, we performed controlled cortical impact injury on male mice and determined the expression of serum amyloid A1 (SAA1), an apolipoprotein, induced at the early stages of the acute-phase response in liver and plasma. After cortical impact injury, induction of SAA1 was detectable in plasma at 6 hours post-injury and in liver at 1 day post-injury, followed by gradual diminution over time. In the liver, cortical impact injury increased neutrophil and macrophage infiltration, apoptosis, and expression of mRNA encoding the chemokines CXCL1 and CXCL10. An increase in angiotensin II AT1 receptor mRNA at 3 days post-injury was also observed. Administration of the AT1 receptor antagonist telmisartan 1 hour post-injury significantly decreased liver SAA1 levels and CXCL10 mRNA expression, but did not affect CXCL1 expression or the number of apoptotic cells or infiltrating leukocytes. To our knowledge, this is the first study to demonstrate that SAA1 is induced in the liver after traumatic brain injury and that telmisartan prevents this response. Elucidating the molecular pathogenesis of the liver after brain injury will assist in understanding the efficacy of therapeutic approaches to brain injury. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

N-butyldeoxynojirimycin treatment restores the innate fear response and improves learning in mucopolysaccharidosis IIIA mice.

PubMed

Kaidonis, Xenia; Byers, Sharon; Ranieri, Enzo; Sharp, Peter; Fletcher, Janice; Derrick-Roberts, Ainslie

2016-06-01

Mucopolysaccharidosis IIIA is a heritable neurodegenerative disorder resulting from the dysfunction of the lysosomal hydrolase sulphamidase. This leads to the primary accumulation of the complex carbohydrate heparan sulphate in a wide range of tissues and the secondary neuronal storage of gangliosides GM2 and GM3 in the brain. GM2 storage is associated with CNS deterioration in the GM2 gangliosidosis group of lysosomal storage disorders and may also contribute to MPS CNS disease. N-butyldeoxynojirimycin, an inhibitor of ceramide glucosyltransferase activity and therefore of ganglioside synthesis, was administered to MPS IIIA mice both prior to maximal GM2 and GM3 accumulation (early treatment) and after the maximum level of ganglioside had accumulated in the brain (late treatment) to determine if behaviour was altered by ganglioside level. Ceramide glucosyltransferase activity was decreased in both treatment groups; however, brain ganglioside levels were only decreased in the late treatment group. Learning in the water cross maze was improved in both groups and the innate fear response was also restored in both groups. A reduction in the expression of inflammatory gene Ccl3 was observed in the early treatment group, while IL1β expression was reduced in both treatment groups. Thus, it appears that NB-DNJ elicits a transient decrease in brain ganglioside levels, some modulation of inflammatory cytokines and a functional improvement in behaviour that can be elicited both before and after overt neurological changes manifest. NB-DNJ improves learning and restores the innate fear response in MPS IIIA mice by decreasing ceramide glucosyltransferase activity and transiently reducing ganglioside storage and/or modulating inflammatory signals. Copyright © 2016 Elsevier Inc. All rights reserved.

Dopaminergic Challenge With Bromocriptine One Month After Mild Traumatic Brain Injury: Altered Working Memory and BOLD Response

PubMed Central

McAllister, Thomas W.; Flashman, Laura A.; McDonald, Brenna C.; Ferrell, Richard B.; Tosteson, Tor D.; Yanofsky, Norman N.; Grove, Margaret R.; Saykin, Andrew J.

2014-01-01

Catecholamines, particularly dopamine, modulate working memory (WM). Altered sensitivity to dopamine might play a role in WM changes observed after traumatic brain injury (TBI). Thirty-one healthy controls (HC) and 26 individuals with mild TBI (MTBI) 1 month after injury were challenged with bromocriptine versus placebo before administration of a verbal WM functional MRI task. Bromocriptine was associated with improved WM performance in the HC but not the MTBI group. On bromocriptine, the MTBI group showed increased activation outside of a task-specific region of interest. Findings are consistent with the hypothesis that individuals with MTBI have altered responsivity to dopamine. PMID:21948888

The Microbiome-Gut-Behavior Axis: Crosstalk Between the Gut Microbiome and Oligodendrocytes Modulates Behavioral Responses.

PubMed

Ntranos, Achilles; Casaccia, Patrizia

2018-01-01

Environmental and dietary stimuli have always been implicated in brain development and behavioral responses. The gut, being the major portal of communication with the external environment, has recently been brought to the forefront of this interaction with the establishment of a gut-brain axis in health and disease. Moreover, recent breakthroughs in germ-free and antibiotic-treated mice have demonstrated the significant impact of the microbiome in modulating behavioral responses in mice and have established a more specific microbiome-gut-behavior axis. One of the mechanisms by which this axis affects social behavior is by regulating myelination at the prefrontal cortex, an important site for complex cognitive behavior planning and decision-making. The prefrontal cortex exhibits late myelination of its axonal projections that could extend into the third decade of life in humans, which make it susceptible to external influences, such as microbial metabolites. Changes in the gut microbiome were shown to alter the composition of the microbial metabolome affecting highly permeable bioactive compounds, such as p-cresol, which could impair oligodendrocyte differentiation. Dysregulated myelination in the prefrontal cortex is then able to affect behavioral responses in mice, shifting them towards social isolation. The reduced social interactions could then limit microbial exchange, which could otherwise pose a threat to the survival of the existing microbial community in the host and, thus, provide an evolutionary advantage to the specific microbial community. In this review, we will analyze the microbiome-gut-behavior axis, describe the interactions between the gut microbiome and oligodendrocytes and highlight their role in the modulation of social behavior.

Self-face recognition in social context.

PubMed

Sugiura, Motoaki; Sassa, Yuko; Jeong, Hyeonjeong; Wakusawa, Keisuke; Horie, Kaoru; Sato, Shigeru; Kawashima, Ryuta

2012-06-01

The concept of "social self" is often described as a representation of the self-reflected in the eyes or minds of others. Although the appearance of one's own face has substantial social significance for humans, neuroimaging studies have failed to link self-face recognition and the likely neural substrate of the social self, the medial prefrontal cortex (MPFC). We assumed that the social self is recruited during self-face recognition under a rich social context where multiple other faces are available for comparison of social values. Using functional magnetic resonance imaging (fMRI), we examined the modulation of neural responses to the faces of the self and of a close friend in a social context. We identified an enhanced response in the ventral MPFC and right occipitoparietal sulcus in the social context specifically for the self-face. Neural response in the right lateral parietal and inferior temporal cortices, previously claimed as self-face-specific, was unaffected for the self-face but unexpectedly enhanced for the friend's face in the social context. Self-face-specific activation in the pars triangularis of the inferior frontal gyrus, and self-face-specific reduction of activation in the left middle temporal gyrus and the right supramarginal gyrus, replicating a previous finding, were not subject to such modulation. Our results thus demonstrated the recruitment of a social self during self-face recognition in the social context. At least three brain networks for self-face-specific activation may be dissociated by different patterns of response-modulation in the social context, suggesting multiple dynamic self-other representations in the human brain. Copyright © 2011 Wiley-Liss, Inc.

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

PubMed

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

2009-03-01

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

Influences of unconscious priming on voluntary actions: Role of the rostral cingulate zone.

PubMed

Teuchies, Martyn; Demanet, Jelle; Sidarus, Nura; Haggard, Patrick; Stevens, Michaël A; Brass, Marcel

2016-07-15

The ability to make voluntary, free choices is fundamental to what it means to be human. A key brain region that is involved in free choices is the rostral cingulate zone (RCZ), which is part of the medial frontal cortex. Previous research has shown that activity in this brain region can be modulated by bottom-up information while making free choices. The current study extends those findings, and shows, for the first time, that activation in the RCZ can also be modulated by subliminal information. We used a subliminal response priming paradigm to bias free and cued choices. We observed more activation in the RCZ when participants made a choice that went against the prime's suggestion, compared to when they chose according to the prime. This shows that the RCZ plays an important role in overcoming externally-triggered conflict between different response options, even when the stimuli triggering this conflict are not consciously perceived. Our results suggest that an important mechanism of endogenous action in the RCZ may therefore involve exerting an internally-generated action choice against conflicting influences, such as external sensory evidence. We further found that subliminal information also modulated activity in the anterior insula and the supramarginal gyrus. Copyright © 2016 Elsevier Inc. All rights reserved.

Loud and angry: sound intensity modulates amygdala activation to angry voices in social anxiety disorder

PubMed Central

Simon, Doerte; Becker, Michael; Mothes-Lasch, Martin; Miltner, Wolfgang H.R.

2017-01-01

Abstract Angry expressions of both voices and faces represent disorder-relevant stimuli in social anxiety disorder (SAD). Although individuals with SAD show greater amygdala activation to angry faces, previous work has failed to find comparable effects for angry voices. Here, we investigated whether voice sound-intensity, a modulator of a voice’s threat-relevance, affects brain responses to angry prosody in SAD. We used event-related functional magnetic resonance imaging to explore brain responses to voices varying in sound intensity and emotional prosody in SAD patients and healthy controls (HCs). Angry and neutral voices were presented either with normal or high sound amplitude, while participants had to decide upon the speaker’s gender. Loud vs normal voices induced greater insula activation, and angry vs neutral prosody greater orbitofrontal cortex activation in SAD as compared with HC subjects. Importantly, an interaction of sound intensity, prosody and group was found in the insula and the amygdala. In particular, the amygdala showed greater activation to loud angry voices in SAD as compared with HC subjects. This finding demonstrates a modulating role of voice sound-intensity on amygdalar hyperresponsivity to angry prosody in SAD and suggests that abnormal processing of interpersonal threat signals in amygdala extends beyond facial expressions in SAD. PMID:27651541

‘Inner voices’: the cerebral representation of emotional voice cues described in literary texts

PubMed Central

Kreifelts, Benjamin; Gößling-Arnold, Christina; Wertheimer, Jürgen; Wildgruber, Dirk

2014-01-01

While non-verbal affective voice cues are generally recognized as a crucial behavioral guide in any day-to-day conversation their role as a powerful source of information may extend well beyond close-up personal interactions and include other modes of communication such as written discourse or literature as well. Building on the assumption that similarities between the different ‘modes’ of voice cues may not only be limited to their functional role but may also include cerebral mechanisms engaged in the decoding process, the present functional magnetic resonance imaging study aimed at exploring brain responses associated with processing emotional voice signals described in literary texts. Emphasis was placed on evaluating ‘voice’ sensitive as well as task- and emotion-related modulations of brain activation frequently associated with the decoding of acoustic vocal cues. Obtained findings suggest that several similarities emerge with respect to the perception of acoustic voice signals: results identify the superior temporal, lateral and medial frontal cortex as well as the posterior cingulate cortex and cerebellum to contribute to the decoding process, with similarities to acoustic voice perception reflected in a ‘voice’-cue preference of temporal voice areas as well as an emotion-related modulation of the medial frontal cortex and a task-modulated response of the lateral frontal cortex. PMID:24396008

Activations of c-fos/c-jun signaling are involved in the modulation of hypothalamic superoxide dismutase (SOD) and neuropeptide Y (NPY) gene expression in amphetamine-mediated appetite suppression

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

Hsieh, Y.-S.; Yang, S.-F.; Chiou, H.-L.

2006-04-15

Amphetamine (AMPH) is known as an anorectic agent. The mechanism underlying the anorectic action of AMPH has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an appetite stimulant in the brain. This study was aimed to examine the molecular mechanisms behind the anorectic effect of AMPH. Results showed that AMPH treatment decreased food intake, which was correlated with changes of NPY mRNA level, but increased c-fos, c-jun and superoxide dismutase (SOD) mRNA levels in hypothalamus. To determine if c-fos or c-jun was involved in the anorectic response of AMPH, infusions of antisense oligonucleotide into the brain weremore » performed at 1 h before daily AMPH treatment in freely moving rats, and the results showed that c-fos or c-jun knockdown could block this anorectic response and restore NPY mRNA level. Moreover, c-fos or c-jun knockdown could partially block SOD mRNA level that might involve in the modulation of NPY gene expression. It was suggested that c-fos/c-jun signaling might involve in the central regulation of AMPH-mediated feeding suppression via the modulation of NPY gene expression.« less

Posttraumatic Stress Disorder: A Theoretical Model of the Hyperarousal Subtype

PubMed Central

Weston, Charles Stewart E.

2014-01-01

Posttraumatic stress disorder (PTSD) is a frequent and distressing mental disorder, about which much remains to be learned. It is a heterogeneous disorder; the hyperarousal subtype (about 70% of occurrences and simply termed PTSD in this paper) is the topic of this article, but the dissociative subtype (about 30% of occurrences and likely involving quite different brain mechanisms) is outside its scope. A theoretical model is presented that integrates neuroscience data on diverse brain regions known to be involved in PTSD, and extensive psychiatric findings on the disorder. Specifically, the amygdala is a multifunctional brain region that is crucial to PTSD, and processes peritraumatic hyperarousal on grounded cognition principles to produce hyperarousal symptoms. Amygdala activity also modulates hippocampal function, which is supported by a large body of evidence, and likewise amygdala activity modulates several brainstem regions, visual cortex, rostral anterior cingulate cortex (rACC), and medial orbitofrontal cortex (mOFC), to produce diverse startle, visual, memory, numbing, anger, and recklessness symptoms. Additional brain regions process other aspects of peritraumatic responses to produce further symptoms. These contentions are supported by neuroimaging, neuropsychological, neuroanatomical, physiological, cognitive, and behavioral evidence. Collectively, the model offers an account of how responses at the time of trauma are transformed into an extensive array of the 20 PTSD symptoms that are specified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition. It elucidates the neural mechanisms of a specific form of psychopathology, and accords with the Research Domain Criteria framework. PMID:24772094

Focused Ultrasound Immunotherapy for Central Nervous System Pathologies: Challenges and Opportunities

PubMed Central

Curley, Colleen T.; Sheybani, Natasha D.; Bullock, Timothy N.; Price, Richard J.

2017-01-01

Immunotherapy is rapidly emerging as the cornerstone for the treatment of several forms of metastatic cancer, as well as for a host of other pathologies. Meanwhile, several new high-profile studies have uncovered remarkable linkages between the central nervous and immune systems. With these recent developments, harnessing the immune system for the treatment of brain pathologies is a promising strategy. Here, we contend that MR image-guided focused ultrasound (FUS) represents a noninvasive approach that will allow for favorable therapeutic immunomodulation in the setting of the central nervous system. One obstacle to effective immunotherapeutic drug delivery to the brain is the blood brain barrier (BBB), which refers to the specialized structure of brain capillaries that prevents transport of most therapeutics from the blood into brain tissue. When applied in the presence of circulating microbubbles, FUS can safely and transiently open the BBB to facilitate the delivery of immunotherapeutic agents into the brain parenchyma. Furthermore, it has been demonstrated that physical perturbations of the tissue microenvironment via FUS can modulate immune response in both normal and diseased tissue. In this review article, we provide an overview of FUS energy regimens and corresponding tissue bioeffects, followed by a review of the literature pertaining to FUS for therapeutic antibody delivery in normal brain and preclinical models of brain disease. We provide an overview of studies that demonstrate FUS-mediated immune modulation in both the brain and peripheral settings. Finally, we provide remarks on challenges facing FUS immunotherapy and opportunities for future expansion in this area. PMID:29109764

Unveiling the Dual Role of the Dopaminergic System on Locomotion and the Innate Value for an Aversive Olfactory Stimulus in Drosophila.

PubMed

Fuenzalida-Uribe, Nicolás; Campusano, Jorge M

2018-02-10

The communication between sensory systems and the specific brain centers that process this information is crucial to develop adequate behavioral responses. Modulatory systems, including dopaminergic circuits, regulate this communication to finely tune the behavioral response associated to any given stimulus. For instance, the Mushroom Body (MB), an insect brain integration center that receives and processes several sensory stimuli and organizes the execution of motor programs, communicates with MB output neurons (MBONs) to develop behavioral responses associated to olfactory stimuli. This communication is modulated by dopaminergic neural systems. Here we show that silencing dopaminergic neurons increases the aversive response observed in adult flies exposed to Benzaldehyde (Bz) or octanol. We studied the contribution of two dopaminergic clusters that innervate different zones of MB, Protocerebral anterior medial (PAM) and Protocerebral posterior lateral 1 (PPL1), on the innate value to the aversive stimulus and the associated locomotor behavior. In order to do this, we manipulated the synaptic transmission of these neural clusters through the expression of Tetanus toxin, Kir2.1 and Transient receptor potential cation channel A1 (TrpA1) channels. Our results show that neurons in PPL1 and PAM differentially modulate the innate value to Bz in adult flies. On the other hand, blocking neurotransmission or genetic silencing of PAM neurons results in decreased locomotor behavior in flies, an effect not observed when silencing PPL1. Our results suggest that as in mammals, specific dopaminergic pathways differentially modulate locomotor behavior and the innate value for an odorant, a limbic-like response in Drosophila. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Cholinergic and serotonergic modulation of visual information processing in monkey V1.

PubMed

Shimegi, Satoshi; Kimura, Akihiro; Sato, Akinori; Aoyama, Chisa; Mizuyama, Ryo; Tsunoda, Keisuke; Ueda, Fuyuki; Araki, Sera; Goya, Ryoma; Sato, Hiromichi

2016-09-01

The brain dynamically changes its input-output relationship depending on the behavioral state and context in order to optimize information processing. At the molecular level, cholinergic/monoaminergic transmitters have been extensively studied as key players for the state/context-dependent modulation of brain function. In this paper, we review how cortical visual information processing in the primary visual cortex (V1) of macaque monkey, which has a highly differentiated laminar structure, is optimized by serotonergic and cholinergic systems by examining anatomical and in vivo electrophysiological aspects to highlight their similarities and distinctions. We show that these two systems have a similar layer bias for axonal fiber innervation and receptor distribution. The common target sites are the geniculorecipient layers and geniculocortical fibers, where the appropriate gain control is established through a geniculocortical signal transformation. Both systems exert activity-dependent response gain control across layers, but in a manner consistent with the receptor subtype. The serotonergic receptors 5-HT1B and 5HT2A modulate the contrast-response curve in a manner consistent with bi-directional response gain control, where the sign (facilitation/suppression) is switched according to the firing rate and is complementary to the other. On the other hand, cholinergic nicotinic/muscarinic receptors exert mono-directional response gain control without a sign reversal. Nicotinic receptors increase the response magnitude in a multiplicative manner, while muscarinic receptors exert both suppressive and facilitative effects. We discuss the implications of the two neuromodulator systems in hierarchical visual signal processing in V1 on the basis of the developed laminar structure. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Astrocytes require insulin-like growth factor I to protect neurons against oxidative injury

PubMed Central

Genis, Laura; Dávila, David; Fernandez, Silvia; Pozo-Rodrigálvarez, Andrea; Martínez-Murillo, Ricardo; Torres-Aleman, Ignacio

2014-01-01

Oxidative stress is a proposed mechanism in brain aging, making the study of its regulatory processes an important aspect of current neurobiological research. In this regard, the role of the aging regulator insulin-like growth factor I (IGF-I) in brain responses to oxidative stress remains elusive as both beneficial and detrimental actions have been ascribed to this growth factor. Because astrocytes protect neurons against oxidative injury, we explored whether IGF-I participates in astrocyte neuroprotection and found that blockade of the IGF-I receptor in astrocytes abrogated their rescuing effect on neurons. We found that IGF-I directly protects astrocytes against oxidative stress (H 2O 2). Indeed, in astrocytes but not in neurons, IGF-I decreases the pro-oxidant protein thioredoxin-interacting protein 1 and normalizes the levels of reactive oxygen species. Furthermore, IGF-I cooperates with trophic signals produced by astrocytes in response to H 2O 2 such as stem cell factor (SCF) to protect neurons against oxidative insult. After stroke, a condition associated with brain aging where oxidative injury affects peri-infarcted regions, a simultaneous increase in SCF and IGF-I expression was found in the cortex, suggesting that a similar cooperative response takes place in vivo. Cell-specific modulation by IGF-I of brain responses to oxidative stress may contribute in clarifying the role of IGF-I in brain aging. PMID:24715976

Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation

NASA Astrophysics Data System (ADS)

Nguyen, T. A. K.; DiGiovanna, J.; Cavuscens, S.; Ranieri, M.; Guinand, N.; van de Berg, R.; Carpaneto, J.; Kingma, H.; Guyot, J.-P.; Micera, S.; Perez Fornos, A.

2016-08-01

Objective. The vestibular system provides essential information about balance and spatial orientation via the brain to other sensory and motor systems. Bilateral vestibular loss significantly reduces quality of life, but vestibular implants (VIs) have demonstrated potential to restore lost function. However, optimal electrical stimulation strategies have not yet been identified in patients. In this study, we compared the two most common strategies, pulse amplitude modulation (PAM) and pulse rate modulation (PRM), in patients. Approach. Four subjects with a modified cochlear implant including electrodes targeting the peripheral vestibular nerve branches were tested. Charge-equivalent PAM and PRM were applied after adaptation to baseline stimulation. Vestibulo-ocular reflex eye movement responses were recorded to evaluate stimulation efficacy during acute clinical testing sessions. Main results. PAM evoked larger amplitude eye movement responses than PRM. Eye movement response axes for lateral canal stimulation were marginally better aligned with PRM than with PAM. A neural network model was developed for the tested stimulation strategies to provide insights on possible neural mechanisms. This model suggested that PAM would consistently cause a larger ensemble firing rate of neurons and thus larger responses than PRM. Significance. Due to the larger magnitude of eye movement responses, our findings strongly suggest PAM as the preferred strategy for initial VI modulation.

High-Definition Transcranial Direct Current Stimulation Enhances Conditioned Pain Modulation in Healthy Volunteers: A Randomized Trial.

PubMed

Flood, Andrew; Waddington, Gordon; Cathcart, Stuart

2016-05-01

Transcranial direct current stimulation (tDCS) is a form of brain stimulation that allows for the selective increase or decrease in the cortical excitability of a targeted region. When applied over the motor cortex it has been shown to induce changes in cortical and subcortical brain regions involved in descending pain inhibition or conditioned pain modulation (CPM). The aim of the current study was to assess whether activation of pain inhibitory pathways via tDCS of the motor cortex facilitates the CPM response. Elevated CPM after active tDCS of the motor cortex was hypothesized. Thirty healthy male volunteers attended 2 experimental sessions separated by 7 days. Both sessions consisted of CPM assessment after 20 minutes of either active or sham (placebo) tDCS over the motor cortex. CPM capacity was assessed via the pain-inhibits-pain protocol; CPM responses were shown to be elevated after active compared with sham tDCS. This report concludes that tDCS of the motor cortex enhances the CPM response in healthy men. This finding supports the potential utility of tDCS interventions in clinical pain treatment. The use of noninvasive brain stimulation over the motor cortex was shown to enhance the CPM effect. This finding supports the use of tDCS in the treatment of chronic pain, particularly in sufferers exhibiting maladaptive CPM. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Effect of menstrual cycle phase on corticolimbic brain activation by visual food cues.

PubMed

Frank, Tamar C; Kim, Ginah L; Krzemien, Alicja; Van Vugt, Dean A

2010-12-02

Food intake is decreased during the late follicular phase and increased in the luteal phase of the menstrual cycle. While a changing ovarian steroid milieu is believed to be responsible for this behavior, the specific mechanisms involved are poorly understood. Brain activity in response to visual food stimuli was compared during the estrogen dominant peri-ovulatory phase and the progesterone dominant luteal phase of the menstrual cycle. Twelve women underwent functional magnetic resonance imaging during the peri-ovulatory and luteal phases of the menstrual cycle in a counterbalanced fashion. Whole brain T2* images were collected while subjects viewed pictures of high calorie (HC) foods, low calorie (LC) foods, and control (C) pictures presented in a block design. Blood oxygen level dependent (BOLD) signal in the late follicular phase and luteal phase was determined for the contrasts HC-C, LC-C, HC-LC, and LC-HC. Both HC and LC stimuli activated numerous corticolimbic brain regions in the follicular phase, whereas only HC stimuli were effective in the luteal phase. Activation of the nucleus accumbens (NAc), amygdala, and hippocampus in response to the HC-C contrast and the hippocampus in response to the LC-C contrast was significantly increased in the late follicular phase compared to the luteal phase. Activation of the orbitofrontal cortex and mid cingulum in response to the HC-LC contrast was greater during the luteal phase. These results demonstrate for the first time that brain responses to visual food cues are influenced by menstrual cycle phase. We postulate that ovarian steroid modulation of the corticolimbic brain contributes to changes in ingestive behavior during the menstrual cycle. Copyright © 2010 Elsevier B.V. All rights reserved.

Chronic Ethanol Exposure Produces Time- and Brain Region-Dependent Changes in Gene Coexpression Networks

PubMed Central

Osterndorff-Kahanek, Elizabeth A.; Becker, Howard C.; Lopez, Marcelo F.; Farris, Sean P.; Tiwari, Gayatri R.; Nunez, Yury O.; Harris, R. Adron; Mayfield, R. Dayne

2015-01-01

Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY), nucleus accumbens (NAC), prefrontal cortex (PFC), and liver after four weekly cycles of chronic intermittent ethanol (CIE) vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000) at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600). Within each region, there was little gene overlap across time (~20%). All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global ‘rewiring‘ of coexpression systems involving glial and immune signaling as well as neuronal genes. PMID:25803291

A pilot study of a novel therapeutic approach to obesity: CNS modification by N.I.R. H.E.G. neurofeedback.

PubMed

Percik, Ruth; Cina, Jenny; Even, Batel; Gitler, Asaf; Geva, Diklah; Seluk, Lior; Livny, Abigail

2018-02-07

Despite the thorough mapping of brain pathways involved in eating behavior, no treatment aimed at modulating eating dysregulation from its neurocognitive root has been established yet. We aimed to evaluate the effect of N.I.R. H.E.G. (Near Infra-Red Hemoencephalography) neurofeedback training on appetite control, weight and food-related brain activity. Six healthy male participants with overweight or mild obesity went through 10 N.I.R. H.E.G. neurofeedback sessions designed to practice voluntary activation of the prefrontal cortex. Weight, eating behavior, appetite control and brain activity related to food and self-inhibition based on fMRI were evaluated before and after neurofeedback training. Our study group demonstrated a positive trend of increased self-control and inhibition related to food behavior, reduced weight and increased activation during an fMRI response-inhibition task (Go-No-Go - GNG) in the predefined region of interest (ROI): superior orbitofrontal cortex (sOFC). N.I.R. H.E.G. holds a promising potential as a feasible neurofeedback platform for modulation of cortical brain circuits involved in self-control and eating behavior and should be further evaluated and developed as a brain modifying device for the treatment and prevention of obesity. Copyright © 2018. Published by Elsevier Ltd.

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.

The modulation of EEG variability between internally- and externally-driven cognitive states varies with maturation and task performance

PubMed Central

Willatt, Stephanie E.; Cortese, Filomeno; Protzner, Andrea B.

2017-01-01

Increasing evidence suggests that brain signal variability is an important measure of brain function reflecting information processing capacity and functional integrity. In this study, we examined how maturation from childhood to adulthood affects the magnitude and spatial extent of state-to-state transitions in brain signal variability, and how this relates to cognitive performance. We looked at variability changes between resting-state and task (a symbol-matching task with three levels of difficulty), and within trial (fixation, post-stimulus, and post-response). We calculated variability with multiscale entropy (MSE), and additionally examined spectral power density (SPD) from electroencephalography (EEG) in children aged 8–14, and in adults aged 18–33. Our results suggest that maturation is characterized by increased local information processing (higher MSE at fine temporal scales) and decreased long-range interactions with other neural populations (lower MSE at coarse temporal scales). Children show MSE changes that are similar in magnitude, but greater in spatial extent when transitioning between internally- and externally-driven brain states. Additionally, we found that in children, greater changes in task difficulty were associated with greater magnitude of modulation in MSE. Our results suggest that the interplay between maturational and state-to-state changes in brain signal variability manifest across different spatial and temporal scales, and influence information processing capacity in the brain. PMID:28750035

Empathic brain responses in insula are modulated by levels of alexithymia but not autism.

PubMed

Bird, Geoffrey; Silani, Giorgia; Brindley, Rachel; White, Sarah; Frith, Uta; Singer, Tania

2010-05-01

Difficulties in social cognition are well recognized in individuals with autism spectrum conditions (henceforth 'autism'). Here we focus on one crucial aspect of social cognition: the ability to empathize with the feelings of another. In contrast to theory of mind, a capacity that has often been observed to be impaired in individuals with autism, much less is known about the capacity of individuals with autism for affect sharing. Based on previous data suggesting that empathy deficits in autism are a function of interoceptive deficits related to alexithymia, we aimed to investigate empathic brain responses in autistic and control participants with high and low degrees of alexithymia. Using functional magnetic resonance imaging, we measured empathic brain responses with an 'empathy for pain' paradigm assessing empathic brain responses in a real-life social setting that does not rely on attention to, or recognition of, facial affect cues. Confirming previous findings, empathic brain responses to the suffering of others were associated with increased activation in left anterior insula and the strength of this signal was predictive of the degree of alexithymia in both autistic and control groups but did not vary as a function of group. Importantly, there was no difference in the degree of empathy between autistic and control groups after accounting for alexithymia. These findings suggest that empathy deficits observed in autism may be due to the large comorbidity between alexithymic traits and autism, rather than representing a necessary feature of the social impairments in autism.

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.

Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Aβ40 and Aβ42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats.

PubMed

Ismail, Norsharina; Ismail, Maznah; Azmi, Nur Hanisah; Bakar, Muhammad Firdaus Abu; Yida, Zhang; Abdullah, Maizaton Atmadini; Basri, Hamidon

2017-11-01

Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-β (Aβ) accumulation due to abnormal amyloid-β precursor protein (APP) processing and Aβ metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aβ metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Aβ generation; APP processing, β-secretase 1 (BACE1), γ-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Aβ degradation; insulin degrading enzyme (IDE), Aβ transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Aβ fragment length 1-40 and 1-42 (Aβ40 and Aβ42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of β- and γ-secretase enzyme activity, and the Aβ degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Aβ generation, degradation and transportation in the rat's brain tissue. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Tracking the Reorganization of Module Structure in Time-Varying Weighted Brain Functional Connectivity Networks.

PubMed

Schmidt, Christoph; Piper, Diana; Pester, Britta; Mierau, Andreas; Witte, Herbert

2018-05-01

Identification of module structure in brain functional networks is a promising way to obtain novel insights into neural information processing, as modules correspond to delineated brain regions in which interactions are strongly increased. Tracking of network modules in time-varying brain functional networks is not yet commonly considered in neuroscience despite its potential for gaining an understanding of the time evolution of functional interaction patterns and associated changing degrees of functional segregation and integration. We introduce a general computational framework for extracting consensus partitions from defined time windows in sequences of weighted directed edge-complete networks and show how the temporal reorganization of the module structure can be tracked and visualized. Part of the framework is a new approach for computing edge weight thresholds for individual networks based on multiobjective optimization of module structure quality criteria as well as an approach for matching modules across time steps. By testing our framework using synthetic network sequences and applying it to brain functional networks computed from electroencephalographic recordings of healthy subjects that were exposed to a major balance perturbation, we demonstrate the framework's potential for gaining meaningful insights into dynamic brain function in the form of evolving network modules. The precise chronology of the neural processing inferred with our framework and its interpretation helps to improve the currently incomplete understanding of the cortical contribution for the compensation of such balance perturbations.

Oxytocin And Vasopressin Modulation Of The Neural Correlates Of Motivation And Emotion: Results From Functional MRI Studies In Awake Rats

PubMed Central

Febo, Marcelo; Ferris, Craig F.

2014-01-01

Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. PMID:24486356

Social context and perceived agency affects empathy for pain: an event-related fMRI investigation.

PubMed

Akitsuki, Yuko; Decety, Jean

2009-08-15

Studying of the impact of social context on the perception of pain in others is important for understanding the role of intentionality in interpersonal sensitivity, empathy, and implicit moral reasoning. Here we used an event-related fMRI with pain and social context (i.e., the number of individuals in the stimuli) as the two factors to investigate how different social contexts and resulting perceived agency modulate the neural response to the perception of pain in others. Twenty-six healthy participants were scanned while presented with short dynamic visual stimuli depicting painful situations accidentally caused by or intentionally caused by another individual. The main effect of perception of pain was associated with signal increase in the aMCC, insula, somatosensory cortex, SMA and PAG. Importantly, perceiving the presence of another individual led to specific hemodynamic increase in regions involved in representing social interaction and emotion regulation including the temporoparietal junction, medial prefrontal cortex, inferior frontal gyrus, and orbitofrontal cortex. Furthermore, the functional connectivity pattern between the left amygdala and other brain areas was modulated by the perceived agency. Our study demonstrates that the social context in which pain occurs modulate the brain response to other's pain. This modulation may reflect successful adaptation to potential danger present in a social interaction. Our results contribute to a better understanding of the neural mechanisms underpinning implicit moral reasoning that concern actions that can harm other people.

Neural control of vascular reactions: impact of emotion and attention.

PubMed

Okon-Singer, Hadas; Mehnert, Jan; Hoyer, Jana; Hellrung, Lydia; Schaare, Herma Lina; Dukart, Juergen; Villringer, Arno

2014-03-19

This study investigated the neural regions involved in blood pressure reactions to negative stimuli and their possible modulation by attention. Twenty-four healthy human subjects (11 females; age = 24.75 ± 2.49 years) participated in an affective perceptual load task that manipulated attention to negative/neutral distractor pictures. fMRI data were collected simultaneously with continuous recording of peripheral arterial blood pressure. A parametric modulation analysis examined the impact of attention and emotion on the relation between neural activation and blood pressure reactivity during the task. When attention was available for processing the distractor pictures, negative pictures resulted in behavioral interference, neural activation in brain regions previously related to emotion, a transient decrease of blood pressure, and a positive correlation between blood pressure response and activation in a network including prefrontal and parietal regions, the amygdala, caudate, and mid-brain. These effects were modulated by attention; behavioral and neural responses to highly negative distractor pictures (compared with neutral pictures) were smaller or diminished, as was the negative blood pressure response when the central task involved high perceptual load. Furthermore, comparing high and low load revealed enhanced activation in frontoparietal regions implicated in attention control. Our results fit theories emphasizing the role of attention in the control of behavioral and neural reactions to irrelevant emotional distracting information. Our findings furthermore extend the function of attention to the control of autonomous reactions associated with negative emotions by showing altered blood pressure reactions to emotional stimuli, the latter being of potential clinical relevance.

Amygdala responses to unpleasant pictures are influenced by task demands and positive affect trait.

PubMed

Sanchez, Tiago A; Mocaiber, Izabela; Erthal, Fatima S; Joffily, Mateus; Volchan, Eliane; Pereira, Mirtes G; de Araujo, Draulio B; Oliveira, Leticia

2015-01-01

The role of attention in emotional processing is still the subject of debate. Recent studies have found that high positive affect in approach motivation narrows attention. Furthermore, the positive affect trait has been suggested as an important component for determining human variability in threat reactivity. We employed functional magnetic resonance imaging to investigate whether different states of attention control would modulate amygdala responses to highly unpleasant pictures relative to neutral and whether this modulation would be influenced by the positive affect trait. Participants (n = 22, 12 male) were scanned while viewing neutral (people) or unpleasant pictures (mutilated bodies) flanked by two peripheral bars. They were instructed to (a) judge the picture content as unpleasant or neutral or (b) to judge the difference in orientation between the bars in an easy condition (0 or 90(∘) orientation difference) or (c) in a hard condition (0 or 6(∘) orientation difference). Whole brain analysis revealed a task main effect of brain areas related to the experimental manipulation of attentional control, including the amygdala, dorsolateral prefrontal cortex, and posterior parietal cortex. Region of interest analysis showed an inverse correlation (r = -0.51, p < 0.01) between left amygdala activation and positive affect level when participants viewed unpleasant stimuli and judged bar orientation in the easy condition. This result suggests that subjects with high positive affect exhibit lower amygdala reactivity to distracting unpleasant pictures. In conclusion, the current study suggests that positive affect modulates attention effect on unpleasant pictures, therefore attenuating emotional responses.

Modulation of electric brain responses evoked by pitch deviants through transcranial direct current stimulation.

PubMed

Royal, Isabelle; Zendel, Benjamin Rich; Desjardins, Marie-Ève; Robitaille, Nicolas; Peretz, Isabelle

2018-01-31

Congenital amusia is a neurodevelopmental disorder, characterized by a difficulty detecting pitch deviation that is related to abnormal electrical brain responses. Abnormalities found along the right fronto-temporal pathway between the inferior frontal gyrus (IFG) and the auditory cortex (AC) are the likely neural mechanism responsible for amusia. To investigate the causal role of these regions during the detection of pitch deviants, we applied cathodal (inhibitory) transcranial direct current stimulation (tDCS) over right frontal and right temporal regions during separate testing sessions. We recorded participants' electrical brain activity (EEG) before and after tDCS stimulation while they performed a pitch change detection task. Relative to a sham condition, there was a decrease in P3 amplitude after cathodal stimulation over both frontal and temporal regions compared to pre-stimulation baseline. This decrease was associated with small pitch deviations (6.25 cents), but not large pitch deviations (200 cents). Overall, this demonstrates that using tDCS to disrupt regions around the IFG and AC can induce temporary changes in evoked brain activity when processing pitch deviants. These electrophysiological changes are similar to those observed in amusia and provide causal support for the connection between P3 and fronto-temporal brain regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2013-01-01

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

Reward-based hypertension control by a synthetic brain-dopamine interface.

PubMed

Rössger, Katrin; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

2013-11-05

Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study.

PubMed

Lee, Katrina; Lenards, Nishele; Holson, Janice

2016-01-01

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient׳s neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient׳s data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

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.

Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders.

PubMed

Jęśko, Henryk; Wencel, Przemysław; Strosznajder, Robert P; Strosznajder, Joanna B

2017-03-01

Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD + levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD + -dependent post-translational protein modifiers. The cross-talk between SIRTs TFs and PARPs is a highly promising research target in a number of brain pathologies. This review describes updated results on sirtuins in brain aging/neurodegeneration. It focuses on SIRT1 but also on the roles of mitochondrial SIRTs (SIRT3, 4, 5) and on SIRT6 and SIRT2 localized in the nucleus and in cytosol, respectively. The involvement of SIRTs in regulation of insulin-like growth factor signaling in the brain during aging and in Alzheimer's disease was also focused. Moreover, we analyze the mechanism(s) and potential significance of interactions between SIRTs and several TFs in the regulation of cell survival and death. A critical view is given on the application of SIRT activators/modulators in therapy of neurodegenerative diseases.

Regional GABA Concentrations Modulate Inter-network Resting-state Functional Connectivity.

PubMed

Chen, Xi; Fan, Xiaoying; Hu, Yuzheng; Zuo, Chun; Whitfield-Gabrieli, Susan; Holt, Daphne; Gong, Qiyong; Yang, Yihong; Pizzagalli, Diego A; Du, Fei; Ongur, Dost

2018-03-28

Coordinated activity within and differential activity between large-scale neuronal networks such as the default mode network (DMN) and the control network (CN) is a critical feature of brain organization. The CN usually exhibits activations in response to cognitive tasks while the DMN shows deactivations; in addition, activity between the two networks is anti-correlated at rest. To address this issue, we used functional MRI to measure whole-brain BOLD signal during resting-state and task-evoked conditions, and MR spectroscopy (MRS) to quantify GABA and glutamate concentrations, in nodes within the DMN and CN (MPFC and DLPFC, respectively) in 19 healthy individuals at 3 Tesla. We found that GABA concentrations in the MPFC were significantly associated with DMN deactivation during a working memory task and with anti-correlation between DMN and CN at rest and during task performance, while GABA concentrations in the DLPFC weakly modulated DMN-CN anti-correlation in the opposite direction. Highlighting specificity, glutamate played a less significant role related to brain activity. These findings indicate that GABA in the MPFC is potentially involved in orchestrating between-network brain activity at rest and during task performance.

Clarifying the Ghrelin System’s Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand

PubMed Central

Edwards, Alexander; Abizaid, Alfonso

2017-01-01

Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor (GHSR), a receptor found in relatively high concentrations in hypothalamic and mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can be explained by the effects of this hormone on regions of the brain that have a more permeable blood brain barrier (BBB), ghrelin produced within the periphery demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are expressed. Therefore, one of the most pressing unanswered questions plaguing ghrelin research is how GHSRs, distributed in brain regions protected by the BBB, are activated despite ghrelin’s predominant peripheral production and poor ability to transverse the BBB. This manuscript will describe how peripheral ghrelin activates central GHSRs to encourage feeding, and how central ghrelin synthesis and ghrelin independent activation of GHSRs may also contribute to the modulation of feeding behaviours. PMID:28422060

Neural correlates of preparatory and regulatory control over positive and negative emotion.

PubMed

Seo, Dongju; Olman, Cheryl A; Haut, Kristen M; Sinha, Rajita; MacDonald, Angus W; Patrick, Christopher J

2014-04-01

This study used functional magnetic resonance imaging to investigate brain activation during preparatory and regulatory control while participants (N = 24) were instructed either to simply view or decrease their emotional response to, pleasant, neutral or unpleasant pictures. A main effect of emotional valence on brain activity was found in the right precentral gyrus, with greater activation during positive than negative emotion regulation. A main effect of regulation phase was evident in the bilateral anterior prefrontal cortex (PFC), precuneus, posterior cingulate cortex, right putamen and temporal and occipital lobes, with greater activity in these regions during preparatory than regulatory control. A valence X regulation interaction was evident in regions of ventromedial PFC and anterior cingulate cortex, reflecting greater activation while regulating negative than positive emotion, but only during active emotion regulation (not preparation). Conjunction analyses revealed common brain regions involved in differing types of emotion regulation including selected areas of left lateral PFC, inferior parietal lobe, temporal lobe, right cerebellum and bilateral dorsomedial PFC. The right lateral PFC was additionally activated during the modulation of both positive and negative valence. Findings demonstrate significant modulation of brain activity during both preparation for, and active regulation of positive and negative emotional states.

Brain processes in women and men in response to emotive sounds.

PubMed

Rigo, Paola; De Pisapia, Nicola; Bornstein, Marc H; Putnick, Diane L; Serra, Mauro; Esposito, Gianluca; Venuti, Paola

2017-04-01

Adult appropriate responding to salient infant signals is vital to child healthy psychological development. Here we investigated how infant crying, relative to other emotive sounds of infant laughing or adult crying, captures adults' brain resources. In a sample of nulliparous women and men, we investigated the effects of different sounds on cerebral activation of the default mode network (DMN) and reaction times (RTs) while listeners engaged in self-referential decision and syllabic counting tasks, which, respectively, require the activation or deactivation of the DMN. Sounds affect women and men differently. In women, infant crying deactivated the DMN during the self-referential decision task; in men, female adult crying interfered with the DMN during the syllabic counting task. These findings point to different brain processes underlying responsiveness to crying in women and men and show that cerebral activation is modulated by situational contexts in which crying occurs.

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

Consequences of Traumatic Brain Injury for Human Vergence Dynamics

PubMed Central

Tyler, Christopher W.; Likova, Lora T.; Mineff, Kristyo N.; Elsaid, Anas M.; Nicholas, Spero C.

2015-01-01

Purpose: Traumatic brain injury involving loss of consciousness has focal effects in the human brainstem, suggesting that it may have particular consequences for eye movement control. This hypothesis was investigated by measurements of vergence eye movement parameters. Methods: Disparity vergence eye movements were measured for a population of 123 normally sighted individuals, 26 of whom had suffered diffuse traumatic brain injury (dTBI) in the past, while the remainder served as controls. Vergence tracking responses were measured to sinusoidal disparity modulation of a random-dot field. Disparity vergence step responses were characterized in terms of their dynamic parameters separately for the convergence and divergence directions. Results: The control group showed notable differences between convergence and divergence dynamics. The dTBI group showed significantly abnormal vergence behavior on many of the dynamic parameters. Conclusion: The results support the hypothesis that occult injury to the oculomotor control system is a common residual outcome of dTBI. PMID:25691880

Modulation of auditory processing during speech movement planning is limited in adults who stutter

PubMed Central

Daliri, Ayoub; Max, Ludo

2015-01-01

Stuttering is associated with atypical structural and functional connectivity in sensorimotor brain areas, in particular premotor, motor, and auditory regions. It remains unknown, however, which specific mechanisms of speech planning and execution are affected by these neurological abnormalities. To investigate pre-movement sensory modulation, we recorded 12 stuttering and 12 nonstuttering adults’ auditory evoked potentials in response to probe tones presented prior to speech onset in a delayed-response speaking condition vs. no-speaking control conditions (silent reading; seeing nonlinguistic symbols). Findings indicate that, during speech movement planning, the nonstuttering group showed a statistically significant modulation of auditory processing (reduced N1 amplitude) that was not observed in the stuttering group. Thus, the obtained results provide electrophysiological evidence in support of the hypothesis that stuttering is associated with deficiencies in modulating the cortical auditory system during speech movement planning. This specific sensorimotor integration deficiency may contribute to inefficient feedback monitoring and, consequently, speech dysfluencies. PMID:25796060

Persistency and flexibility of complex brain networks underlie dual-task interference.

PubMed

Alavash, Mohsen; Hilgetag, Claus C; Thiel, Christiane M; Gießing, Carsten

2015-09-01

Previous studies on multitasking suggest that performance decline during concurrent task processing arises from interfering brain modules. Here, we used graph-theoretical network analysis to define functional brain modules and relate the modular organization of complex brain networks to behavioral dual-task costs. Based on resting-state and task fMRI we explored two organizational aspects potentially associated with behavioral interference when human subjects performed a visuospatial and speech task simultaneously: the topological overlap between persistent single-task modules, and the flexibility of single-task modules in adaptation to the dual-task condition. Participants showed a significant decline in visuospatial accuracy in the dual-task compared with single visuospatial task. Global analysis of topological similarity between modules revealed that the overlap between single-task modules significantly correlated with the decline in visuospatial accuracy. Subjects with larger overlap between single-task modules showed higher behavioral interference. Furthermore, lower flexible reconfiguration of single-task modules in adaptation to the dual-task condition significantly correlated with larger decline in visuospatial accuracy. Subjects with lower modular flexibility showed higher behavioral interference. At the regional level, higher overlap between single-task modules and less modular flexibility in the somatomotor cortex positively correlated with the decline in visuospatial accuracy. Additionally, higher modular flexibility in cingulate and frontal control areas and lower flexibility in right-lateralized nodes comprising the middle occipital and superior temporal gyri supported dual-tasking. Our results suggest that persistency and flexibility of brain modules are important determinants of dual-task costs. We conclude that efficient dual-tasking benefits from a specific balance between flexibility and rigidity of functional brain modules. © 2015 Wiley Periodicals, Inc.

Phosphatidyl-Inositol-3 Kinase Inhibitors Regulate Peptidoglycan-Induced Myeloid Leukocyte Recruitment, Inflammation, and Neurotoxicity in Mouse Brain.

PubMed

Arroyo, Daniela S; Gaviglio, Emilia A; Peralta Ramos, Javier M; Bussi, Claudio; Avalos, Maria P; Cancela, Liliana M; Iribarren, Pablo

2018-01-01

Acute brain injury leads to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral myeloid cells (MC), which contribute to the inflammatory response involved in neuronal damage. We previously reported that TLR2 stimulation by peptidoglycan (PGN) from Staphylococcus aureus, in vitro and in vivo , induced microglial cell activation followed by autophagy induction. In this report, we evaluated if phosphatidyl-inositol-3 kinase (PI3K) pharmacological inhibitors LY294200 and 3-methyladenine (3-MA) can modulate the innate immune response to PGN in the central nervous system. We found that injection of PGN into the mouse brain parenchyma (caudate putamen) triggered an inflammatory reaction, which involved activation of microglial cells, recruitment of infiltrating MC to injection site, production of pro-inflammatory mediators, and neuronal injury. In addition, we observed the accumulation of LC3B + CD45 + cells and colocalization of LC3B and lysosomal-associated membrane protein 1 in brain cells. Besides, we found that pharmacological inhibitors of PI3K, including the classical autophagy inhibitor 3-MA, reduced the recruitment of MC, microglial cell activation, and neurotoxicity induced by brain PGN injection. Collectively, our results suggest that PI3K pathways and autophagic response may participate in the PGN-induced microglial activation and MC recruitment to the brain. Thus, inhibition of these pathways could be therapeutically targeted to control acute brain inflammatory conditions.

Phosphatidyl-Inositol-3 Kinase Inhibitors Regulate Peptidoglycan-Induced Myeloid Leukocyte Recruitment, Inflammation, and Neurotoxicity in Mouse Brain

PubMed Central

Arroyo, Daniela S.; Gaviglio, Emilia A.; Peralta Ramos, Javier M.; Bussi, Claudio; Avalos, Maria P.; Cancela, Liliana M.; Iribarren, Pablo

2018-01-01

Acute brain injury leads to the recruitment and activation of immune cells including resident microglia and infiltrating peripheral myeloid cells (MC), which contribute to the inflammatory response involved in neuronal damage. We previously reported that TLR2 stimulation by peptidoglycan (PGN) from Staphylococcus aureus, in vitro and in vivo, induced microglial cell activation followed by autophagy induction. In this report, we evaluated if phosphatidyl-inositol-3 kinase (PI3K) pharmacological inhibitors LY294200 and 3-methyladenine (3-MA) can modulate the innate immune response to PGN in the central nervous system. We found that injection of PGN into the mouse brain parenchyma (caudate putamen) triggered an inflammatory reaction, which involved activation of microglial cells, recruitment of infiltrating MC to injection site, production of pro-inflammatory mediators, and neuronal injury. In addition, we observed the accumulation of LC3B+ CD45+ cells and colocalization of LC3B and lysosomal-associated membrane protein 1 in brain cells. Besides, we found that pharmacological inhibitors of PI3K, including the classical autophagy inhibitor 3-MA, reduced the recruitment of MC, microglial cell activation, and neurotoxicity induced by brain PGN injection. Collectively, our results suggest that PI3K pathways and autophagic response may participate in the PGN-induced microglial activation and MC recruitment to the brain. Thus, inhibition of these pathways could be therapeutically targeted to control acute brain inflammatory conditions. PMID:29719536

Redox modulation of cellular stress response and lipoxin A4 expression by Coriolus versicolor in rat brain: Relevance to Alzheimer's disease pathogenesis.

PubMed

Trovato, A; Siracusa, R; Di Paola, R; Scuto, M; Fronte, V; Koverech, G; Luca, M; Serra, A; Toscano, M A; Petralia, A; Cuzzocrea, S; Calabrese, V

2016-03-01

Increasing evidence supports the notion that oxidative stress-driven neuroinflammation is an early pathological feature in neurodegenerative diseases. As a prominent intracellular redox system involved in neuroprotection, the vitagene system is emerging as a potential neurohormetic target for novel cytoprotective interventions. Vitagenes encode for cytoprotective heat shock proteins 70, heme oxygenase-1, thioredoxin and lipoxin A4. Emerging interest is now focusing on molecules capable of activating the vitagene system as novel therapeutic targets to minimize deleterious consequences associated with free radical-induced cell damage, such as in neurodegeneration. Mushroom-derived lipoxin A4 (LXA4) is an emerging endogenous eicosanoid able to promote resolution of inflammation, acting as an endogenous "braking signal" in the inflammatory process. Mushrooms have long been used in traditional medicine for thousands of years, being now increasingly recognized as rich source of polysaccharopeptides endowed with significant antitumor, antioxidant, antiviral, antibacterial and cytoprotective effects, thereby capable of stimulating host immune responses. Here we provide evidence of a neuroprotective action of the Coriolus mushroom when administered orally to rat. Expression of LXA4 was measured in different brain regions after oral administration of a Coriolus biomass preparation, given for 30 days. LXA4 up-regulation was associated with an increased content of redox sensitive proteins involved in cellular stress response, such as Hsp72, heme oxygenase-1 and thioredoxin. In the brain of rats receiving Coriolus, maximum induction of LXA4 was observed in cortex and hippocampus. Hsps induction was associated with no significant changes in IkBα, NFkB and COX-2 brain levels. Conceivably, activation of LXA4 signaling and modulation of stress-responsive vitagene proteins could serve as a potential therapeutic target for AD-related inflammation and neurodegenerative damage. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain dynamics in ASD during movie-watching show idiosyncratic functional integration and segregation.

PubMed

Bolton, Thomas A W; Jochaut, Delphine; Giraud, Anne-Lise; Van De Ville, Dimitri

2018-06-01

To refine our understanding of autism spectrum disorders (ASD), studies of the brain in dynamic, multimodal and ecological experimental settings are required. One way to achieve this is to compare the neural responses of ASD and typically developing (TD) individuals when viewing a naturalistic movie, but the temporal complexity of the stimulus hampers this task, and the presence of intrinsic functional connectivity (FC) may overshadow movie-driven fluctuations. Here, we detected inter-subject functional correlation (ISFC) transients to disentangle movie-induced functional changes from underlying resting-state activity while probing FC dynamically. When considering the number of significant ISFC excursions triggered by the movie across the brain, connections between remote functional modules were more heterogeneously engaged in the ASD population. Dynamically tracking the temporal profiles of those ISFC changes and tying them to specific movie subparts, this idiosyncrasy in ASD responses was then shown to involve functional integration and segregation mechanisms such as response inhibition, background suppression, or multisensory integration, while low-level visual processing was spared. Through the application of a new framework for the study of dynamic experimental paradigms, our results reveal a temporally localized idiosyncrasy in ASD responses, specific to short-lived episodes of long-range functional interplays. © 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Functional variation of the dopamine D2 receptor gene is associated with emotional control as well as brain activity and connectivity during emotion processing in humans

PubMed Central

Blasi, Giuseppe; Bianco, Luciana Lo; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Fazio, Leonardo; Papazacharias, Apostolos; Di Giorgio, Annabella; Caforio, Grazia; Rampino, Antonio; Masellis, Rita; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Bertolino, Alessandro

2010-01-01

Personality traits related to emotion processing are, at least in part, heritable and genetically determined. Dopamine D2 receptor signaling is involved in modulation of emotional behavior and activity of associated brain regions such as the amygdala and the prefrontal cortex. An intronic single nucleotide polymorphism within the D2 receptor gene (DRD2, rs1076560, guanine>thymine - G>T) shifts splicing of the two protein isoforms (D2 short, D2S, mainly presynaptic, and D2 long, D2L) and has been associated with modulation of memory performance and brain activity. Here, our aim was to investigate the association of DRD2 rs1076560 genotype with personality traits of emotional stability and with brain physiology during processing of emotionally relevant stimuli. DRD2 genotype and Big Five Questionnaire scores were evaluated in 134 healthy subjects demonstrating that GG subjects have reduced ‘emotion control’ compared with GT subjects. fMRI in a sample of 24 individuals indicated greater amygdala activity during implicit processing and greater dorsolateral prefrontal cortex (DLPFC) response during explicit processing of facial emotional stimuli in GG subjects compared with GT. Other results also demonstrate an interaction between DRD2 genotype and facial emotional expression on functional connectivity of both amygdala and dorsolateral prefrontal regions with overlapping medial prefrontal areas. Moreover, rs1076560 genotype is associated with differential relationships between amygdala/DLPFC functional connectivity and emotion control scores. These results suggest that genetically determined D2 signaling may explain part of personality traits related to emotion processing and individual variability in specific brain responses to emotionally relevant inputs. PMID:19940176

Functional variation of the dopamine D2 receptor gene is associated with emotional control as well as brain activity and connectivity during emotion processing in humans.

PubMed

Blasi, Giuseppe; Lo Bianco, Luciana; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Fazio, Leonardo; Papazacharias, Apostolos; Di Giorgio, Annabella; Caforio, Grazia; Rampino, Antonio; Masellis, Rita; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Bertolino, Alessandro

2009-11-25

Personality traits related to emotion processing are, at least in part, heritable and genetically determined. Dopamine D(2) receptor signaling is involved in modulation of emotional behavior and activity of associated brain regions such as the amygdala and the prefrontal cortex. An intronic single nucleotide polymorphism within the D(2) receptor gene (DRD2) (rs1076560, guanine > thymine or G > T) shifts splicing of the two protein isoforms (D(2) short, mainly presynaptic, and D(2) long) and has been associated with modulation of memory performance and brain activity. Here, our aim was to investigate the association of DRD2 rs1076560 genotype with personality traits of emotional stability and with brain physiology during processing of emotionally relevant stimuli. DRD2 genotype and Big Five Questionnaire scores were evaluated in 134 healthy subjects demonstrating that GG subjects have reduced "emotion control" compared with GT subjects. Functional magnetic resonance imaging in a sample of 24 individuals indicated greater amygdala activity during implicit processing and greater dorsolateral prefrontal cortex (DLPFC) response during explicit processing of facial emotional stimuli in GG subjects compared with GT. Other results also demonstrate an interaction between DRD2 genotype and facial emotional expression on functional connectivity of both amygdala and dorsolateral prefrontal regions with overlapping medial prefrontal areas. Moreover, rs1076560 genotype is associated with differential relationships between amygdala/DLPFC functional connectivity and emotion control scores. These results suggest that genetically determined D(2) signaling may explain part of personality traits related to emotion processing and individual variability in specific brain responses to emotionally relevant inputs.

Relation of visual creative imagery manipulation to resting-state brain oscillations.

PubMed

Cai, Yuxuan; Zhang, Delong; Liang, Bishan; Wang, Zengjian; Li, Junchao; Gao, Zhenni; Gao, Mengxia; Chang, Song; Jiao, Bingqing; Huang, Ruiwang; Liu, Ming

2018-02-01

Visual creative imagery (VCI) manipulation is the key component of visual creativity; however, it remains largely unclear how it occurs in the brain. The present study investigated the brain neural response to VCI manipulation and its relation to intrinsic brain activity. We collected functional magnetic resonance imaging (fMRI) datasets related to a VCI task and a control task as well as pre- and post-task resting states in sequential sessions. A general linear model (GLM) was subsequently used to assess the specific activation of the VCI task compared with the control task. The changes in brain oscillation amplitudes across the pre-, on-, and post-task states were measured to investigate the modulation of the VCI task. Furthermore, we applied a Granger causal analysis (GCA) to demonstrate the dynamic neural interactions that underlie the modulation effect. We determined that the VCI task specifically activated the left inferior frontal gyrus pars triangularis (IFGtriang) and the right superior frontal gyrus (SFG), as well as the temporoparietal areas, including the left inferior temporal gyrus, right precuneus, and bilateral superior parietal gyrus. Furthermore, the VCI task modulated the intrinsic brain activity of the right IFGtriang (0.01-0.08 Hz) and the left caudate nucleus (0.2-0.25 Hz). Importantly, an inhibitory effect (negative) may exist from the left SFG to the right IFGtriang in the on-VCI task state, in the frequency of 0.01-0.08 Hz, whereas this effect shifted to an excitatory effect (positive) in the subsequent post-task resting state. Taken together, the present findings provide experimental evidence for the existence of a common mechanism that governs the brain activity of many regions at resting state and whose neural activity may engage during the VCI manipulation task, which may facilitate an understanding of the neural substrate of visual creativity.

Cortical organization of inhibition-related functions and modulation by psychopathology

PubMed Central

Warren, Stacie L.; Crocker, Laura D.; Spielberg, Jeffery M.; Engels, Anna S.; Banich, Marie T.; Sutton, Bradley P.; Miller, Gregory A.; Heller, Wendy

2013-01-01

Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG) and worry (BA10). Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology. PMID:23781192

Cortical organization of inhibition-related functions and modulation by psychopathology.

PubMed

Warren, Stacie L; Crocker, Laura D; Spielberg, Jeffery M; Engels, Anna S; Banich, Marie T; Sutton, Bradley P; Miller, Gregory A; Heller, Wendy

2013-01-01

Individual differences in inhibition-related functions have been implicated as risk factors for a broad range of psychopathology, including anxiety and depression. Delineating neural mechanisms of distinct inhibition-related functions may clarify their role in the development and maintenance of psychopathology. The present study tested the hypothesis that activity in common and distinct brain regions would be associated with an ecologically sensitive, self-report measure of inhibition and a laboratory performance measure of prepotent response inhibition. Results indicated that sub-regions of DLPFC distinguished measures of inhibition, whereas left inferior frontal gyrus and bilateral inferior parietal cortex were associated with both types of inhibition. Additionally, co-occurring anxiety and depression modulated neural activity in select brain regions associated with response inhibition. Results imply that specific combinations of anxiety and depression dimensions are associated with failure to implement top-down attentional control as reflected in inefficient recruitment of posterior DLPFC and increased activation in regions associated with threat (MTG) and worry (BA10). Present findings elucidate possible neural mechanisms of interference that could help explain executive control deficits in psychopathology.

Oxytocin and the social brain: neural mechanisms and perspectives in human research.

PubMed

Kanat, Manuela; Heinrichs, Markus; Domes, Gregor

2014-09-11

The present paper summarizes functional imaging studies investigating the effects of intranasal oxytocin (OT) on brain responses to social stimuli. We aim to integrate previous research, point to unresolved issues and highlight perspectives for future studies. The studies so far have focused on identifying neural circuits underlying social information processing which are particularly sensitive to modulations by exogenous OT. Most consistently, stimulus-related responses of the amygdala and associated areas within the prefrontal and temporal cortices have been found to be modulated by OT administration. However, there are a number of unresolved issues related to the possible role of sex differences and hormonal status, genetic variability, and individual differences in socio-cognitive functioning. Future studies focusing on these open questions are expected to contribute to a more nuanced understanding of the role of the central OT system in humans and may provide the basis for novel treatment approaches for mental disorders characterized by social deficits. This article is part of a Special Issue entitled Oxytocin and Social Behav. © 2013 Published by Elsevier B.V.

Nature plus nurture: the triggering of multiple sclerosis.

PubMed

Wekerle, Hartmut

2015-01-01

Recent clinical and experimental studies indicate that multiple sclerosis develops as consequence of a failed interplay between genetic ("nature") and environmental ("nurture") factors. A large number of risk genes favour an autoimmune response against the body's own brain matter. New experimental data indicate that the actual trigger of this attack is however provided by an interaction of brain-specific immune cells with components of the regular commensal gut flora, the intestinal microbiota. This concept opens the way for new therapeutic approaches involving modulation of the microbiota by dietary or antibiotic regimens.

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

PubMed Central

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

2012-01-01

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

Glutamatergic stimulation of the left dentate gyrus abolishes depressive-like behaviors in a rat learned helplessness paradigm.

PubMed

Seo, Jeho; Cho, Hojin; Kim, Gun Tae; Kim, Chul Hoon; Kim, Dong Goo

2017-10-01

Episodic experiences of stress have been identified as the leading cause of major depressive disorder (MDD). The occurrence of MDD is profoundly influenced by the individual's coping strategy, rather than the severity of the stress itself. Resting brain activity has been shown to alter in several mental disorders. However, the functional relationship between resting brain activity and coping strategies has not yet been studied. In the present study, we observed different patterns of resting brain activity in rats that had determined either positive (resilient to stress) or negative (vulnerable to stress) coping strategies, and examined whether modulation of the preset resting brain activity could influence the behavioral phenotype associated with negative coping strategy (i.e., depressive-like behaviors). We used a learned helplessness paradigm-a well-established model of MDD-to detect coping strategies. Differences in resting state brain activity between animals with positive and negative coping strategies were assessed using 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET). Glutamatergic stimulation was used to modulate resting brain activity. After exposure to repeated uncontrollable stress, seven of 23 rats exhibited positive coping strategies, while eight of 23 rats exhibited negative coping strategies. Increased resting brain activity was observed only in the left ventral dentate gyrus of the positive coping rats using FDG-PET. Furthermore, glutamatergic stimulation of the left dentate gyrus abolished depressive-like behaviors in rats with negative coping strategies. Increased resting brain activity in the left ventral dentate gyrus helps animals to select positive coping strategies in response to future stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Modulation of meso-limbic reward processing by motivational tendencies in young adolescents and adults

PubMed Central

Joseph, Jane E.; Zhu, Xun; Lynam, Donald; Kelly, Thomas H.

2015-01-01

Adolescence is a particularly vulnerable period for the onset of substance use disorders and other psychopathology. Individual variability in motivational tendencies and temperament and significant changes in functional brain organization during adolescence are important factors to consider in the development of substance use and dependence. Recent conceptualizations suggest that sensitivity to reward is heightened in adolescence and that this motivation tendency may precipitate subsequent substance abuse. The present study examined the role of personality traits in mesolimbic neurobehavioral response on a monetary incentive delay (MID) task in young adolescents (11–14 years) and emerging adults (18–25 years) using functional magnetic resonance imaging. As a group, adolescents were not more sensitive to gains than losses compared to adults during either anticipatory and feedback phases; instead, compared to adults they showed less sensitivity to incentive magnitude in mesolimbic circuitry during anticipation and feedback stages. However, personality modulated this response such that adolescents high in impulsivity or low in avoidance tendencies showed greater gain sensitivity and adolescents high in avoidance showed greater loss sensitivity during cue anticipation. In adults, mesolimbic response was modulated by the impulsivity construct such that high-impulsive adults showed reduced magnitude sensitivity during both anticipation and feedback compared to low impulsive adults. The present findings suggest that impulsive personality significantly modulates mesolimbic reward response during both adolescence and adulthood but avoidance and approach tendencies also modulate this response in adolescents. Moreover, personality modulated incentive valence in adolescents but incentive magnitude in adults. Collectively, these findings suggest that mesolimbic reward circuitry function is modulated by somewhat different parameters in adolescence than in adulthood. PMID:26690806

Social cognition in members of conflict groups: behavioural and neural responses in Arabs, Israelis and South Americans to each other's misfortunes

PubMed Central

Bruneau, Emile G.; Dufour, Nicholas; Saxe, Rebecca

2012-01-01

In contexts of cultural conflict, people delegitimize the other group's perspective and lose compassion for the other group's suffering. These psychological biases have been empirically characterized in intergroup settings, but rarely in groups involved in active conflict. Similarly, the basic brain networks involved in recognizing others' narratives and misfortunes have been identified, but how these brain networks are modulated by intergroup conflict is largely untested. In the present study, we examined behavioural and neural responses in Arab, Israeli and South American participants while they considered the pain and suffering of individuals from each group. Arabs and Israelis reported feeling significantly less compassion for each other's pain and suffering (the ‘conflict outgroup’), but did not show an ingroup bias relative to South Americans (the ‘distant outgroup’). In contrast, the brain regions that respond to others' tragedies showed an ingroup bias relative to the distant outgroup but not the conflict outgroup, particularly for descriptions of emotional suffering. Over all, neural responses to conflict group members were qualitatively different from neural responses to distant group members. This is the first neuroimaging study to examine brain responses to others' suffering across both distant and conflict groups, and provides a first step towards building a foundation for the biological basis of conflict. PMID:22271787

Obesity-Induced Hypertension: Brain Signaling Pathways

PubMed Central

da Silva, Alexandre A.; Wang, Zhen; Fang, Taolin; Aberdein, Nicola; de Lara Rodriguez, Cecilia E. P.; Hall, John E.

2017-01-01

Obesity greatly increases the risk for cardiovascular, metabolic, and renal diseases and is one of the most significant and preventable causes of increased blood pressure (BP) in patients with essential hypertension. This review high-lights recent advances in our understanding of central nervous system (CNS) signaling pathways that contribute to the etiology and pathogenesis of obesity-induced hypertension. We discuss the role of excess adiposity and activation of the brain leptin-melanocortin system in causing increased sympathetic activity in obesity. In addition, we highlight other potential brain mechanisms by which increased weight gain modulates metabolic and cardiovascular functions. Unraveling the CNS mechanisms responsible for increased sympathetic activation and hypertension and how circulating hormones activate brain signaling pathways to control BP offer potentially important therapeutic targets for obesity and hypertension. PMID:27262997

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain

PubMed Central

Zhou, Tao; Hong, Guosong; Fu, Tian-Ming; Yang, Xiao; Schuhmann, Thomas G.; Viveros, Robert D.; Lieber, Charles M.

2017-01-01

Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2–12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future. PMID:28533392

Syringe-injectable mesh electronics integrate seamlessly with minimal chronic immune response in the brain.

PubMed

Zhou, Tao; Hong, Guosong; Fu, Tian-Ming; Yang, Xiao; Schuhmann, Thomas G; Viveros, Robert D; Lieber, Charles M

2017-06-06

Implantation of electrical probes into the brain has been central to both neuroscience research and biomedical applications, although conventional probes induce gliosis in surrounding tissue. We recently reported ultraflexible open mesh electronics implanted into rodent brains by syringe injection that exhibit promising chronic tissue response and recording stability. Here we report time-dependent histology studies of the mesh electronics/brain-tissue interface obtained from sections perpendicular and parallel to probe long axis, as well as studies of conventional flexible thin-film probes. Confocal fluorescence microscopy images of the perpendicular and parallel brain slices containing mesh electronics showed that the distribution of astrocytes, microglia, and neurons became uniform from 2-12 wk, whereas flexible thin-film probes yield a marked accumulation of astrocytes and microglia and decrease of neurons for the same period. Quantitative analyses of 4- and 12-wk data showed that the signals for neurons, axons, astrocytes, and microglia are nearly the same from the mesh electronics surface to the baseline far from the probes, in contrast to flexible polymer probes, which show decreases in neuron and increases in astrocyte and microglia signals. Notably, images of sagittal brain slices containing nearly the entire mesh electronics probe showed that the tissue interface was uniform and neurons and neurofilaments penetrated through the mesh by 3 mo postimplantation. The minimal immune response and seamless interface with brain tissue postimplantation achieved by ultraflexible open mesh electronics probes provide substantial advantages and could enable a wide range of opportunities for in vivo chronic recording and modulation of brain activity in the future.

Enhancing response inhibition by incentive: Comparison of adolescents with and without substance use disorder

PubMed Central

Chung, Tammy; Geier, Charles; Luna, Beatriz; Pajtek, Stefan; Terwilliger, Robert; Thatcher, Dawn; Clark, Duncan

2010-01-01

Effective response inhibition is a key component of recovery from addiction. Some research suggests that response inhibition can be enhanced through reward contingencies. We examined the effect of monetary incentive on response inhibition among adolescents with and without substance use disorder (SUD) using a fast event-related fMRI antisaccade reward task. The fMRI task permits investigation of how reward (monetary incentive) might modulate inhibitory control during three task phases: cue presentation (reward or neutral trial), response preparation, and response execution. Adolescents with lifetime SUD (n=12; 100% marijuana use disorder) were gender and age-matched to healthy controls (n=12). Monetary incentive facilitated inhibitory control for SUD adolescents; for healthy controls, the difference in error rate for neutral and reward trials was not significant. There were no significant differences in behavioral performance between groups across reward and neutral trials, however, group differences in regional brain activation were identified. During the response preparation phase of reward trials, SUD adolescents, compared to controls, showed increased activation of prefrontal and oculomotor control (e.g., frontal eye field) areas, brain regions that have been associated with effective response inhibition. Results indicate differences in brain activation between SUD and control youth when preparing to inhibit a prepotent response in the context of reward, and support a possible role for incentives in enhancing response inhibition among youth with SUD. PMID:21115229

Lighting up the brain's reward circuitry.

PubMed

Lobo, Mary Kay

2012-07-01

The brain's reward circuit is critical for mediating natural reward behaviors including food, sex, and social interaction. Drugs of abuse take over this circuit and produce persistent molecular and cellular alterations in the brain regions and their neural circuitry that make up the reward pathway. Recent use of optogenetic technologies has provided novel insights into the functional and molecular role of the circuitry and cell subtypes within these circuits that constitute this pathway. This perspective will address the current and future use of light-activated proteins, including those involved in modulating neuronal activity, cellular signaling, and molecular properties in the neural circuitry mediating rewarding stimuli and maladaptive responses to drugs of abuse. © 2012 New York Academy of Sciences.

A Dialogue between the Immune System and Brain, Spoken in the Language of Serotonin

PubMed Central

2012-01-01

Neuropsychiatric disorders have long been linked to both immune system activation and alterations in serotonin (5-HT) signaling. In the CNS, the contributions of 5-HT modulate a broad range of targets, most notably, hypothalamic, limbic and cortical circuits linked to the control of mood and mood disorders. In the periphery, many are aware of the production and actions of 5-HT in the gut but are unaware that the molecule and its receptors are also present in the immune system where evidence suggests they contribute to the both innate and adaptive responses. In addition, there is clear evidence that the immune system communicates to the brain via both humoral and neuronal mechanisms, and that CNS 5-HT neurons are a direct or indirect target for these actions. Following a brief primer on the immune system, we describe our current understanding of the synthesis, release, and actions of 5-HT in modulating immune function, including the expression of 5-HT biosynthetic enzymes, receptors, and transporters that are typically studied with respect to the roles in the CNS. We then orient our presentation to recent findings that pro-inflammatory cytokines can modulate CNS 5-HT signaling, leading to a conceptualization that among the many roles of 5-HT in the body is an integrated physiological and behavioral response to inflammatory events and pathogens. From this perspective, altered 5-HT/immune conversations are likely to contribute to risk for neurobehavioral disorders historically linked to compromised 5-HT function or ameliorated by 5-HT targeted medications, including depression and anxiety disorders, obsessive-compulsive disorder (OCD), and autism. Our review raises the question as to whether genetic variation impacting 5-HT signaling genes may contribute to maladaptive behavior as much through perturbed immune system modulation as through altered brain mechanisms. Conversely, targeting the immune system for therapeutic development may provide an important opportunity to treat mental illness. PMID:23336044

Gender-related differences in irritable bowel syndrome: Potential mechanisms of sex hormones

PubMed Central

Meleine, Mathieu; Matricon, Julien

2014-01-01

According to epidemiological studies, twice as many women as men are affected by irritable bowel syndrome (IBS) in western countries, suggesting a role for sex hormones in IBS pathophysiology. Despite growing evidence about the implications of sex hormones in IBS symptom modulation, data on mechanisms by which they influence disease development are sparse. This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, sex, gender, ovarian hormone, estradiol, progesterone, testosterone, symptoms, pain, sensitivity, motility, permeability, stress, immune system, brain activity, spinal, supraspinal, imaging. Ovarian hormones variations along the menstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations. They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception. These hormones can also modulate the susceptibility to stress, which is a pivotal factor in IBS occurrence and symptom severity. For instance, estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function. In conclusion, whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS, they arguably modulate IBS onset and symptomatology. However, our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender. Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS. Finally, investigation of brain-gut interactions is critical to decipher how stress, ovarian hormones, and female brain processing of pain can translate into gut dysfunctions. PMID:24944465

Gender-related differences in irritable bowel syndrome: potential mechanisms of sex hormones.

PubMed

Meleine, Mathieu; Matricon, Julien

2014-06-14

According to epidemiological studies, twice as many women as men are affected by irritable bowel syndrome (IBS) in western countries, suggesting a role for sex hormones in IBS pathophysiology. Despite growing evidence about the implications of sex hormones in IBS symptom modulation, data on mechanisms by which they influence disease development are sparse. This review aims to determine the state of knowledge about the role of sex hormones in sensorimotor dysfunctions and to address the possible interplay of sex hormones with common risk factors associated with IBS. The scientific bibliography was searched using the following keywords: irritable bowel syndrome, sex, gender, ovarian hormone, estradiol, progesterone, testosterone, symptoms, pain, sensitivity, motility, permeability, stress, immune system, brain activity, spinal, supraspinal, imaging. Ovarian hormones variations along the menstrual cycle affect sensorimotor gastrointestinal function in both healthy and IBS populations. They can modulate pain processing by interacting with neuromodulator systems and the emotional system responsible for visceral pain perception. These hormones can also modulate the susceptibility to stress, which is a pivotal factor in IBS occurrence and symptom severity. For instance, estrogen-dependent hyper-responsiveness to stress can promote immune activation or impairments of gut barrier function. In conclusion, whereas it is important to keep in mind that ovarian hormones cannot be considered as a causal factor of IBS, they arguably modulate IBS onset and symptomatology. However, our understanding of the underlying mechanisms remains limited and studies assessing the link between IBS symptoms and ovarian hormone levels are needed to improve our knowledge of the disease evolution with regard to gender. Further studies assessing the role of male hormones are also needed to understand fully the role of sex hormones in IBS. Finally, investigation of brain-gut interactions is critical to decipher how stress, ovarian hormones, and female brain processing of pain can translate into gut dysfunctions.

Modulation of Gut Microbiota-Brain Axis by Probiotics, Prebiotics, and Diet.

PubMed

Liu, Xiaofei; Cao, Shangqing; Zhang, Xuewu

2015-09-16

There exists a bidirectional communication system between the gastrointestinal tract and the brain. Increasing evidence shows that gut microbiota can play a critical role in this communication; thus, the concept of a gut microbiota and brain axis is emerging. Here, we review recent findings in the relationship between intestinal microbes and brain function, such as anxiety, depression, stress, autism, learning, and memory. We highlight the advances in modulating brain development and behavior by probiotics, prebiotics, and diet through the gut microbiota-brain axis. A variety of mechanisms including immune, neural, and metabolic pathways may be involved in modulation of the gut microbiota-brain axis. We also discuss some future challenges. A deeper understanding of the relationship between the gut bacteria and their hosts is implicated in developing microbial-based therapeutic strategies for brain disorders.

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

PubMed

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

2014-08-01

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

Effects of emotion regulation strategy on brain responses to the valence and social content of visual scenes.

PubMed

Vrtička, Pascal; Sander, David; Vuilleumier, Patrik

2011-04-01

Emotion Regulation (ER) includes different mechanisms aiming at volitionally modulating emotional responses, including cognitive re-evaluation (re-appraisal; REAP) or inhibition of emotion expression and behavior (expressive suppression; ESUP). However, despite the importance of these ER strategies, previous functional magnetic resonance imaging (fMRI) studies have not sufficiently disentangled the specific neural impact of REAP versus ESUP on brain responses to different kinds of emotion-eliciting events. Moreover, although different effects have been reported for stimulus valence (positive vs. negative), no study has systematically investigated how ER may change emotional processing as a function of particular stimulus content variables (i.e., social vs. nonsocial). Our fMRI study directly compared brain activation to visual scenes during the use of different ER strategies, relative to a "natural" viewing condition, but also examined the effects of ER as a function of the social versus nonsocial content of scenes, in addition to their negative versus positive valence (by manipulating these factors orthogonally in a 2×2 factorial design). Our data revealed that several prefrontal cortical areas were differentially recruited during either REAP or ESUP, independent of the valence and content of images. In addition, selective modulations by either REAP or ESUP were found depending on the negative valence of scenes (medial fusiform gyrus, anterior insula, dmPFC), and on their nonsocial (middle insula) or social (bilateral amygdala, mPFC, posterior cingulate) significance. Furthermore, we observed a significant lateralization in the amygdala for the effect of the two different ER strategies, with a predominant modulation by REAP on the left side but by ESUP on the right side. Taken together, these results do not only highlight the distributed nature of neural changes induced by ER, but also reveal the specific impact of different strategies (REAP or ESUP), and the specific sites implicated by different dimensions of emotional information (social or negative). Copyright © 2011 Elsevier Ltd. All rights reserved.

Closed Loop Deep Brain Stimulation for PTSD, Addiction, and Disorders of Affective Facial Interpretation: Review and Discussion of Potential Biomarkers and Stimulation Paradigms

PubMed Central

Bina, Robert W.; Langevin, Jean-Phillipe

2018-01-01

The treatment of psychiatric diseases with Deep Brain Stimulation (DBS) is becoming more of a reality as studies proliferate the indications and targets for therapies. Opinions on the initial failures of DBS trials for some psychiatric diseases point to a certain lack of finesse in using an Open Loop DBS (OLDBS) system in these dynamic, cyclical pathologies. OLDBS delivers monomorphic input into dysfunctional brain circuits with modulation of that input via human interface at discrete time points with no interim modulation or adaptation to the changing circuit dynamics. Closed Loop DBS (CLDBS) promises dynamic, intrinsic circuit modulation based on individual physiologic biomarkers of dysfunction. Discussed here are several psychiatric diseases which may be amenable to CLDBS paradigms as the neurophysiologic dysfunction is stochastic and not static. Post-Traumatic Stress Disorder (PTSD) has several peripheral and central physiologic and neurologic changes preceding stereotyped hyper-activation behavioral responses. Biomarkers for CLDBS potentially include skin conductance changes indicating changes in the sympathetic nervous system, changes in serum and central neurotransmitter concentrations, and limbic circuit activation. Chemical dependency and addiction have been demonstrated to be improved with both ablation and DBS of the Nucleus Accumbens and as a serendipitous side effect of movement disorder treatment. Potential peripheral biomarkers are similar to those proposed for PTSD with possible use of environmental and geolocation based cues, peripheral signs of physiologic arousal, and individual changes in central circuit patterns. Non-substance addiction disorders have also been serendipitously treated in patients with OLDBS for movement disorders. As more is learned about these behavioral addictions, DBS targets and effectors will be identified. Finally, discussed is the use of facial recognition software to modulate activation of inappropriate responses for psychiatric diseases in which misinterpretation of social cues feature prominently. These include Autism Spectrum Disorder, PTSD, and Schizophrenia—all of which have a common feature of dysfunctional interpretation of facial affective clues. Technological advances and improvements in circuit-based, individual-specific, real-time adaptable modulation, forecast functional neurosurgery treatments for heretofore treatment-resistant behavioral diseases. PMID:29780303

Lack of NG2 exacerbates neurological outcome and modulates glial responses after traumatic brain injury.

PubMed

Huang, Changsheng; Sakry, Dominik; Menzel, Lutz; Dangel, Larissa; Sebastiani, Anne; Krämer, Tobias; Karram, Khalad; Engelhard, Kristin; Trotter, Jacqueline; Schäfer, Michael K E

2016-04-01

Traumatic brain injury (TBI) is a major cause of death and disability. The underlying pathophysiology is characterized by secondary processes including neuronal death and gliosis. To elucidate the role of the NG2 proteoglycan we investigated the response of NG2-knockout mice (NG2-KO) to TBI. Seven days after TBI behavioral analysis, brain damage volumetry and assessment of blood brain barrier integrity demonstrated an exacerbated response of NG2-KO compared to wild-type (WT) mice. Reactive astrocytes and expression of the reactive astrocyte and neurotoxicity marker Lcn2 (Lipocalin-2) were increased in the perilesional brain tissue of NG2-KO mice. In addition, microglia/macrophages with activated morphology were increased in number and mRNA expression of the M2 marker Arg1 (Arginase 1) was enhanced in NG2-KO mice. While TBI-induced expression of pro-inflammatory cytokine genes was unchanged between genotypes, PCR array screening revealed a marked TBI-induced up-regulation of the C-X-C motif chemokine 13 gene Cxcl13 in NG2-KO mice. CXCL13, known to attract immune cells to the inflamed brain, was expressed by activated perilesional microglia/macrophages seven days after TBI. Thirty days after TBI, NG2-KO mice still exhibited more pronounced neurological deficits than WT mice, up-regulation of Cxcl13, enhanced CD45+ leukocyte infiltration and a relative increase of activated Iba-1+/CD45+ microglia/macrophages. Our study demonstrates that lack of NG2 exacerbates the neurological outcome after TBI and associates with abnormal activation of astrocytes, microglia/macrophages and increased leukocyte recruitment to the injured brain. These findings suggest that NG2 may counteract neurological deficits and adverse glial responses in TBI. © 2015 Wiley Periodicals, Inc.

Immune dysregulation and cognitive vulnerability in the aging brain: Interactions of microglia, IL-1β, BDNF and synaptic plasticity.

PubMed

Patterson, Susan L

2015-09-01

Older individuals often experience declines in cognitive function after events (e.g. infection, or injury) that trigger activation of the immune system. This occurs at least in part because aging sensitizes the response of microglia (the brain's resident immune cells) to signals triggered by an immune challenge. In the aging brain, microglia respond to these signals by producing more pro-inflammatory cytokines (e.g. interleukin-1beta or IL-1β) and producing them for longer than microglia in younger brains. This exaggerated inflammatory response can compromise processes critical for optimal cognitive functioning. Interleukin-1β is central to the inflammatory response and is a key mediator and modulator of an array of associated biological functions; thus its production and release is usually very tightly regulated. This review will focus on the impact of dysregulated production of IL-1β on hippocampus dependent-memory systems and associated synaptic plasticity processes. The neurotrophin brain-derived neurotrophic factor (BNDF) helps to protect neurons from damage caused by infection or injury, and it plays a critical role in many of the same memory and hippocampal plasticity processes compromised by dysregulated production of IL-1β. This suggests that an exaggerated brain inflammatory response, arising from aging and a secondary immune challenge, may erode the capacity to provide the BDNF needed for memory-related plasticity processes at hippocampal synapses. This article is part of a Special Issue entitled 'Neuroimmunology and Synaptic Function'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pain perception and hypnosis: findings from recent functional neuroimaging studies.

PubMed

Del Casale, Antonio; Ferracuti, Stefano; Rapinesi, Chiara; Serata, Daniele; Caltagirone, Saverio Simone; Savoja, Valeria; Piacentino, Daria; Callovini, Gemma; Manfredi, Giovanni; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

2015-01-01

Hypnosis modulates pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. By reviewing functional neuroimaging studies focusing on pain perception under hypnosis, the authors aimed to identify brain activation-deactivation patterns occurring in hypnosis-modulated pain conditions. Different changes in brain functionality occurred throughout all components of the pain network and other brain areas. The anterior cingulate cortex appears to be central in modulating pain circuitry activity under hypnosis. Most studies also showed that the neural functions of the prefrontal, insular, and somatosensory cortices are consistently modified during hypnosis-modulated pain conditions. Functional neuroimaging studies support the clinical use of hypnosis in the management of pain conditions.

Vagally mediated effects of brain stem dopamine on gastric tone and phasic contractions of the rat.

PubMed

Anselmi, L; Toti, L; Bove, C; Travagli, R A

2017-11-01

Dopamine (DA)-containing fibers and neurons are embedded within the brain stem dorsal vagal complex (DVC); we have shown previously that DA modulates the membrane properties of neurons of the dorsal motor nucleus of the vagus (DMV) via DA1 and DA2 receptors. The vagally dependent modulation of gastric tone and phasic contractions, i.e., motility, by DA, however, has not been characterized. With the use of microinjections of DA in the DVC while recording gastric tone and motility, the aims of the present study were 1 ) assess the gastric effects of brain stem DA application, 2 ) identify the DA receptor subtype, and, 3 ) identify the postganglionic pathway(s) activated. Dopamine microinjection in the DVC decreased gastric tone and motility in both corpus and antrum in 29 of 34 rats, and the effects were abolished by ipsilateral vagotomy and fourth ventricular treatment with the selective DA2 receptor antagonist L741,626 but not by application of the selective DA1 receptor antagonist SCH 23390. Systemic administration of the cholinergic antagonist atropine attenuated the inhibition of corpus and antrum tone in response to DA microinjection in the DVC. Conversely, systemic administration of the nitric oxide synthase inhibitor nitro-l-arginine methyl ester did not alter the DA-induced decrease in gastric tone and motility. Our data provide evidence of a dopaminergic modulation of a brain stem vagal neurocircuit that controls gastric tone and motility. NEW & NOTEWORTHY Dopamine administration in the brain stem decreases gastric tone and phasic contractions. The gastric effects of dopamine are mediated via dopamine 2 receptors on neurons of the dorsal motor nucleus of the vagus. The inhibitory effects of dopamine are mediated via inhibition of the postganglionic cholinergic pathway. Copyright © 2017 the American Physiological Society.

Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats.

PubMed

Febo, Marcelo; Ferris, Craig F

2014-09-11

Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

Increased Global Interaction Across Functional Brain Modules During Cognitive Emotion Regulation.

PubMed

Brandl, Felix; Mulej Bratec, Satja; Xie, Xiyao; Wohlschläger, Afra M; Riedl, Valentin; Meng, Chun; Sorg, Christian

2017-07-13

Cognitive emotion regulation (CER) enables humans to flexibly modulate their emotions. While local theories of CER neurobiology suggest interactions between specialized local brain circuits underlying CER, e.g., in subparts of amygdala and medial prefrontal cortices (mPFC), global theories hypothesize global interaction increases among larger functional brain modules comprising local circuits. We tested the global CER hypothesis using graph-based whole-brain network analysis of functional MRI data during aversive emotional processing with and without CER. During CER, global between-module interaction across stable functional network modules increased. Global interaction increase was particularly driven by subregions of amygdala and cuneus-nodes of highest nodal participation-that overlapped with CER-specific local activations, and by mPFC and posterior cingulate as relevant connector hubs. Results provide evidence for the global nature of human CER, complementing functional specialization of embedded local brain circuits during successful CER. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

PubMed

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

2016-01-01

Chanting and praying are among the most popular religious activities, which are said to be able to alleviate people's negative emotions. However, the neural mechanisms underlying this mental exercise and its temporal course have hardly been investigated. Here, we used event-related potentials (ERPs) to explore the effects of chanting the name of a Buddha (Amitābha) on the brain's response to viewing negative pictures that were fear- and stress-provoking. We recorded and analyzed electroencephalography (EEG) data from 21 Buddhists with chanting experience as they viewed negative and neutral pictures. Participants were instructed to chant the names of Amitābha or Santa Claus silently to themselves or simply remain silent (no-chanting condition) during picture viewing. To measure the physiological changes corresponding to negative emotions, electrocardiogram and galvanic skin response data were also collected. Results showed that viewing negative pictures (vs. neutral pictures) increased the amplitude of the N1 component in all the chanting conditions. The amplitude of late positive potential (LPP) also increased when the negative pictures were viewed under the no-chanting and the Santa Claus condition. However, increased LPP was not observed when chanting Amitābha. The ERP source analysis confirmed this finding and showed that increased LPP mainly originated from the central-parietal regions of the brain. In addition, the participants' heart rates decreased significantly when viewing negative pictures in the Santa Claus condition. The no-chanting condition had a similar decreasing trend although not significant. However, while chanting Amitābha and viewing negative pictures participants' heart rate did not differ significantly from that observed during neutral picture viewing. It is possible that the chanting of Amitābha might have helped the participants to develop a religious schema and neutralized the effect of the negative stimuli. These findings echo similar research findings on Christian religious practices and brain responses to negative stimuli. Hence, prayer/religious practices may have cross-cultural universality in emotion regulation. This study shows for the first time that Buddhist chanting, or in a broader sense, repetition of religious prayers will not modulate brain responses to negative stimuli during the early perceptual stage, but only during the late-stage emotional/cognitive processing.

Olfactory modulation by dopamine in the context of aversive learning

PubMed Central

Riffell, Jeffrey A.; Martin, Joshua P.; Gage, Stephanie L.; Nighorn, Alan J.

2012-01-01

The need to detect and process sensory cues varies in different behavioral contexts. Plasticity in sensory coding can be achieved by the context-specific release of neuromodulators in restricted brain areas. The context of aversion triggers the release of dopamine in the insect brain, yet the effects of dopamine on sensory coding are unknown. In this study, we characterize the morphology of dopaminergic neurons that innervate each of the antennal lobes (ALs; the first synaptic neuropils of the olfactory system) of the moth Manduca sexta and demonstrate with electrophysiology that dopamine enhances odor-evoked responses of the majority of AL neurons while reducing the responses of a small minority. Because dopamine release in higher brain areas mediates aversive learning we developed a naturalistic, ecologically inspired aversive learning paradigm in which an innately appetitive host plant floral odor is paired with a mimic of the aversive nectar of herbivorized host plants. This pairing resulted in a decrease in feeding behavior that was blocked when dopamine receptor antagonists were injected directly into the ALs. These results suggest that a transient dopaminergic enhancement of sensory output from the AL contributes to the formation of aversive memories. We propose a model of olfactory modulation in which specific contexts trigger the release of different neuromodulators in the AL to increase olfactory output to downstream areas of processing. PMID:22552185

Attention and prediction in human audition: a lesson from cognitive psychophysiology

PubMed Central

Schröger, Erich; Marzecová, Anna; SanMiguel, Iria

2015-01-01

Attention is a hypothetical mechanism in the service of perception that facilitates the processing of relevant information and inhibits the processing of irrelevant information. Prediction is a hypothetical mechanism in the service of perception that considers prior information when interpreting the sensorial input. Although both (attention and prediction) aid perception, they are rarely considered together. Auditory attention typically yields enhanced brain activity, whereas auditory prediction often results in attenuated brain responses. However, when strongly predicted sounds are omitted, brain responses to silence resemble those elicited by sounds. Studies jointly investigating attention and prediction revealed that these different mechanisms may interact, e.g. attention may magnify the processing differences between predicted and unpredicted sounds. Following the predictive coding theory, we suggest that prediction relates to predictions sent down from predictive models housed in higher levels of the processing hierarchy to lower levels and attention refers to gain modulation of the prediction error signal sent up to the higher level. As predictions encode contents and confidence in the sensory data, and as gain can be modulated by the intention of the listener and by the predictability of the input, various possibilities for interactions between attention and prediction can be unfolded. From this perspective, the traditional distinction between bottom-up/exogenous and top-down/endogenous driven attention can be revisited and the classic concepts of attentional gain and attentional trace can be integrated. PMID:25728182

Explicit authenticity and stimulus features interact to modulate BOLD response induced by emotional speech.

PubMed

Drolet, Matthis; Schubotz, Ricarda I; Fischer, Julia

2013-06-01

Context has been found to have a profound effect on the recognition of social stimuli and correlated brain activation. The present study was designed to determine whether knowledge about emotional authenticity influences emotion recognition expressed through speech intonation. Participants classified emotionally expressive speech in an fMRI experimental design as sad, happy, angry, or fearful. For some trials, stimuli were cued as either authentic or play-acted in order to manipulate participant top-down belief about authenticity, and these labels were presented both congruently and incongruently to the emotional authenticity of the stimulus. Contrasting authentic versus play-acted stimuli during uncued trials indicated that play-acted stimuli spontaneously up-regulate activity in the auditory cortex and regions associated with emotional speech processing. In addition, a clear interaction effect of cue and stimulus authenticity showed up-regulation in the posterior superior temporal sulcus and the anterior cingulate cortex, indicating that cueing had an impact on the perception of authenticity. In particular, when a cue indicating an authentic stimulus was followed by a play-acted stimulus, additional activation occurred in the temporoparietal junction, probably pointing to increased load on perspective taking in such trials. While actual authenticity has a significant impact on brain activation, individual belief about stimulus authenticity can additionally modulate the brain response to differences in emotionally expressive speech.

The Emerging Role of Epigenetics in Stroke

PubMed Central

Qureshi, Irfan A.; Mehler, Mark F.

2013-01-01

The transplantation of exogenous stem cells and the activation of endogenous neural stem and progenitor cells (NSPCs) are promising treatments for stroke. These cells can modulate intrinsic responses to ischemic injury and may even integrate directly into damaged neural networks. However, the neuroprotective and neural regenerative effects that can be mediated by these cells are limited and may even be deleterious. Epigenetic reprogramming represents a novel strategy for enhancing the intrinsic potential of the brain to protect and repair itself by modulating pathologic neural gene expression and promoting the recapitulation of seminal neural developmental processes. In fact, recent evidence suggests that emerging epigenetic mechanisms are critical for orchestrating nearly every aspect of neural development and homeostasis, including brain patterning, neural stem cell maintenance, neurogenesis and gliogenesis, neural subtype specification, and synaptic and neural network connectivity and plasticity. In this review, we survey the therapeutic potential of exogenous stem cells and endogenous NSPCs and highlight innovative technological approaches for designing, developing, and delivering epigenetic therapies for targeted reprogramming of endogenous pools of NSPCs, neural cells at risk, and dysfunctional neural networks to rescue and restore neurologic function in the ischemic brain. PMID:21403016

Optimizing cholinergic tone through lynx modulators of nicotinic receptors: implications for plasticity and nicotine addiction.

PubMed

Miwa, Julie M; Lester, Henry A; Walz, Andreas

2012-08-01

The cholinergic system underlies both adaptive (learning and memory) and nonadaptive (addiction and dependency) behavioral changes through its ability to shape and regulate plasticity. Protein modulators such as lynx family members can fine tune the activity of the cholinergic system and contribute to the graded response of the cholinergic system, stabilizing neural circuitry through direct interaction with nicotinic receptors. Release of this molecular brake can unmask cholinergic-dependent mechanisms in the brain. Lynx proteins have the potential to provide top-down control over plasticity mechanisms, including addictive propensity. If this is indeed the case, then, what regulates the regulator? Transcriptional changes of lynx genes in response to pharmacological, physiological, and pathological alterations are explored in this review.

Ageing diminishes the modulation of human brain responses to visual food cues by meal ingestion.

PubMed

Cheah, Y S; Lee, S; Ashoor, G; Nathan, Y; Reed, L J; Zelaya, F O; Brammer, M J; Amiel, S A

2014-09-01

Rates of obesity are greatest in middle age. Obesity is associated with altered activity of brain networks sensing food-related stimuli and internal signals of energy balance, which modulate eating behaviour. The impact of healthy mid-life ageing on these processes has not been characterised. We therefore aimed to investigate changes in brain responses to food cues, and the modulatory effect of meal ingestion on such evoked neural activity, from young adulthood to middle age. Twenty-four healthy, right-handed subjects, aged 19.5-52.6 years, were studied on separate days after an overnight fast, randomly receiving 50 ml water or 554 kcal mixed meal before functional brain magnetic resonance imaging while viewing visual food cues. Across the group, meal ingestion reduced food cue-evoked activity of amygdala, putamen, insula and thalamus, and increased activity in precuneus and bilateral parietal cortex. Corrected for body mass index, ageing was associated with decreasing food cue-evoked activation of right dorsolateral prefrontal cortex (DLPFC) and precuneus, and increasing activation of left ventrolateral prefrontal cortex (VLPFC), bilateral temporal lobe and posterior cingulate in the fasted state. Ageing was also positively associated with the difference in food cue-evoked activation between fed and fasted states in the right DLPFC, bilateral amygdala and striatum, and negatively associated with that of the left orbitofrontal cortex and VLPFC, superior frontal gyrus, left middle and temporal gyri, posterior cingulate and precuneus. There was an overall tendency towards decreasing modulatory effects of prior meal ingestion on food cue-evoked regional brain activity with increasing age. Healthy ageing to middle age is associated with diminishing sensitivity to meal ingestion of visual food cue-evoked activity in brain regions that represent the salience of food and direct food-associated behaviour. Reduced satiety sensing may have a role in the greater risk of obesity in middle age.

The power of using functional fMRI on small rodents to study brain pharmacology and disease

PubMed Central

Jonckers, Elisabeth; Shah, Disha; Hamaide, Julie; Verhoye, Marleen; Van der Linden, Annemie

2015-01-01

Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge. The first part of this review describes the physiological basis of BOLD fMRI and the hemodynamic response on which the MRI contrast is based. Specific emphasis goes to possible effects of anesthesia and the animal’s physiological conditions on neural activity and the hemodynamic response. The second part of this review describes applications of the aforementioned techniques in pharmacologically induced, as well as in traumatic and transgenic disease models and illustrates how multiple fMRI methods can be applied successfully to evaluate different aspects of a specific disorder. For example, fMRI techniques can be used to pinpoint the neural substrate of a disease beyond previously defined hypothesis-driven regions-of-interest. In addition, fMRI techniques allow one to dissect how specific modifications (e.g., treatment, lesion etc.) modulate the functioning of specific brain areas (st-fMRI, phMRI) and how functional connectivity (rsfMRI) between several brain regions is affected, both in acute and extended time frames. Furthermore, fMRI techniques can be used to assess/explore the efficacy of novel treatments in depth, both in fundamental research as well as in preclinical settings. In conclusion, by describing several exemplary studies, we aim to highlight the advantages of functional MRI in exploring the acute and long-term effects of pharmacological substances and/or pathology on brain functioning along with several methodological considerations. PMID:26539115

Dysbindin modulates brain function during visual processing in children.

PubMed

Mechelli, A; Viding, E; Kumar, A; Pettersson-Yeo, W; Fusar-Poli, P; Tognin, S; O'Donovan, M C; McGuire, P

2010-01-01

Schizophrenia is a neurodevelopmental disorder, and risk genes are thought to act through disruption of brain development. Several genetic studies have identified dystrobrevin binding protein 1 (DTNBP1, also known as dysbindin) as a potential susceptibility gene for schizophrenia, but its impact on brain function is poorly understood. It has been proposed that DTNBP1 may be associated with differences in visual processing. To test this, we examined the impact on visual processing in 61 healthy children aged 10-12 years of a genetic variant in DTNBP1 (rs2619538) that was common to all schizophrenia associated haplotypes in an earlier UK-Irish study. We tested the hypothesis that carriers of the risk allele would show altered occipital cortical function relative to noncarriers. Functional Magnetic Resonance Imaging (fMRI) was used to measure brain responses during a visual matching task. The data were analysed using statistical parametric mapping and statistical inferences were made at p<0.05 (corrected for multiple comparisons). Relative to noncarriers, carriers of the risk allele had greater activation in the lingual, fusiform gyrus and inferior occipital gyri. In these regions DTNBP1 genotype accounted for 19%, 20% and 14% of the inter-individual variance, respectively. Our results suggest that that genetic variation in DTNBP1 is associated with differences in the function of brain areas that mediate visual processing, and that these effects are evident in young children. These findings are consistent with the notion that the DTNBP1 gene influences brain development and can thereby modulate vulnerability to schizophrenia.

The coupling of cerebral blood flow and oxygen metabolism with brain activation is similar for simple and complex stimuli in human primary visual cortex.

PubMed

Griffeth, Valerie E M; Simon, Aaron B; Buxton, Richard B

2015-01-01

Quantitative functional MRI (fMRI) experiments to measure blood flow and oxygen metabolism coupling in the brain typically rely on simple repetitive stimuli. Here we compared such stimuli with a more naturalistic stimulus. Previous work on the primary visual cortex showed that direct attentional modulation evokes a blood flow (CBF) response with a relatively large oxygen metabolism (CMRO2) response in comparison to an unattended stimulus, which evokes a much smaller metabolic response relative to the flow response. We hypothesized that a similar effect would be associated with a more engaging stimulus, and tested this by measuring the primary human visual cortex response to two contrast levels of a radial flickering checkerboard in comparison to the response to free viewing of brief movie clips. We did not find a significant difference in the blood flow-metabolism coupling (n=%ΔCBF/%ΔCMRO2) between the movie stimulus and the flickering checkerboards employing two different analysis methods: a standard analysis using the Davis model and a new analysis using a heuristic model dependent only on measured quantities. This finding suggests that in the primary visual cortex a naturalistic stimulus (in comparison to a simple repetitive stimulus) is either not sufficient to provoke a change in flow-metabolism coupling by attentional modulation as hypothesized, that the experimental design disrupted the cognitive processes underlying the response to a more natural stimulus, or that the technique used is not sensitive enough to detect a small difference. Copyright © 2014 Elsevier Inc. All rights reserved.

Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1.

PubMed

Seillier, Lenka; Lorenz, Corinna; Kawaguchi, Katsuhisa; Ott, Torben; Nieder, Andreas; Pourriahi, Paria; Nienborg, Hendrikje

2017-11-22

Serotonin, an important neuromodulator in the brain, is implicated in affective and cognitive functions. However, its role even for basic cortical processes is controversial. For example, in the mammalian primary visual cortex (V1), heterogenous serotonergic modulation has been observed in anesthetized animals. Here, we combined extracellular single-unit recordings with iontophoresis in awake animals. We examined the role of serotonin on well-defined tuning properties (orientation, spatial frequency, contrast, and size) in V1 of two male macaque monkeys. We find that in the awake macaque the modulatory effect of serotonin is surprisingly uniform: it causes a mainly multiplicative decrease of the visual responses and a slight increase in the stimulus-selective response latency. Moreover, serotonin neither systematically changes the selectivity or variability of the response, nor the interneuronal correlation unexplained by the stimulus ("noise-correlation"). The modulation by serotonin has qualitative similarities with that for a decrease in stimulus contrast, but differs quantitatively from decreasing contrast. It can be captured by a simple additive change to a threshold-linear spiking nonlinearity. Together, our results show that serotonin is well suited to control the response gain of neurons in V1 depending on the animal's behavioral or motivational context, complementing other known state-dependent gain-control mechanisms. SIGNIFICANCE STATEMENT Serotonin is an important neuromodulator in the brain and a major target for drugs used to treat psychiatric disorders. Nonetheless, surprisingly little is known about how it shapes information processing in sensory areas. Here we examined the serotonergic modulation of visual processing in the primary visual cortex of awake behaving macaque monkeys. We found that serotonin mainly decreased the gain of the visual responses, without systematically changing their selectivity, variability, or covariability. This identifies a simple computational function of serotonin for state-dependent sensory processing, depending on the animal's affective or motivational state. Copyright © 2017 Seillier, Lorenz et al.

Serotonin Decreases the Gain of Visual Responses in Awake Macaque V1

PubMed Central

Seillier, Lenka; Lorenz, Corinna; Kawaguchi, Katsuhisa; Ott, Torben; Pourriahi, Paria

2017-01-01

Serotonin, an important neuromodulator in the brain, is implicated in affective and cognitive functions. However, its role even for basic cortical processes is controversial. For example, in the mammalian primary visual cortex (V1), heterogenous serotonergic modulation has been observed in anesthetized animals. Here, we combined extracellular single-unit recordings with iontophoresis in awake animals. We examined the role of serotonin on well-defined tuning properties (orientation, spatial frequency, contrast, and size) in V1 of two male macaque monkeys. We find that in the awake macaque the modulatory effect of serotonin is surprisingly uniform: it causes a mainly multiplicative decrease of the visual responses and a slight increase in the stimulus-selective response latency. Moreover, serotonin neither systematically changes the selectivity or variability of the response, nor the interneuronal correlation unexplained by the stimulus (“noise-correlation”). The modulation by serotonin has qualitative similarities with that for a decrease in stimulus contrast, but differs quantitatively from decreasing contrast. It can be captured by a simple additive change to a threshold-linear spiking nonlinearity. Together, our results show that serotonin is well suited to control the response gain of neurons in V1 depending on the animal's behavioral or motivational context, complementing other known state-dependent gain-control mechanisms. SIGNIFICANCE STATEMENT Serotonin is an important neuromodulator in the brain and a major target for drugs used to treat psychiatric disorders. Nonetheless, surprisingly little is known about how it shapes information processing in sensory areas. Here we examined the serotonergic modulation of visual processing in the primary visual cortex of awake behaving macaque monkeys. We found that serotonin mainly decreased the gain of the visual responses, without systematically changing their selectivity, variability, or covariability. This identifies a simple computational function of serotonin for state-dependent sensory processing, depending on the animal's affective or motivational state. PMID:29042433

Arginine Vasopressin Effects on Subjective Judgments and Neural Responses to Same and Other-Sex Faces in Men and Women.

PubMed

Rilling, James K; Li, Ting; Chen, Xiangchuan; Gautam, Pritam; Haroon, Ebrahim; Thompson, Richmond R

2017-01-01

Arginine vasopressin (AVP) influences social and emotional behaviors across a wide range of species. In humans, intranasal AVP has been previously shown to alter physiological responses to and subjective judgments of same-sex faces in both men and women. The present study attempted to elucidate the neural mechanism for these effects by randomizing 40 healthy men and 40 healthy women to treatment with either 40 IU intranasal AVP or a saline placebo approximately 30 min before imaging their brain function with fMRI as they viewed same and other-sex faces. All subjects were also scanned a second time several days later with no treatment to evaluate the persistence of AVP effects over time. AVP acutely increased positive ratings of same-sex faces in women, with some evidence that these effects persisted until the second scan. While AVP had no acute effects on same-sex ratings in men, AVP increased positive ratings of same-sex faces several days later. On the other hand, AVP had no effect on other-sex face judgments in either sex. AVP modulation of brain function was focused on the nucleus accumbens (NAc) and the lateral septum, two reward processing areas involved in the formation of social bonds. AVP provoked acute increases in right NAc and bilateral lateral septum responses to female faces among men, with left lateral septum responses persisting over time while right NAc responses reversed over time. Finally, AVP modulated hypothalamic activation to faces in both men and women. The present study therefore indicates that intranasal AVP affects subjective ratings and neural responses to same and other-sex faces in men and women, with some effects persisting and others emerging over time. Future studies should investigate whether AVP effects are modulated by individual variables such as genotype, personality, or attachment style as previously reported for other nonapeptides.

Endogenous dopamine (DA) modulates (3H)spiperone binding in vivo in rat brain

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

Bischoff, S.; Krauss, J.; Grunenwald, C.

1991-01-01

(3H)spiperone (SPI) binding in vivo, biochemical parameters and behavior were measured after modulating DA levels by various drug treatments. DA releasers and uptake inhibitors increased SPI binding in rat striatum. In other brain areas, the effects were variable, but only the pituitary remained unaffected. Surprisingly, nomifensine decreased SPI binding in frontal cortex. The effects of these drugs were monitored by measuring DA, serotonin (5-HT) and their metabolites in the same rats. The increased SPI binding in striatum was parallel to the locomotor stimulation with the following rank order: amfonelic acid greater than nomifensine greater than D-amphetamine greater than or equalmore » to methylphenidate greater than amineptine greater than bupropion. Decreasing DA levels with reserpine or alpha-methyl-para-tyrosine reduced SPI binding by 45% in striatum only when both drugs were combined. In contrast, reserpine enhanced SPI binding in pituitary. Thus, the amount of releasable DA seems to modulate SPI binding characteristics. It is suggested that in vivo, DA receptors are submitted to dynamic regulation in response to changes in intrasynaptic concentrations of DA.« less

Thoughts of Death Modulate Psychophysical and Cortical Responses to Threatening Stimuli

PubMed Central

Valentini, Elia; Koch, Katharina; Aglioti, Salvatore Maria

2014-01-01

Existential social psychology studies show that awareness of one's eventual death profoundly influences human cognition and behaviour by inducing defensive reactions against end-of-life related anxiety. Much less is known about the impact of reminders of mortality on brain activity. Therefore we explored whether reminders of mortality influence subjective ratings of intensity and threat of auditory and painful thermal stimuli and the associated electroencephalographic activity. Moreover, we explored whether personality and demographics modulate psychophysical and neural changes related to mortality salience (MS). Following MS induction, a specific increase in ratings of intensity and threat was found for both nociceptive and auditory stimuli. While MS did not have any specific effect on nociceptive and auditory evoked potentials, larger amplitude of theta oscillatory activity related to thermal nociceptive activity was found after thoughts of death were induced. MS thus exerted a top-down modulation on theta electroencephalographic oscillatory amplitude, specifically for brain activity triggered by painful thermal stimuli. This effect was higher in participants reporting higher threat perception, suggesting that inducing a death-related mind-set may have an influence on body-defence related somatosensory representations. PMID:25386905

Neural correlates of word production stages delineated by parametric modulation of psycholinguistic variables.

PubMed

Wilson, Stephen M; Isenberg, Anna Lisette; Hickok, Gregory

2009-11-01

Word production is a complex multistage process linking conceptual representations, lexical entries, phonological forms and articulation. Previous studies have revealed a network of predominantly left-lateralized brain regions supporting this process, but many details regarding the precise functions of different nodes in this network remain unclear. To better delineate the functions of regions involved in word production, we used event-related functional magnetic resonance imaging (fMRI) to identify brain areas where blood oxygen level-dependent (BOLD) responses to overt picture naming were modulated by three psycholinguistic variables: concept familiarity, word frequency, and word length, and one behavioral variable: reaction time. Each of these variables has been suggested by prior studies to be associated with different aspects of word production. Processing of less familiar concepts was associated with greater BOLD responses in bilateral occipitotemporal regions, reflecting visual processing and conceptual preparation. Lower frequency words produced greater BOLD signal in left inferior temporal cortex and the left temporoparietal junction, suggesting involvement of these regions in lexical selection and retrieval and encoding of phonological codes. Word length was positively correlated with signal intensity in Heschl's gyrus bilaterally, extending into the mid-superior temporal gyrus (STG) and sulcus (STS) in the left hemisphere. The left mid-STS site was also modulated by reaction time, suggesting a role in the storage of lexical phonological codes.

Loud and angry: sound intensity modulates amygdala activation to angry voices in social anxiety disorder.

PubMed

Simon, Doerte; Becker, Michael; Mothes-Lasch, Martin; Miltner, Wolfgang H R; Straube, Thomas

2017-03-01

Angry expressions of both voices and faces represent disorder-relevant stimuli in social anxiety disorder (SAD). Although individuals with SAD show greater amygdala activation to angry faces, previous work has failed to find comparable effects for angry voices. Here, we investigated whether voice sound-intensity, a modulator of a voice's threat-relevance, affects brain responses to angry prosody in SAD. We used event-related functional magnetic resonance imaging to explore brain responses to voices varying in sound intensity and emotional prosody in SAD patients and healthy controls (HCs). Angry and neutral voices were presented either with normal or high sound amplitude, while participants had to decide upon the speaker's gender. Loud vs normal voices induced greater insula activation, and angry vs neutral prosody greater orbitofrontal cortex activation in SAD as compared with HC subjects. Importantly, an interaction of sound intensity, prosody and group was found in the insula and the amygdala. In particular, the amygdala showed greater activation to loud angry voices in SAD as compared with HC subjects. This finding demonstrates a modulating role of voice sound-intensity on amygdalar hyperresponsivity to angry prosody in SAD and suggests that abnormal processing of interpersonal threat signals in amygdala extends beyond facial expressions in SAD. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Experimental and theoretical characterization of the voltage distribution generated by deep brain stimulation.

PubMed

Miocinovic, Svjetlana; Lempka, Scott F; Russo, Gary S; Maks, Christopher B; Butson, Christopher R; Sakaie, Ken E; Vitek, Jerrold L; McIntyre, Cameron C

2009-03-01

Deep brain stimulation (DBS) is an established therapy for the treatment of Parkinson's disease and shows great promise for numerous other disorders. While the fundamental purpose of DBS is to modulate neural activity with electric fields, little is known about the actual voltage distribution generated in the brain by DBS electrodes and as a result it is difficult to accurately predict which brain areas are directly affected by the stimulation. The goal of this study was to characterize the spatial and temporal characteristics of the voltage distribution generated by DBS electrodes. We experimentally recorded voltages around active DBS electrodes in either a saline bath or implanted in the brain of a non-human primate. Recordings were made during voltage-controlled and current-controlled stimulation. The experimental findings were compared to volume conductor electric field models of DBS parameterized to match the different experiments. Three factors directly affected the experimental and theoretical voltage measurements: 1) DBS electrode impedance, primarily dictated by a voltage drop at the electrode-electrolyte interface and the conductivity of the tissue medium, 2) capacitive modulation of the stimulus waveform, and 3) inhomogeneity and anisotropy of the tissue medium. While the voltage distribution does not directly predict the neural response to DBS, the results of this study do provide foundational building blocks for understanding the electrical parameters of DBS and characterizing its effects on the nervous system.

Depletion of angiotensin-converting enzyme 2 reduces brain serotonin and impairs the running-induced neurogenic response.

PubMed

Klempin, Friederike; Mosienko, Valentina; Matthes, Susann; Villela, Daniel C; Todiras, Mihail; Penninger, Josef M; Bader, Michael; Santos, Robson A S; Alenina, Natalia

2018-04-20

Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1-7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1-7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism.

Innate Immunity and Inflammation Post-Stroke: An α7-Nicotinic Agonist Perspective

PubMed Central

Neumann, Silke; Shields, Nicholas J.; Balle, Thomas; Chebib, Mary; Clarkson, Andrew N.

2015-01-01

Stroke is one of the leading causes of death and long-term disability, with limited treatment options available. Inflammation contributes to damage tissue in the central nervous system across a broad range of neuropathologies, including Alzheimer’s disease, pain, Schizophrenia, and stroke. While the immune system plays an important role in contributing to brain damage produced by ischemia, the damaged brain, in turn, can exert a powerful immune-suppressive effect that promotes infections and threatens the survival of stroke patients. Recently the cholinergic anti-inflammatory pathway, in particular its modulation using α7-nicotinic acetylcholine receptor (α7-nAChR) ligands, has shown potential as a strategy to dampen the inflammatory response and facilitate functional recovery in stroke patients. Here we discuss the current literature on stroke-induced inflammation and the effects of α7-nAChR modulators on innate immune cells. PMID:26690125

Innate Immunity and Inflammation Post-Stroke: An α7-Nicotinic Agonist Perspective.

PubMed

Neumann, Silke; Shields, Nicholas J; Balle, Thomas; Chebib, Mary; Clarkson, Andrew N

2015-12-04

Stroke is one of the leading causes of death and long-term disability, with limited treatment options available. Inflammation contributes to damage tissue in the central nervous system across a broad range of neuropathologies, including Alzheimer's disease, pain, Schizophrenia, and stroke. While the immune system plays an important role in contributing to brain damage produced by ischemia, the damaged brain, in turn, can exert a powerful immune-suppressive effect that promotes infections and threatens the survival of stroke patients. Recently the cholinergic anti-inflammatory pathway, in particular its modulation using α7-nicotinic acetylcholine receptor (α7-nAChR) ligands, has shown potential as a strategy to dampen the inflammatory response and facilitate functional recovery in stroke patients. Here we discuss the current literature on stroke-induced inflammation and the effects of α7-nAChR modulators on innate immune cells.

Preoptic leptin signaling modulates energy balance independent of body temperature regulation.

PubMed

Yu, Sangho; Cheng, Helia; François, Marie; Qualls-Creekmore, Emily; Huesing, Clara; He, Yanlin; Jiang, Yanyan; Gao, Hong; Xu, Yong; Zsombok, Andrea; Derbenev, Andrei V; Nillni, Eduardo A; Burk, David H; Morrison, Christopher D; Berthoud, Hans-Rudolf; Münzberg, Heike

2018-05-15

The adipokine leptin acts on the brain to regulate energy balance but specific functions in many brain areas remain poorly understood. Among these, the preoptic area (POA) is well known to regulate core body temperature by controlling brown fat thermogenesis, and we have previously shown that glutamatergic, long-form leptin receptor (Lepr)-expressing neurons in the POA are stimulated by warm ambient temperature and suppress energy expenditure and food intake. Here we further investigate the role of POA leptin signaling in body weight regulation and its relationship to body temperature regulation in mice. We show that POA Lepr signaling modulates energy expenditure in response to internal energy state, and thus contributes to body weight homeostasis. However, POA leptin signaling is not involved in ambient temperature-dependent metabolic adaptations. Our study reveals a novel cell population through which leptin regulates body weight. © 2018, Yu et al.

Mindfulness meditation-related pain relief: Evidence for unique brain mechanisms in the regulation of pain

PubMed Central

Zeidan, F.; Grant, J.A.; Brown, C.A.; McHaffie, J.G.; Coghill, R.C.

2013-01-01

The cognitive modulation of pain is influenced by a number of factors ranging from attention, beliefs, conditioning, expectations, mood, and the regulation of emotional responses to noxious sensory events. Recently, mindfulness meditation has been found attenuate pain through some of these mechanisms including enhanced cognitive and emotional control, as well as altering the contextual evaluation of sensory events. This review discusses the brain mechanisms involved in mindfulness meditation-related pain relief across different meditative techniques, expertise and training levels, experimental procedures, and neuroimaging methodologies. Converging lines of neuroimaging evidence reveal that mindfulness meditation-related pain relief is associated with unique appraisal cognitive processes depending on expertise level and meditation tradition. Moreover, it is postulated that mindfulness meditation-related pain relief may share a common final pathway with other cognitive techniques in the modulation of pain. PMID:22487846

Consumption of fermented milk product with probiotic modulates brain activity.

PubMed

Tillisch, Kirsten; Labus, Jennifer; Kilpatrick, Lisa; Jiang, Zhiguo; Stains, Jean; Ebrat, Bahar; Guyonnet, Denis; Legrain-Raspaud, Sophie; Trotin, Beatrice; Naliboff, Bruce; Mayer, Emeran A

2013-06-01

Changes in gut microbiota have been reported to alter signaling mechanisms, emotional behavior, and visceral nociceptive reflexes in rodents. However, alteration of the intestinal microbiota with antibiotics or probiotics has not been shown to produce these changes in humans. We investigated whether consumption of a fermented milk product with probiotic (FMPP) for 4 weeks by healthy women altered brain intrinsic connectivity or responses to emotional attention tasks. Healthy women with no gastrointestinal or psychiatric symptoms were randomly assigned to groups given FMPP (n = 12), a nonfermented milk product (n = 11, controls), or no intervention (n = 13) twice daily for 4 weeks. The FMPP contained Bifidobacterium animalis subsp Lactis, Streptococcus thermophiles, Lactobacillus bulgaricus, and Lactococcus lactis subsp Lactis. Participants underwent functional magnetic resonance imaging before and after the intervention to measure brain response to an emotional faces attention task and resting brain activity. Multivariate and region of interest analyses were performed. FMPP intake was associated with reduced task-related response of a distributed functional network (49% cross-block covariance; P = .004) containing affective, viscerosensory, and somatosensory cortices. Alterations in intrinsic activity of resting brain indicated that ingestion of FMPP was associated with changes in midbrain connectivity, which could explain the observed differences in activity during the task. Four-week intake of an FMPP by healthy women affected activity of brain regions that control central processing of emotion and sensation. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

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.

DAT Genotype Modulates Brain and Behavioral Responses Elicited by Cigarette Cues

PubMed Central

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

2011-01-01

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

Pain when love is near

NASA Astrophysics Data System (ADS)

Tamam, S.; Ahmad, A. H.; Aziz, M. E.; Kamil, W. A.

2017-05-01

The aim of the study is to investigate brain responses to acute laser pain when a loved one is nearby. Laser pain stimuli at individual pain threshold were delivered using Th:YAG laser to 17 female participants. The participants were categorised into two groups, Love Hurts or Love Heals, according to their responses to pain stimulation during the presence of their loved ones. fMRI brain activation was obtained using 3 T Philips Achieva MRI scanner utilising blocked design paradigm comprising 15 blocks of stimulation phase and 15 blocks of no stimulation. fMRI images were analysed using statistical parametric mapping (SPM) focusing on random effects (RFX) analysis. We found that both groups activated pain-related areas such as the thalamus, secondary somatosensory cortex, insula and cingulate cortex. However, Love Hurts showed more activity in thalamus, parahippocampal gyrus and hippocampus; while Love Heals showed more activity in the entire part of cingulate cortex during the presence of their loved ones. In conclusion, there may be specific brain regions responsible for modulation of pain due to the presence of a loved one thus manifesting as Love Hurts or Love Heals.

Depression and treatment response: dynamic interplay of signaling pathways and altered neural processes

PubMed Central

Duric, Vanja

2014-01-01

Since the 1960s, when the first tricyclic and monoamine oxidase inhibitor antidepressant drugs were introduced, most of the ensuing agents were designed to target similar brain pathways that elevate serotonin and/or norepinephrine signaling. Fifty years later, the main goal of the current depression research is to develop faster-acting, more effective therapeutic agents with fewer side effects, as currently available antidepressants are plagued by delayed therapeutic onset and low response rates. Clinical and basic science research studies have made significant progress towards deciphering the pathophysiological events within the brain involved in development, maintenance, and treatment of major depressive disorder. Imaging and postmortem brain studies in depressed human subjects, in combination with animal behavioral models of depression, have identified a number of different cellular events, intracellular signaling pathways, proteins, and target genes that are modulated by stress and are potentially vital mediators of antidepressant action. In this review, we focus on several neural mechanisms, primarily within the hippocampus and prefrontal cortex, which have recently been implicated in depression and treatment response. PMID:22585060

Distinct representations of configural and part information across multiple face-selective regions of the human brain

PubMed Central

Golarai, Golijeh; Ghahremani, Dara G.; Eberhardt, Jennifer L.; Gabrieli, John D. E.

2015-01-01

Several regions of the human brain respond more strongly to faces than to other visual stimuli, such as regions in the amygdala (AMG), superior temporal sulcus (STS), and the fusiform face area (FFA). It is unclear if these brain regions are similar in representing the configuration or natural appearance of face parts. We used functional magnetic resonance imaging of healthy adults who viewed natural or schematic faces with internal parts that were either normally configured or randomly rearranged. Response amplitudes were reduced in the AMG and STS when subjects viewed stimuli whose configuration of parts were digitally rearranged, suggesting that these regions represent the 1st order configuration of face parts. In contrast, response amplitudes in the FFA showed little modulation whether face parts were rearranged or if the natural face parts were replaced with lines. Instead, FFA responses were reduced only when both configural and part information were reduced, revealing an interaction between these factors, suggesting distinct representation of 1st order face configuration and parts in the AMG and STS vs. the FFA. PMID:26594191

Activity in the human brain predicting differential heart rate responses to emotional facial expressions.

PubMed

Critchley, Hugo D; Rotshtein, Pia; Nagai, Yoko; O'Doherty, John; Mathias, Christopher J; Dolan, Raymond J

2005-02-01

The James-Lange theory of emotion proposes that automatically generated bodily reactions not only color subjective emotional experience of stimuli, but also necessitate a mechanism by which these bodily reactions are differentially generated to reflect stimulus quality. To examine this putative mechanism, we simultaneously measured brain activity and heart rate to identify regions where neural activity predicted the magnitude of heart rate responses to emotional facial expressions. Using a forewarned reaction time task, we showed that orienting heart rate acceleration to emotional face stimuli was modulated as a function of the emotion depicted. The magnitude of evoked heart rate increase, both across the stimulus set and within each emotion category, was predicted by level of activity within a matrix of interconnected brain regions, including amygdala, insula, anterior cingulate, and brainstem. We suggest that these regions provide a substrate for translating visual perception of emotional facial expression into differential cardiac responses and thereby represent an interface for selective generation of visceral reactions that contribute to the embodied component of emotional reaction.

Amygdala responses to unpleasant pictures are influenced by task demands and positive affect trait

PubMed Central

Sanchez, Tiago A.; Mocaiber, Izabela; Erthal, Fatima S.; Joffily, Mateus; Volchan, Eliane; Pereira, Mirtes G.; de Araujo, Draulio B.; Oliveira, Leticia

2015-01-01

The role of attention in emotional processing is still the subject of debate. Recent studies have found that high positive affect in approach motivation narrows attention. Furthermore, the positive affect trait has been suggested as an important component for determining human variability in threat reactivity. We employed functional magnetic resonance imaging to investigate whether different states of attention control would modulate amygdala responses to highly unpleasant pictures relative to neutral and whether this modulation would be influenced by the positive affect trait. Participants (n = 22, 12 male) were scanned while viewing neutral (people) or unpleasant pictures (mutilated bodies) flanked by two peripheral bars. They were instructed to (a) judge the picture content as unpleasant or neutral or (b) to judge the difference in orientation between the bars in an easy condition (0 or 90∘ orientation difference) or (c) in a hard condition (0 or 6∘ orientation difference). Whole brain analysis revealed a task main effect of brain areas related to the experimental manipulation of attentional control, including the amygdala, dorsolateral prefrontal cortex, and posterior parietal cortex. Region of interest analysis showed an inverse correlation (r = -0.51, p < 0.01) between left amygdala activation and positive affect level when participants viewed unpleasant stimuli and judged bar orientation in the easy condition. This result suggests that subjects with high positive affect exhibit lower amygdala reactivity to distracting unpleasant pictures. In conclusion, the current study suggests that positive affect modulates attention effect on unpleasant pictures, therefore attenuating emotional responses. PMID:25788883

Psychosocial Stress and Brain Function in Adolescent Psychopathology.

PubMed

Quinlan, Erin Burke; Cattrell, Anna; Jia, Tianye; Artiges, Eric; Banaschewski, Tobias; Barker, Gareth; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Brühl, Rüdiger; Conrod, Patricia J; Desrivieres, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Martinot, Jean-Luc; Paillère Martinot, Marie-Laure; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Paus, Tomáš; Poustka, Luise; Smolka, Michael N; Vetter, Nora C; Walter, Henrik; Whelan, Robert; Glennon, Jeffrey C; Buitelaar, Jan K; Happé, Francesca; Loth, Eva; Barker, Edward D; Schumann, Gunter

2017-08-01

The authors sought to explore how conduct, hyperactivity/inattention, and emotional symptoms are associated with neural reactivity to social-emotional stimuli, and the extent to which psychosocial stress modulates these relationships. Participants were community adolescents recruited as part of the European IMAGEN study. Bilateral amygdala regions of interest were used to assess the relationship between the three symptom domains and functional MRI neural reactivity during passive viewing of dynamic angry and neutral facial expressions. Exploratory functional connectivity and whole brain multiple regression approaches were used to analyze how the symptoms and psychosocial stress relate to other brain regions. In response to the social-emotional stimuli, adolescents with high levels of conduct or hyperactivity/inattention symptoms who had also experienced a greater number of stressful life events showed hyperactivity of the amygdala and several regions across the brain. This effect was not observed with emotional symptoms. A cluster in the midcingulate was found to be common to both conduct problems and hyperactivity symptoms. Exploratory functional connectivity analyses suggested that amygdala-precuneus connectivity is associated with hyperactivity/inattention symptoms. The results link hyperactive amygdala responses and regions critical for top-down emotional processing with high levels of psychosocial stress in individuals with greater conduct and hyperactivity/inattention symptoms. This work highlights the importance of studying how psychosocial stress affects functional brain responses to social-emotional stimuli, particularly in adolescents with externalizing symptoms.

Network-dependent modulation of brain activity during sleep.

PubMed

Watanabe, Takamitsu; Kan, Shigeyuki; Koike, Takahiko; Misaki, Masaya; Konishi, Seiki; Miyauchi, Satoru; Miyahsita, Yasushi; Masuda, Naoki

2014-09-01

Brain activity dynamically changes even during sleep. A line of neuroimaging studies has reported changes in functional connectivity and regional activity across different sleep stages such as slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. However, it remains unclear whether and how the large-scale network activity of human brains changes within a given sleep stage. Here, we investigated modulation of network activity within sleep stages by applying the pairwise maximum entropy model to brain activity obtained by functional magnetic resonance imaging from sleeping healthy subjects. We found that the brain activity of individual brain regions and functional interactions between pairs of regions significantly increased in the default-mode network during SWS and decreased during REM sleep. In contrast, the network activity of the fronto-parietal and sensory-motor networks showed the opposite pattern. Furthermore, in the three networks, the amount of the activity changes throughout REM sleep was negatively correlated with that throughout SWS. The present findings suggest that the brain activity is dynamically modulated even in a sleep stage and that the pattern of modulation depends on the type of the large-scale brain networks. Copyright © 2014 Elsevier Inc. All rights reserved.

On the dependence of response inhibition processes on sensory modality.

PubMed

Bodmer, Benjamin; Beste, Christian

2017-04-01

The ability to inhibit responses is a central sensorimotor function but only recently the importance of sensory processes for motor inhibition mechanisms went more into the research focus. In this regard it is elusive, whether there are differences between sensory modalities to trigger response inhibition processes. Due to functional neuroanatomical considerations strong differences may exist, for example, between the visual and the tactile modality. In the current study we examine what neurophysiological mechanisms as well as functional neuroanatomical networks are modulated during response inhibition. Therefore, a Go/NoGo-paradigm employing a novel combination of visual, tactile, and visuotactile stimuli was used. The data show that the tactile modality is more powerful than the visual modality to trigger response inhibition processes. However, the tactile modality loses its efficacy to trigger response inhibition processes when being combined with the visual modality. This may be due to competitive mechanisms leading to a suppression of certain sensory stimuli and the response selection level. Variations in sensory modalities specifically affected conflict monitoring processes during response inhibition by modulating activity in a frontal parietal network including the right inferior frontal gyrus, anterior cingulate cortex and the temporoparietal junction. Attentional selection processes are not modulated. The results suggest that the functional neuroanatomical networks involved in response inhibition critically depends on the nature of the sensory input. Hum Brain Mapp 38:1941-1951, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Gut Microbes and the Brain: Paradigm Shift in Neuroscience

PubMed Central

Knight, Rob; Mazmanian, Sarkis K.; Cryan, John F.; Tillisch, Kirsten

2014-01-01

The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject. PMID:25392516

Hybrid Neuroprosthesis for the Upper Limb: Combining Brain-Controlled Neuromuscular Stimulation with a Multi-Joint Arm Exoskeleton

PubMed Central

Grimm, Florian; Walter, Armin; Spüler, Martin; Naros, Georgios; Rosenstiel, Wolfgang; Gharabaghi, Alireza

2016-01-01

Brain-machine interface-controlled (BMI) neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion (ROM) and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES) is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task-related ROM and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton) in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity-compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. NMES was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD) and electromyography (EMG) activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e., induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p = 0.028) or EMG (p = 0.021) modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related ROM (p = 0.009) and the movement-related brain modulation (p = 0.019). Combining a hybrid BMI with neuromuscular stimulation and antigravity assistance augments upper limb function and brain activity during rehabilitation exercises and may thus provide a novel restorative framework for severely affected stroke patients. PMID:27555805

Hybrid Neuroprosthesis for the Upper Limb: Combining Brain-Controlled Neuromuscular Stimulation with a Multi-Joint Arm Exoskeleton.

PubMed

Grimm, Florian; Walter, Armin; Spüler, Martin; Naros, Georgios; Rosenstiel, Wolfgang; Gharabaghi, Alireza

2016-01-01

Brain-machine interface-controlled (BMI) neurofeedback training aims to modulate cortical physiology and is applied during neurorehabilitation to increase the responsiveness of the brain to subsequent physiotherapy. In a parallel line of research, robotic exoskeletons are used in goal-oriented rehabilitation exercises for patients with severe motor impairment to extend their range of motion (ROM) and the intensity of training. Furthermore, neuromuscular electrical stimulation (NMES) is applied in neurologically impaired patients to restore muscle strength by closing the sensorimotor loop. In this proof-of-principle study, we explored an integrated approach for providing assistance as needed to amplify the task-related ROM and the movement-related brain modulation during rehabilitation exercises of severely impaired patients. For this purpose, we combined these three approaches (BMI, NMES, and exoskeleton) in an integrated neuroprosthesis and studied the feasibility of this device in seven severely affected chronic stroke patients who performed wrist flexion and extension exercises while receiving feedback via a virtual environment. They were assisted by a gravity-compensating, seven degree-of-freedom exoskeleton which was attached to the paretic arm. NMES was applied to the wrist extensor and flexor muscles during the exercises and was controlled by a hybrid BMI based on both sensorimotor cortical desynchronization (ERD) and electromyography (EMG) activity. The stimulation intensity was individualized for each targeted muscle and remained subthreshold, i.e., induced no overt support. The hybrid BMI controlled the stimulation significantly better than the offline analyzed ERD (p = 0.028) or EMG (p = 0.021) modality alone. Neuromuscular stimulation could be well integrated into the exoskeleton-based training and amplified both the task-related ROM (p = 0.009) and the movement-related brain modulation (p = 0.019). Combining a hybrid BMI with neuromuscular stimulation and antigravity assistance augments upper limb function and brain activity during rehabilitation exercises and may thus provide a novel restorative framework for severely affected stroke patients.

Noninvasive transcranial focused ultrasonic-magnetic stimulation for modulating brain oscillatory activity

NASA Astrophysics Data System (ADS)

Yuan, Yi; Chen, Yudong; Li, Xiaoli

2016-02-01

A novel technique, transcranial focused ultrasonic-magnetic stimulation (tFUMS), has been developed for noninvasive brain modulation in vivo. tFUMS has a higher spatial resolution (<2 mm) and a higher penetration depth than other noninvasive neuromodulation methods. The in vivo animal experimental results show that tFUMS can not only increase the power of local field potentials and the firing rate of the neurons, but also enhance the effect of transcranial focused ultrasound stimulation on the neuromodulation. The results demonstrate that tFUMS can modulate brain oscillatory activities by stimulating brain tissues.

A Unique Four-Hub Protein Cluster Associates to Glioblastoma Progression

PubMed Central

Simeone, Pasquale; Trerotola, Marco; Urbanella, Andrea; Lattanzio, Rossano; Ciavardelli, Domenico; Di Giuseppe, Fabrizio; Eleuterio, Enrica; Sulpizio, Marilisa; Eusebi, Vincenzo; Pession, Annalisa; Piantelli, Mauro; Alberti, Saverio

2014-01-01

Gliomas are the most frequent brain tumors. Among them, glioblastomas are malignant and largely resistant to available treatments. Histopathology is the gold standard for classification and grading of brain tumors. However, brain tumor heterogeneity is remarkable and histopathology procedures for glioma classification remain unsatisfactory for predicting disease course as well as response to treatment. Proteins that tightly associate with cancer differentiation and progression, can bear important prognostic information. Here, we describe the identification of protein clusters differentially expressed in high-grade versus low-grade gliomas. Tissue samples from 25 high-grade tumors, 10 low-grade tumors and 5 normal brain cortices were analyzed by 2D-PAGE and proteomic profiling by mass spectrometry. This led to identify 48 differentially expressed protein markers between tumors and normal samples. Protein clustering by multivariate analyses (PCA and PLS-DA) provided discrimination between pathological samples to an unprecedented extent, and revealed a unique network of deranged proteins. We discovered a novel glioblastoma control module centered on four major network hubs: Huntingtin, HNF4α, c-Myc and 14-3-3ζ. Immunohistochemistry, western blotting and unbiased proteome-wide meta-analysis revealed altered expression of this glioblastoma control module in human glioma samples as compared with normal controls. Moreover, the four-hub network was found to cross-talk with both p53 and EGFR pathways. In summary, the findings of this study indicate the existence of a unifying signaling module controlling glioblastoma pathogenesis and malignant progression, and suggest novel targets for development of diagnostic and therapeutic procedures. PMID:25050814

PCB disruption of the hypothalamus-pituitary-interrenal axis involves brain glucocorticoid receptor downregulation in anadromous Arctic charr

USGS Publications Warehouse

Aluru, N.; Jorgensen, E.H.; Maule, A.G.; Vijayan, M.M.

2004-01-01

We examined whether brain glucocorticoid receptor (GR) modulation by polychlorinated biphenyls (PCBs) was involved in the abnormal cortisol response to stress seen in anadromous Arctic charr (Salvelinus alpinus). Fish treated with Aroclor 1254 (0, 1, 10, and 100 mg/kg body mass) were maintained for 5 mo without feeding in the winter to mimic their seasonal fasting cycle, whereas a fed group with 0 and 100 mg/kg Aroclor was maintained for comparison. Fasting elevated plasma cortisol levels and brain GR content but depressed heat shock protein 90 (hsp90) and interrenal cortisol production capacity. Exposure of fasted fish to Aroclor 1254 resulted in a dose-dependent increase in brain total PCB content. This accumulation in fish with high PCB dose was threefold higher in fasted fish compared with fed fish. PCBs depressed plasma cortisol levels but did not affect in vitro interrenal cortisol production capacity in fasted charr. At high PCB dose, the brain GR content was significantly lower in the fasted fish and this corresponded with a lower brain hsp70 and hsp90 content. The elevation of plasma cortisol levels and upregulation of brain GR content may be an important adaptation to extended fasting in anadromous Arctic charr, and this response was disrupted by PCBs. Taken together, the hypothalamus-pituitary- interrenal axis is a target for PCB impact during winter emaciation in anadromous Arctic charr.

Frequency analysis of the visual steady-state response measured with the fast optical signal in younger and older adults.

PubMed

Tse, Chun-Yu; Gordon, Brian A; Fabiani, Monica; Gratton, Gabriele

2010-09-01

Relatively high frequency activity (>4Hz) carries important information about the state of the brain or its response to high frequency events. The electroencephalogram (EEG) is commonly used to study these changes because it possesses high temporal resolution and a good signal-to-noise ratio. However, it provides limited spatial information. Non-invasive fast optical signals (FOS) have been proposed as a neuroimaging tool combining spatial and temporal resolution. Yet, this technique has not been applied to study high frequency brain oscillations because of its relatively low signal-to-noise ratio. Here we investigate the sensitivity of FOS to relatively high-frequency brain oscillations. We measured the steady-state optical response elicited in medial and lateral occipital cortex by checkerboard reversals occurring at 4, 6, and 8Hz in younger and older adults. Stimulus-dependent oscillations were observed at the predicted stimulation frequency. In addition, in the younger adults the FOS steady-state response was smaller in lateral than medial areas, whereas in the older adults it was reversed in these two cortical regions. This may reflect diminished top-down inhibitory control in the older adults. The results indicate that FOS can be used to study the modulation of relatively high-frequency brain oscillations in adjacent cortical regions. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Designing modulators of 5-hydroxytryptamine signaling to treat abuse disorders.

PubMed

van de Wiel, Sandra M W; Verheij, Michel M; Homberg, Judith R

2014-11-01

There are currently no treatments approved by the FDA to effectively treat cocaine dependence. Research of recent years has gradually revealed the importance of 5-hydroxytryptamine (5-HT) in the reinforcing and rewarding effects of cocaine and the potential for relapse. Brain-derived neurotropic factor (BDNF) is an important modulator of the serotonergic system and 5-HT modulates BDNF expression. Their reciprocal interaction is of crucial importance for synaptic plasticity during long-term cocaine intake. Thus, agents modifying BDNF-5-HT interactions might have therapeutic potential for cocaine dependence by reversing the altered brain structure that underlies relapse after cocaine withdrawal. On the basis of the available literature, the authors propose an interaction between BDNF and the serotonergic system in the response to cocaine and during cocaine intake. Furthermore, they discuss putative therapies that are based on 5-HT and BDNF. Recent studies are beginning to elucidate the role of 5-HT and BDNF in cocaine addiction. Additionally, animal studies modeling addiction-like drug intake will only further help to gain a better understanding of how to treat cocaine addiction. Based on the current evidence, the authors believe that BDNF, as a modulator of the serotonergic pathway, or 5-HT, as a modulator of the BDNF system, represent a valuable target to treat drug addiction, which may yield novel therapeutics in the future.

GAP-43 is essential for the neurotrophic effects of BDNF and positive AMPA receptor modulator S18986.

PubMed

Gupta, S K; Mishra, R; Kusum, S; Spedding, M; Meiri, K F; Gressens, P; Mani, S

2009-04-01

Positive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor modulators include benzamide compounds that allosterically modulate AMPA glutamate receptors. These small molecules that cross the blood-brain barrier have been shown to act as a neuroprotectant by increasing the levels of endogenous brain-derived neurotrophic factor (BDNF). Positive AMPA receptor modulators have also been shown to increase the levels of growth-associated protein-43 (GAP-43). GAP-43 plays a major role in many aspects of neuronal function in vertebrates. The goal of this study was to determine whether GAP-43 was important in mediating the actions of positive AMPA receptor modulator (S18986) and BDNF. Using cortical cultures from GAP-43 knockout and control mice, we show that (1) GAP-43 is upregulated in response to S18986 and BDNF in control cultures; (2) this upregulation of GAP-43 is essential for mediating the neuroprotective effects of S18986 and BDNF; (3) administration of S18986 and BDNF leads to an increase in the expression of the glutamate transporters GLT-1 and GLAST that are key to limiting excitotoxic cell death and this increase in GLT-1 and GLAST expression is completely blocked in the absence of GAP-43. Taken together this study concludes that GAP-43 is an important mediator of the neurotrophic effects of S18986 and BDNF on neuronal survival and plasticity, and is essential for the success of positive AMPA receptor modulator-BDNF-based neurotrophin therapy.

The Use of Functional MRI to Study Appetite Control in the CNS

PubMed Central

De Silva, Akila; Salem, Victoria; Matthews, Paul M.; Dhillo, Waljit S.

2012-01-01

Functional magnetic resonance imaging (fMRI) has provided the opportunity to safely investigate the workings of the human brain. This paper focuses on its use in the field of human appetitive behaviour and its impact in obesity research. In the present absence of any safe or effective centrally acting appetite suppressants, a better understanding of how appetite is controlled is vital for the development of new antiobesity pharmacotherapies. Early functional imaging techniques revealed an attenuation of brain reward area activity in response to visual food stimuli when humans are fed—in other words, the physiological state of hunger somehow increases the appeal value of food. Later studies have investigated the action of appetite modulating hormones on the fMRI signal, showing how the attenuation of brain reward region activity that follows feeding can be recreated in the fasted state by the administration of anorectic gut hormones. Furthermore, differences in brain activity between obese and lean individuals have provided clues about the possible aetiology of overeating. The hypothalamus acts as a central gateway modulating homeostatic and nonhomeostatic drives to eat. As fMRI techniques constantly improve, functional data regarding the role of this small but hugely important structure in appetite control is emerging. PMID:22719753

Decision-making in the adolescent brain.

PubMed

Blakemore, Sarah-Jayne; Robbins, Trevor W

2012-09-01

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

Nutritional Immunity Triggers the Modulation of Iron Metabolism Genes in the Sub-Antarctic Notothenioid Eleginops maclovinus in Response to Piscirickettsia salmonis

PubMed Central

Martínez, Danixa; Oyarzún, Ricardo; Pontigo, Juan Pablo; Romero, Alex; Yáñez, Alejandro J.; Vargas-Chacoff, Luis

2017-01-01

Iron deprivation is a nutritional immunity mechanism through which fish can limit the amount of iron available to invading bacteria. The aim of this study was to evaluate the modulation of iron metabolism genes in the liver and brain of sub-Antarctic notothenioid Eleginops maclovinus challenged with Piscirickettsia salmonis. The specimens were inoculated with two P. salmonis strains: LF-89 (ATCC® VR-1361™) and Austral-005 (antibiotic resistant). Hepatic and brain samples were collected at intervals over a period of 35 days. Gene expression (by RT-qPCR) of proteins involved in iron storage, transport, and binding were statistically modulated in infected fish when compared with control counterparts. Specifically, the expression profiles of the transferrin and hemopexin genes in the liver, as well as the expression profiles of ferritin-M, ferritin-L, and transferrin in the brain, were similar for both experimental groups. Nevertheless, the remaining genes such as ferritin-H, ceruloplasmin, hepcidin, and haptoglobin presented tissue-specific expression profiles that varied in relation to the injected bacterial strain and sampling time-point. These results suggest that nutritional immunity could be an important immune defense mechanism for E. maclovinus against P. salmonis injection. This study provides relevant information for understanding iron metabolism of a sub-Antarctic notothenioid fish. PMID:28974951

Processing of emotional stimuli is reflected by modulations of beta band activity in the subgenual anterior cingulate cortex in patients with treatment resistant depression

PubMed Central

Huebl, Julius; Brücke, Christof; Merkl, Angela; Bajbouj, Malek; Schneider, Gerd-Helge

2016-01-01

Deep brain stimulation (DBS) of the subgenual anterior cingulate cortex (sgACC) has emerged as a new therapeutic option in patients with treatment resistant depression (TRD). At the same time, DBS offers a unique opportunity as an innovative research tool to study brain function in vivo. Indirect measures of brain function such as positron-emission-tomography imaging findings have revealed a hypermetabolism in the sgACC area in patients with TRD that normalizes in parallel with treatment response to DBS. We used direct intracranial recordings via implanted DBS electrodes to study the neuronal oscillatory activity in the sgACC area during a picture viewing task including emotional and neutral stimuli in eight patients with TRD who underwent DBS. We found a stimulus-induced decrease in beta-band and increase in gamma-band activity, with a main effect of valence for event-related desynchronisation in the beta-frequency range (14–30 Hz). Unpleasant stimuli induced the strongest and most sustained beta-power decrease. The degree of beta-band modulation upon emotional stimuli correlated with the patients’ rating of stimulus valence. Our findings confirm the involvement of the sgACC area in emotional processing that was more enhanced for unpleasant stimuli. Moreover, stimulus evaluation may be encoded by modulations of beta-band activity. PMID:27013105

Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus

PubMed Central

Zhang, Jiyong; Sadowska, Grazyna B.; Chen, Xiaodi; Park, Seon Yeong; Kim, Jeong-Eun; Bodge, Courtney A.; Cummings, Erin; Lim, Yow-Pin; Makeyev, Oleksandr; Besio, Walter G.; Gaitanis, John; Banks, William A.; Stonestreet, Barbara S.

2015-01-01

Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti–IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti–IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti–IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia.—Zhang, J., Sadowska, G. B., Chen, X., Park, S. Y., Kim, J.-E., Bodge, C. A., Cummings, E., Lim, Y.-P., Makeyev, O., Besio, W. G., Gaitanis, J., Banks, W. A., Stonestreet, B. S. Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus. PMID:25609424

Previous physical exercise alters the hepatic profile of oxidative-inflammatory status and limits the secondary brain damage induced by severe traumatic brain injury in rats.

PubMed

de Castro, Mauro Robson Torres; Ferreira, Ana Paula de Oliveira; Busanello, Guilherme Lago; da Silva, Luís Roberto Hart; da Silveira Junior, Mauro Eduardo Porto; Fiorin, Fernando da Silva; Arrifano, Gabriela; Crespo-López, Maria Elena; Barcelos, Rômulo Pillon; Cuevas, María J; Bresciani, Guilherme; González-Gallego, Javier; Fighera, Michele Rechia; Royes, Luiz Fernando Freire

2017-09-01

An early inflammatory response and oxidative stress are implicated in the signal transduction that alters both hepatic redox status and mitochondrial function after traumatic brain injury (TBI). Peripheral oxidative/inflammatory responses contribute to neuronal dysfunction after TBI Exercise training alters the profile of oxidative-inflammatory status in liver and protects against acute hyperglycaemia and a cerebral inflammatory response after TBI. Approaches such as exercise training, which attenuates neuronal damage after TBI, may have therapeutic potential through modulation of responses by metabolic organs. The vulnerability of the body to oxidative/inflammatory in TBI is significantly enhanced in sedentary compared to physically active counterparts. Although systemic responses have been described after traumatic brain injury (TBI), little is known regarding potential interactions between brain and peripheral organs after neuronal injury. Accordingly, we aimed to investigate whether a peripheral oxidative/inflammatory response contributes to neuronal dysfunction after TBI, as well as the prophylactic role of exercise training. Animals were submitted to fluid percussion injury after 6 weeks of swimming training. Previous exercise training increased mRNA expression of X receptor alpha and ATP-binding cassette transporter, and decreased inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α and interleukin (IL)-6 expression per se in liver. Interestingly, exercise training protected against hepatic inflammation (COX-2, iNOS, TNF-α and IL-6), oxidative stress (decreases in non-protein sulfhydryl and glutathione, as well as increases in 2',7'-dichlorofluorescein diacetate oxidation and protein carbonyl), which altered hepatic redox status (increases in myeloperoxidase and superoxide dismutase activity, as well as inhibition of catalase activity) mitochondrial function (decreases in methyl-tetrazolium and Δψ, as well as inhibition of citrate synthase activity) and ion gradient homeostasis (inhibition of Na + ,K + -ATPase activity inhibition) when analysed 24 h after TBI. Previous exercise training also protected against dysglycaemia, impaired hepatic signalling (increase in phosphorylated c-Jun NH2-terminal kinase, phosphorylated decreases in insulin receptor substrate and phosphorylated AKT expression), high levels of circulating and neuronal cytokines, the opening of the blood-brain barrier, neutrophil infiltration and Na + ,K + -ATPase activity inhibition in the ipsilateral cortex after TBI. Moreover, the impairment of protein function, neurobehavioural (neuromotor dysfunction and spatial learning) disability and hippocampal cell damage in sedentary rats suggests that exercise training also modulates peripheral oxidative/inflammatory pathways in TBI, which corroborates the ever increasing evidence regarding health-related outcomes with respect to a physically active lifestyle. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

An examination of changes in maternal neuroimmune function during pregnancy and the postpartum period.

PubMed

Sherer, Morgan L; Posillico, Caitlin K; Schwarz, Jaclyn M

2017-11-01

There is strong evidence that the immune system changes dramatically during pregnancy in order to prevent the developing fetus from being "attacked" by the maternal immune system. Due to these alterations in peripheral immune function, many women that suffer from autoimmune disorders actually find significant relief from their symptoms throughout pregnancy; however, these changes can also leave the mother more susceptible to infections that would otherwise be mitigated by the inflammatory response (Robinson and Klein, 2012). Only one other study has looked at changes in microglial number and morphology during pregnancy and the postpartum period (Haim et al., 2016), but no one has yet examined the neuroimmune response following an immune challenge during this time. Therefore, in this study, we investigated the impact of an immune challenge during various time-points throughout pregnancy and the postpartum period on the expression of immune molecules in the brain of the mother and fetus. Our results indicate that similar to the peripheral immune suppression measured during pregnancy, we also see significant suppression of the immune response in the maternal brain, particularly during late gestation. In contrast to the peripheral immune system, immune modulation in the maternal brain extends moderately into the postpartum period. Additionally, we found that the fetal immune response in the brain and placenta is also suppressed just before parturition, suggesting that cytokine production in the fetus and placenta are mirroring the peripheral cytokine response of the mother. Copyright © 2017 Elsevier Inc. All rights reserved.

Cytokines and cytokine networks target neurons to modulate long-term potentiation.

PubMed

Prieto, G Aleph; Cotman, Carl W

2017-04-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytokines and cytokine networks target neurons to modulate long-term potentiation

PubMed Central

Prieto, G. Aleph; Cotman, Carl W.

2017-01-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. PMID:28377062

Input-Specific Gain Modulation by Local Sensory Context Shapes Cortical and Thalamic Responses to Complex Sounds.

PubMed

Williamson, Ross S; Ahrens, Misha B; Linden, Jennifer F; Sahani, Maneesh

2016-07-20

Sensory neurons are customarily characterized by one or more linearly weighted receptive fields describing sensitivity in sensory space and time. We show that in auditory cortical and thalamic neurons, the weight of each receptive field element depends on the pattern of sound falling within a local neighborhood surrounding it in time and frequency. Accounting for this change in effective receptive field with spectrotemporal context improves predictions of both cortical and thalamic responses to stationary complex sounds. Although context dependence varies among neurons and across brain areas, there are strong shared qualitative characteristics. In a spectrotemporally rich soundscape, sound elements modulate neuronal responsiveness more effectively when they coincide with sounds at other frequencies, and less effectively when they are preceded by sounds at similar frequencies. This local-context-driven lability in the representation of complex sounds-a modulation of "input-specific gain" rather than "output gain"-may be a widespread motif in sensory processing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Culture modulates the brain response to human expressions of emotion: electrophysiological evidence.

PubMed

Liu, Pan; Rigoulot, Simon; Pell, Marc D

2015-01-01

To understand how culture modulates on-line neural responses to social information, this study compared how individuals from two distinct cultural groups, English-speaking North Americans and Chinese, process emotional meanings of multi-sensory stimuli as indexed by both behaviour (accuracy) and event-related potential (N400) measures. In an emotional Stroop-like task, participants were presented face-voice pairs expressing congruent or incongruent emotions in conditions where they judged the emotion of one modality while ignoring the other (face or voice focus task). Results indicated that while both groups were sensitive to emotional differences between channels (with lower accuracy and higher N400 amplitudes for incongruent face-voice pairs), there were marked group differences in how intruding facial or vocal cues affected accuracy and N400 amplitudes, with English participants showing greater interference from irrelevant faces than Chinese. Our data illuminate distinct biases in how adults from East Asian versus Western cultures process socio-emotional cues, supplying new evidence that cultural learning modulates not only behaviour, but the neurocognitive response to different features of multi-channel emotion expressions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Low-frequency brain stimulation to the left dorsolateral prefrontal cortex increases the negative impact of social exclusion among those high in personal distress.

PubMed

Fitzgibbon, Bernadette Mary; Kirkovski, Melissa; Bailey, Neil Wayne; Thomson, Richard Hilton; Eisenberger, Naomi; Enticott, Peter Gregory; Fitzgerald, Paul Bernard

2017-06-01

The dorsolateral prefrontal cortex (DLPFC) is thought to play a key role in the cognitive control of emotion and has therefore, unsurprisingly, been implicated in the regulation of physical pain perception. This brain region may also influence the experience of social pain, which has been shown to activate similar neural networks as seen in response to physical pain. Here, we applied sham or active low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC, previously shown to exert bilateral effects in pain perception, in healthy participants. Following stimulation, participants played the "Cyberball Task"; an online ball-tossing game in which the subject participant is included or excluded. Compared to sham, rTMS did not modulate behavioural response to social exclusion. However, within the active rTMS group only, greater trait personal distress was related to enhanced negative outcomes to social exclusion. These results add further support to the notion that the effect of brain stimulation is not homogenous across individuals, and indicates the need to consider baseline individual differences when assessing response to brain stimulation. This seems particularly relevant in social neuroscience investigations, where trait factors may have a meaningful effect.

Nonlinear response of the anterior cingulate and prefrontal cortex in schizophrenia as a function of variable attentional control.

PubMed

Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Caforio, Grazia; Romano, Raffaella; Lobianco, Luciana; Fazio, Leonardo; Di Giorgio, Annabella; Latorre, Valeria; Sambataro, Fabio; Popolizio, Teresa; Nardini, Marcello; Mattay, Venkata S; Weinberger, Daniel R; Bertolino, Alessandro

2010-04-01

Previous studies have reported abnormal prefrontal and cingulate activity during attentional control processing in schizophrenia. However, it is not clear how variation in attentional control load modulates activity within these brain regions in this brain disorder. The aim of this study in schizophrenia is to investigate the impact of increasing levels of attentional control processing on prefrontal and cingulate activity. Blood oxygen level-dependent (BOLD) responses of 16 outpatients with schizophrenia were compared with those of 21 healthy subjects while performing a task eliciting increasing levels of attentional control during event-related functional magnetic resonance imaging at 3 T. Results showed reduced behavioral performance in patients at greater attentional control levels. Imaging data indicated greater prefrontal activity at intermediate attentional control levels in patients but greater prefrontal and cingulate responses at high attentional control demands in controls. The BOLD activity profile of these regions in controls increased linearly with increasing cognitive loads, whereas in patients, it was nonlinear. Correlation analysis consistently showed differential region and load-specific relationships between brain activity and behavior in the 2 groups. These results indicate that varying attentional control load is associated in schizophrenia with load- and region-specific modification of the relationship between behavior and brain activity, possibly suggesting earlier saturation of cognitive capacity.

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.

Resting state functional MRI in Parkinson’s disease: the impact of deep brain stimulation on ‘effective’ connectivity

PubMed Central

Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl

2014-01-01

Depleted of dopamine, the dynamics of the parkinsonian brain impact on both ‘action’ and ‘resting’ motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the ‘effective’ connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network—disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses. PMID:24566670

Inhibition of angiogenesis and tumor growth in the brain. Suppression of endothelial cell turnover by penicillamine and the depletion of copper, an angiogenic cofactor.

PubMed Central

Brem, S. S.; Zagzag, D.; Tsanaclis, A. M.; Gately, S.; Elkouby, M. P.; Brien, S. E.

1990-01-01

Microvascular proliferation, a hallmark of malignant brain tumors, represents an attractive target of anticancer research, especially because of the quiescent nonproliferative endothelium of the normal brain. Cerebral neoplasms sequester copper, a trace metal that modulates angiogenesis. Using a rabbit brain tumor model, normocupremic animals developed large vascularized VX2 carcinomas. By contrast, small, circumscribed, relatively avascular tumors were found in the brains of rabbits copper-depleted by diet and penicillamine treatment (CDPT). The CDPT rabbits showed a significant decrease in serum copper, copper staining of tumor cell nuclei, microvascular density, the tumor volume, endothelial cell turnover, and an increase in the vascular permeability (breakdown of the blood-brain barrier), as well as peritumoral brain edema. In non-tumor-bearing animals, CDPT did not alter the vascular permeability or the brain water content. CDPT also inhibited the intracerebral growth of the 9L gliosarcoma in F-344 rats, with a similar increase of the peritumoral vascular permeability and the brain water content. CDPT failed to inhibit tumor growth and the vascularization of the VX2 carcinoma in the thigh muscle or the metastases to the lung, findings that may reflect regional differences in the responsiveness of the endothelium, the distribution of copper, or the activity of cuproenzymes. Metabolic and pharmacologic withdrawal of copper suppresses intracerebral tumor angiogenesis; angiosuppression is a novel biologic response modifier for the in situ control of tumor growth in the brain. Images Figure 2 Figure 4 Figure 5 Figure 6 Figure 8 Figure 10 Figure 12 Figure 15 Figure 16 PMID:1700617

Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

PubMed

Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom

2014-04-01

Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

Odor Valence Linearly Modulates Attractiveness, but Not Age Assessment, of Invariant Facial Features in a Memory-Based Rating Task

PubMed Central

Seubert, Janina; Gregory, Kristen M.; Chamberland, Jessica; Dessirier, Jean-Marc; Lundström, Johan N.

2014-01-01

Scented cosmetic products are used across cultures as a way to favorably influence one's appearance. While crossmodal effects of odor valence on perceived attractiveness of facial features have been demonstrated experimentally, it is unknown whether they represent a phenomenon specific to affective processing. In this experiment, we presented odors in the context of a face battery with systematic feature manipulations during a speeded response task. Modulatory effects of linear increases of odor valence were investigated by juxtaposing subsequent memory-based ratings tasks – one predominantly affective (attractiveness) and a second, cognitive (age). The linear modulation pattern observed for attractiveness was consistent with additive effects of face and odor appraisal. Effects of odor valence on age perception were not linearly modulated and may be the result of cognitive interference. Affective and cognitive processing of faces thus appear to differ in their susceptibility to modulation by odors, likely as a result of privileged access of olfactory stimuli to affective brain networks. These results are critically discussed with respect to potential biases introduced by the preceding speeded response task. PMID:24874703

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

PubMed

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

2017-01-15

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

Linear transformation of the encoding mechanism for light intensity underlies the paradoxical enhancement of cortical visual responses by sevoflurane.

PubMed

Arena, Alessandro; Lamanna, Jacopo; Gemma, Marco; Ripamonti, Maddalena; Ravasio, Giuliano; Zimarino, Vincenzo; De Vitis, Assunta; Beretta, Luigi; Malgaroli, Antonio

2017-01-01

The mechanisms of action of anaesthetics on the living brain are still poorly understood. In this respect, the analysis of the differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity might provide important and novel cues. Here we show that the anaesthetic sevoflurane strongly silences the brain but potentiates in a dose- and frequency-dependent manner the cortical visual response. Such enhancement arises from a linear scaling by sevoflurane of the power-law relation between light intensity and the cortical response. The fingerprint of sevoflurane action suggests that circuit silencing can boost linearly synaptic responsiveness presumably by scaling the number of responding units and/or their correlation following a sensory stimulation. General anaesthetics, which are expected to silence brain activity, often spare sensory responses. To evaluate differential effects of anaesthetics on spontaneous and sensory-evoked cortical activity, we characterized their modulation by sevoflurane and propofol. Power spectra and the bust-suppression ratio from EEG data were used to evaluate anaesthesia depth. ON and OFF cortical responses were elicited by light pulses of variable intensity, duration and frequency, during light and deep states of anaesthesia. Both anaesthetics reduced spontaneous cortical activity but sevoflurane greatly enhanced while propofol diminished the ON visual response. Interestingly, the large potentiation of the ON visual response by sevoflurane was found to represent a linear scaling of the encoding mechanism for light intensity. To the contrary, the OFF cortical visual response was depressed by both anaesthetics. The selective depression of the OFF component by sevoflurane could be converted into a robust potentiation by the pharmacological blockade of the ON pathway, suggesting that the temporal order of ON and OFF responses leads to a depression of the latter. This hypothesis agrees with the finding that the enhancement of the ON response was converted into a depression by increasing the frequency of light-pulse stimulation from 0.1 to 1 Hz. Overall, our results support the view that inactivity-dependent modulation of cortical circuits produces an increase in their responsiveness. Among the implications of our findings, the silencing of cortical circuits can boost linearly the cortical responsiveness but with negative impact on their frequency transfer and with a loss of the information content of the sensory signal. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.

PubMed

Perez-Rodriguez, M Mercedes; New, Antonia S; Goldstein, Kim E; Rosell, Daniel; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David; Siever, Larry J; Hazlett, Erin A

2017-05-30

A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype. Copyright © 2017. Published by Elsevier B.V.

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.

Visual attention modulates brain activation to angry voices.

PubMed

Mothes-Lasch, Martin; Mentzel, Hans-Joachim; Miltner, Wolfgang H R; Straube, Thomas

2011-06-29

In accordance with influential models proposing prioritized processing of threat, previous studies have shown automatic brain responses to angry prosody in the amygdala and the auditory cortex under auditory distraction conditions. However, it is unknown whether the automatic processing of angry prosody is also observed during cross-modal distraction. The current fMRI study investigated brain responses to angry versus neutral prosodic stimuli during visual distraction. During scanning, participants were exposed to angry or neutral prosodic stimuli while visual symbols were displayed simultaneously. By means of task requirements, participants either attended to the voices or to the visual stimuli. While the auditory task revealed pronounced activation in the auditory cortex and amygdala to angry versus neutral prosody, this effect was absent during the visual task. Thus, our results show a limitation of the automaticity of the activation of the amygdala and auditory cortex to angry prosody. The activation of these areas to threat-related voices depends on modality-specific attention.

Mechanisms of Endogenous Neuroprotective Effects of Astrocytes in Brain Injury

PubMed Central

2018-01-01

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

Acoustic Processing of Temporally Modulated Sounds in Infants: Evidence from a Combined Near-Infrared Spectroscopy and EEG Study

PubMed Central

Telkemeyer, Silke; Rossi, Sonja; Nierhaus, Till; Steinbrink, Jens; Obrig, Hellmuth; Wartenburger, Isabell

2010-01-01

Speech perception requires rapid extraction of the linguistic content from the acoustic signal. The ability to efficiently process rapid changes in auditory information is important for decoding speech and thereby crucial during language acquisition. Investigating functional networks of speech perception in infancy might elucidate neuronal ensembles supporting perceptual abilities that gate language acquisition. Interhemispheric specializations for language have been demonstrated in infants. How these asymmetries are shaped by basic temporal acoustic properties is under debate. We recently provided evidence that newborns process non-linguistic sounds sharing temporal features with language in a differential and lateralized fashion. The present study used the same material while measuring brain responses of 6 and 3 month old infants using simultaneous recordings of electroencephalography (EEG) and near-infrared spectroscopy (NIRS). NIRS reveals that the lateralization observed in newborns remains constant over the first months of life. While fast acoustic modulations elicit bilateral neuronal activations, slow modulations lead to right-lateralized responses. Additionally, auditory-evoked potentials and oscillatory EEG responses show differential responses for fast and slow modulations indicating a sensitivity for temporal acoustic variations. Oscillatory responses reveal an effect of development, that is, 6 but not 3 month old infants show stronger theta-band desynchronization for slowly modulated sounds. Whether this developmental effect is due to increasing fine-grained perception for spectrotemporal sounds in general remains speculative. Our findings support the notion that a more general specialization for acoustic properties can be considered the basis for lateralization of speech perception. The results show that concurrent assessment of vascular based imaging and electrophysiological responses have great potential in the research on language acquisition. PMID:21716574

Empathic Brain Responses in Insula Are Modulated by Levels of Alexithymia but Not Autism

ERIC Educational Resources Information Center

Bird, Geoffrey; Silani, Giorgia; Brindley, Rachel; White, Sarah; Frith, Uta; Singer, Tania

2010-01-01

Difficulties in social cognition are well recognized in individuals with autism spectrum conditions (henceforth "autism"). Here we focus on one crucial aspect of social cognition: the ability to empathize with the feelings of another. In contrast to theory of mind, a capacity that has often been observed to be impaired in individuals with autism,…

Modulators of IgG penetration through the blood-brain barrier: Implications for Alzheimer's disease immunotherapy.

PubMed

Finke, John M; Banks, William A

2017-01-01

This review serves to highlight approaches that may improve the access of antibody drugs to regions of the brain affected by Alzheimer's Disease. While previous antibody drugs have been unsuccessful in treating Alzheimer's disease, recent work demonstrates that Alzheimer's pathology can be modified if these drugs can penetrate the brain parenchyma with greater efficacy. Research in antibody blood-brain barrier drug delivery predominantly follows one of three distinct directions: (1) enhancing influx with reduced antibody size, addition of Trojan horse modules, or blood-brain barrier disruption; (2) modulating trancytotic equilibrium and/or kinetics of the neonatal Fc Receptor; and (3) manipulation of antibody glycan carbohydrate composition. In addition to these topics, recent studies are discussed that reveal a role of glycan sialic acid in suppressing antibody efflux from the brain.

Vedolizumab: A New Opponent in the Battle Against Crohn's Disease and Ulcerative Colitis.

PubMed

Poulakos, Mara; Machin, Jade D; Pauly, Julienne; Grace, Yasmin

2016-10-01

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders affecting the gastrointestinal (GI) tract that encompass Crohn's disease (CD) and ulcerative colitis (UC). In these disease states, epithelial damage of the intestinal mucosa is evident due to increased lymphocyte trafficking to the area, which affects the normal intestinal barrier function. Currently available pharmacotherapy can be limited in terms of efficacy and associated toxicities. Newer agents have emerged, including the monoclonal antibody natalizumab, which antagonizes integrin, an important component within the inflammation cascade. Natalizumab works by modulating both the GI and brain biologic responses and as a result there is risk of the opportunistic infection known as progressive multifocal leukoencephalopathy (PML), putting patients at risk for severe disability and death. Vedolizumab, another integrin inhibitor, is selective for modulating the gut biologic response but not the brain, consequently decreasing the risk for PML. To generate information regarding the role of vedolizumab in the treatment of IBD, a literature search was conducted, yielding 7 phase I to III clinical trials. This article serves as a summary of efficacy, safety, and other relevant information from clinical studies to explore the role of vedolizumab in the treatment of CD and UC. © The Author(s) 2015.

Oxytocin attenuates neural reactivity to masked threat cues from the eyes.

PubMed

Kanat, Manuela; Heinrichs, Markus; Schwarzwald, Ralf; Domes, Gregor

2015-01-01

The neuropeptide oxytocin has recently been shown to modulate covert attention shifts to emotional face cues and to improve discrimination of masked facial emotions. These results suggest that oxytocin modulates facial emotion processing at early perceptual stages prior to full evaluation of the emotional expression. Here, we used functional magnetic resonance imaging to examine whether oxytocin alters neural responses to backwardly masked angry and happy faces while controlling for attention to the eye vs the mouth region. Intranasal oxytocin administration reduced amygdala reactivity to masked emotions when attending to salient facial features, ie, the eyes of angry faces and the mouth of happy faces. In addition, oxytocin decreased neural responses within the fusiform gyrus and brain stem areas, as well as functional coupling between the amygdala and the fusiform gyrus specifically for threat cues from the eyes. Effects of oxytocin on brain activity were not attributable to differences in behavioral performance, as oxytocin had no impact on mere emotion detection. Our results suggest that oxytocin attenuates neural correlates of early arousal by threat signals from the eye region. As reduced threat sensitivity may increase the likelihood of engaging in social interactions, our findings may have important implications for clinical states of social anxiety.

Electrocortical amplification for emotionally arousing natural scenes: The contribution of luminance and chromatic visual channels

PubMed Central

Miskovic, Vladimir; Martinovic, Jasna; Wieser, Matthias M.; Petro, Nathan M.; Bradley, Margaret M.; Keil, Andreas

2015-01-01

Emotionally arousing scenes readily capture visual attention, prompting amplified neural activity in sensory regions of the brain. The physical stimulus features and related information channels in the human visual system that contribute to this modulation, however, are not known. Here, we manipulated low-level physical parameters of complex scenes varying in hedonic valence and emotional arousal in order to target the relative contributions of luminance based versus chromatic visual channels to emotional perception. Stimulus-evoked brain electrical activity was measured during picture viewing and used to quantify neural responses sensitive to lower-tier visual cortical involvement (steady-state visual evoked potentials) as well as the late positive potential, reflecting a more distributed cortical event. Results showed that the enhancement for emotional content was stimulus-selective when examining the steady-state segments of the evoked visual potentials. Response amplification was present only for low spatial frequency, grayscale stimuli, and not for high spatial frequency, red/green stimuli. In contrast, the late positive potential was modulated by emotion regardless of the scene’s physical properties. Our findings are discussed in relation to neurophysiologically plausible constraints operating at distinct stages of the cortical processing stream. PMID:25640949

The primate amygdala represents the positive and negative value of visual stimuli during learning

PubMed Central

Paton, Joseph J.; Belova, Marina A.; Morrison, Sara E.; Salzman, C. Daniel

2008-01-01

Visual stimuli can acquire positive or negative value through their association with rewards and punishments, a process called reinforcement learning. Although we now know a great deal about how the brain analyses visual information, we know little about how visual representations become linked with values. To study this process, we turned to the amygdala, a brain structure implicated in reinforcement learning1–5. We recorded the activity of individual amygdala neurons in monkeys while abstract images acquired either positive or negative value through conditioning. After monkeys had learned the initial associations, we reversed image value assignments. We examined neural responses in relation to these reversals in order to estimate the relative contribution to neural activity of the sensory properties of images and their conditioned values. Here we show that changes in the values of images modulate neural activity, and that this modulation occurs rapidly enough to account for, and correlates with, monkeys’ learning. Furthermore, distinct populations of neurons encode the positive and negative values of visual stimuli. Behavioural and physiological responses to visual stimuli may therefore be based in part on the plastic representation of value provided by the amygdala. PMID:16482160

Emotional context enhances auditory novelty processing in superior temporal gyrus.

PubMed

Domínguez-Borràs, Judith; Trautmann, Sina-Alexa; Erhard, Peter; Fehr, Thorsten; Herrmann, Manfred; Escera, Carles

2009-07-01

Visualizing emotionally loaded pictures intensifies peripheral reflexes toward sudden auditory stimuli, suggesting that the emotional context may potentiate responses elicited by novel events in the acoustic environment. However, psychophysiological results have reported that attentional resources available to sounds become depleted, as attention allocation to emotional pictures increases. These findings have raised the challenging question of whether an emotional context actually enhances or attenuates auditory novelty processing at a central level in the brain. To solve this issue, we used functional magnetic resonance imaging to first identify brain activations induced by novel sounds (NOV) when participants made a color decision on visual stimuli containing both negative (NEG) and neutral (NEU) facial expressions. We then measured modulation of these auditory responses by the emotional load of the task. Contrary to what was assumed, activation induced by NOV in superior temporal gyrus (STG) was enhanced when subjects responded to faces with a NEG emotional expression compared with NEU ones. Accordingly, NOV yielded stronger behavioral disruption on subjects' performance in the NEG context. These results demonstrate that the emotional context modulates the excitability of auditory and possibly multimodal novelty cerebral regions, enhancing acoustic novelty processing in a potentially harming environment.

Electrocortical amplification for emotionally arousing natural scenes: the contribution of luminance and chromatic visual channels.

PubMed

Miskovic, Vladimir; Martinovic, Jasna; Wieser, Matthias J; Petro, Nathan M; Bradley, Margaret M; Keil, Andreas

2015-03-01

Emotionally arousing scenes readily capture visual attention, prompting amplified neural activity in sensory regions of the brain. The physical stimulus features and related information channels in the human visual system that contribute to this modulation, however, are not known. Here, we manipulated low-level physical parameters of complex scenes varying in hedonic valence and emotional arousal in order to target the relative contributions of luminance based versus chromatic visual channels to emotional perception. Stimulus-evoked brain electrical activity was measured during picture viewing and used to quantify neural responses sensitive to lower-tier visual cortical involvement (steady-state visual evoked potentials) as well as the late positive potential, reflecting a more distributed cortical event. Results showed that the enhancement for emotional content was stimulus-selective when examining the steady-state segments of the evoked visual potentials. Response amplification was present only for low spatial frequency, grayscale stimuli, and not for high spatial frequency, red/green stimuli. In contrast, the late positive potential was modulated by emotion regardless of the scene's physical properties. Our findings are discussed in relation to neurophysiologically plausible constraints operating at distinct stages of the cortical processing stream. Copyright © 2015 Elsevier B.V. All rights reserved.

Modulation of A-type potassium channels by a family of calcium sensors.

PubMed

An, W F; Bowlby, M R; Betty, M; Cao, J; Ling, H P; Mendoza, G; Hinson, J W; Mattsson, K I; Strassle, B W; Trimmer, J S; Rhodes, K J

2000-02-03

In the brain and heart, rapidly inactivating (A-type) voltage-gated potassium (Kv) currents operate at subthreshold membrane potentials to control the excitability of neurons and cardiac myocytes. Although pore-forming alpha-subunits of the Kv4, or Shal-related, channel family form A-type currents in heterologous cells, these differ significantly from native A-type currents. Here we describe three Kv channel-interacting proteins (KChIPs) that bind to the cytoplasmic amino termini of Kv4 alpha-subunits. We find that expression of KChIP and Kv4 together reconstitutes several features of native A-type currents by modulating the density, inactivation kinetics and rate of recovery from inactivation of Kv4 channels in heterologous cells. All three KChIPs co-localize and co-immunoprecipitate with brain Kv4 alpha-subunits, and are thus integral components of native Kv4 channel complexes. The KChIPs have four EF-hand-like domains and bind calcium ions. As the activity and density of neuronal A-type currents tightly control responses to excitatory synaptic inputs, these KChIPs may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium.

Repetition suppression of faces is modulated by emotion

NASA Astrophysics Data System (ADS)

Ishai, Alumit; Pessoa, Luiz; Bikle, Philip C.; Ungerleider, Leslie G.

2004-06-01

Single-unit recordings and functional brain imaging studies have shown reduced neural responses to repeated stimuli in the visual cortex. By using event-related functional MRI, we compared the activation evoked by repetitions of neutral and fearful faces, which were either task relevant (targets) or irrelevant (distracters). We found that within the inferior occipital gyri, lateral fusiform gyri, superior temporal sulci, amygdala, and the inferior frontal gyri/insula, targets evoked stronger responses than distracters and their repetition was associated with significantly reduced responses. Repetition suppression, as manifested by the difference in response amplitude between the first and third repetitions of a target, was stronger for fearful than neutral faces. Distracter faces, regardless of their repetition or valence, evoked negligible activation, indicating top-down attenuation of behaviorally irrelevant stimuli. Our findings demonstrate a three-way interaction between emotional valence, repetition, and task relevance and suggest that repetition suppression is influenced by high-level cognitive processes in the human brain. face perception | functional MRI

Genetic Differences in the Immediate Transcriptome Response to Stress Predict Risk-Related Brain Function and Psychiatric Disorders

PubMed Central

Arloth, Janine; Bogdan, Ryan; Weber, Peter; Frishman, Goar; Menke, Andreas; Wagner, Klaus V.; Balsevich, Georgia; Schmidt, Mathias V.; Karbalai, Nazanin; Czamara, Darina; Altmann, Andre; Trümbach, Dietrich; Wurst, Wolfgang; Mehta, Divya; Uhr, Manfred; Klengel, Torsten; Erhardt, Angelika; Carey, Caitlin E.; Conley, Emily Drabant; Ripke, Stephan; Wray, Naomi R.; Lewis, Cathryn M.; Hamilton, Steven P.; Weissman, Myrna M.; Breen, Gerome; Byrne, Enda M.; Blackwood, Douglas H.R.; Boomsma, Dorret I.; Cichon, Sven; Heath, Andrew C.; Holsboer, Florian; Lucae, Susanne; Madden, Pamela A.F.; Martin, Nicholas G.; McGuffin, Peter; Muglia, Pierandrea; Noethen, Markus M.; Penninx, Brenda P.; Pergadia, Michele L.; Potash, James B.; Rietschel, Marcella; Lin, Danyu; Müller-Myhsok, Bertram; Shi, Jianxin; Steinberg, Stacy; Grabe, Hans J.; Lichtenstein, Paul; Magnusson, Patrik; Perlis, Roy H.; Preisig, Martin; Smoller, Jordan W.; Stefansson, Kari; Uher, Rudolf; Kutalik, Zoltan; Tansey, Katherine E.; Teumer, Alexander; Viktorin, Alexander; Barnes, Michael R.; Bettecken, Thomas; Binder, Elisabeth B.; Breuer, René; Castro, Victor M.; Churchill, Susanne E.; Coryell, William H.; Craddock, Nick; Craig, Ian W.; Czamara, Darina; De Geus, Eco J.; Degenhardt, Franziska; Farmer, Anne E.; Fava, Maurizio; Frank, Josef; Gainer, Vivian S.; Gallagher, Patience J.; Gordon, Scott D.; Goryachev, Sergey; Gross, Magdalena; Guipponi, Michel; Henders, Anjali K.; Herms, Stefan; Hickie, Ian B.; Hoefels, Susanne; Hoogendijk, Witte; Hottenga, Jouke Jan; Iosifescu, Dan V.; Ising, Marcus; Jones, Ian; Jones, Lisa; Jung-Ying, Tzeng; Knowles, James A.; Kohane, Isaac S.; Kohli, Martin A.; Korszun, Ania; Landen, Mikael; Lawson, William B.; Lewis, Glyn; MacIntyre, Donald; Maier, Wolfgang; Mattheisen, Manuel; McGrath, Patrick J.; McIntosh, Andrew; McLean, Alan; Middeldorp, Christel M.; Middleton, Lefkos; Montgomery, Grant M.; Murphy, Shawn N.; Nauck, Matthias; Nolen, Willem A.; Nyholt, Dale R.; O’Donovan, Michael; Oskarsson, Högni; Pedersen, Nancy; Scheftner, William A.; Schulz, Andrea; Schulze, Thomas G.; Shyn, Stanley I.; Sigurdsson, Engilbert; Slager, Susan L.; Smit, Johannes H.; Stefansson, Hreinn; Steffens, Michael; Thorgeirsson, Thorgeir; Tozzi, Federica; Treutlein, Jens; Uhr, Manfred; van den Oord, Edwin J.C.G.; Van Grootheest, Gerard; Völzke, Henry; Weilburg, Jeffrey B.; Willemsen, Gonneke; Zitman, Frans G.; Neale, Benjamin; Daly, Mark; Levinson, Douglas F.; Sullivan, Patrick F.; Ruepp, Andreas; Müller-Myhsok, Bertram; Hariri, Ahmad R.; Binder, Elisabeth B.

2015-01-01

Summary Depression risk is exacerbated by genetic factors and stress exposure; however, the biological mechanisms through which these factors interact to confer depression risk are poorly understood. One putative biological mechanism implicates variability in the ability of cortisol, released in response to stress, to trigger a cascade of adaptive genomic and non-genomic processes through glucocorticoid receptor (GR) activation. Here, we demonstrate that common genetic variants in long-range enhancer elements modulate the immediate transcriptional response to GR activation in human blood cells. These functional genetic variants increase risk for depression and co-heritable psychiatric disorders. Moreover, these risk variants are associated with inappropriate amygdala reactivity, a transdiagnostic psychiatric endophenotype and an important stress hormone response trigger. Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain. Video Abstract PMID:26050039

Brain oscillations and BIS/BAS (behavioral inhibition/activation system) effects on processing masked emotional cues. ERS/ERD and coherence measures of alpha band.

PubMed

Balconi, Michela; Mazza, Guido

2009-11-01

Alpha brain oscillation modulation was analyzed in response to masked emotional facial expressions. In addition, behavioural activation (BAS) and behavioural inhibition systems (BIS) were considered as an explicative factor to verify the effect of motivational significance on cortical activity. Nineteen subjects were submitted to an ample range of facial expressions of emotions (anger, fear, surprise, disgust, happiness, sadness, and neutral). The results demonstrated that anterior frontal sites were more active than central and posterior sites in response to facial stimuli. Moreover, right-side responses varied as a function of emotional types, with an increased right-frontal activity for negative emotions. Finally, whereas higher BIS subjects generated a more right hemisphere activation for some negative emotions (such as fear, anger, and surprise), Reward-BAS subjects were more responsive to positive emotion (happiness) within the left hemisphere. Valence and potential threatening power of facial expressions were considered to elucidate these cortical differences.

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

PubMed Central

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

2011-01-01

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

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

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

SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

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

Hossain, S; Hildebrand, K; Ahmad, S

Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targetsmore » were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.« less

Host-Toxoplasma gondii Coadaptation Leads to Fine Tuning of the Immune Response.

PubMed

Brasil, Thaís Rigueti; Freire-de-Lima, Celio Geraldo; Morrot, Alexandre; Vetö Arnholdt, Andrea Cristina

2017-01-01

Toxoplasma gondii has successfully developed strategies to evade host's immune response and reach immune privileged sites, which remains in a controlled environment inside quiescent tissue cysts. In this review, we will approach several known mechanisms used by the parasite to modulate mainly the murine immune system at its favor. In what follows, we review recent findings revealing interference of host's cell autonomous immunity and cell signaling, gene expression, apoptosis, and production of microbicide molecules such as nitric oxide and oxygen reactive species during parasite infection. Modulation of host's metalloproteinases of extracellular matrix is also discussed. These immune evasion strategies are determinant to parasite dissemination throughout the host taking advantage of cells from the immune system to reach brain and retina, crossing crucial hosts' barriers.

Host-Toxoplasma gondii Coadaptation Leads to Fine Tuning of the Immune Response

PubMed Central

Brasil, Thaís Rigueti; Freire-de-Lima, Celio Geraldo; Morrot, Alexandre; Vetö Arnholdt, Andrea Cristina

2017-01-01

Toxoplasma gondii has successfully developed strategies to evade host’s immune response and reach immune privileged sites, which remains in a controlled environment inside quiescent tissue cysts. In this review, we will approach several known mechanisms used by the parasite to modulate mainly the murine immune system at its favor. In what follows, we review recent findings revealing interference of host’s cell autonomous immunity and cell signaling, gene expression, apoptosis, and production of microbicide molecules such as nitric oxide and oxygen reactive species during parasite infection. Modulation of host’s metalloproteinases of extracellular matrix is also discussed. These immune evasion strategies are determinant to parasite dissemination throughout the host taking advantage of cells from the immune system to reach brain and retina, crossing crucial hosts’ barriers. PMID:28955329

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.

Real-time fMRI and its application to neurofeedback.

PubMed

Weiskopf, Nikolaus

2012-08-15

Real-time fMRI (rtfMRI) allows immediate access to experimental results by analyzing data as fast as they are acquired. It was devised soon after the inception of fMRI and has undergone a rapid development since then. The availability of results during the ongoing experiment facilitates a variety of applications such as quality assurance or fast functional localization. RtfMRI can also be used as a brain-computer interface (BCI) with high spatial resolution and whole-brain coverage, overcoming limitations of EEG based BCIs. This review will focus on the application of rtfMRI BCIs to neurofeedback, i.e., the online feedback of the blood oxygen level dependent (BOLD) response. I will motivate its development and place its beginnings into the contemporary scientific context by providing an account of our early work at the University of Tübingen, followed by a review of the accomplishments and the current state of rtfMRI neurofeedback. RtfMRI neurofeedback has been used to train self-regulation of the local BOLD response in various different brain areas and to study consequential behavioral effects. Behavioral effects such as modulation of pain, reaction time, linguistic or emotional processing have been shown in healthy and/or patient populations. RtfMRI neurofeedback presents a new paradigm for studying the relation between brain behavior and physiology, because the latter can be regarded as the independent variable (unlike in conventional neuroimaging studies where behavior is the independent variable). The initial results in patient populations improving pain, tinnitus, depression or modulating perception in schizophrenia are encouraging and merit further controlled clinical studies. Copyright © 2011 Elsevier Inc. All rights reserved.

Brain Network Modularity Predicts Exercise-Related Executive Function Gains in Older Adults

PubMed Central

Baniqued, Pauline L.; Gallen, Courtney L.; Voss, Michelle W.; Burzynska, Agnieszka Z.; Wong, Chelsea N.; Cooke, Gillian E.; Duffy, Kristin; Fanning, Jason; Ehlers, Diane K.; Salerno, Elizabeth A.; Aguiñaga, Susan; McAuley, Edward; Kramer, Arthur F.; D'Esposito, Mark

2018-01-01

Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules. Previous work has shown that higher modularity predicts greater improvements after cognitive training in patients with traumatic brain injury and in healthy older and young adults. It is not known, however, whether modularity can also predict cognitive gains after a physical exercise intervention. Here, we quantified modularity in older adults (N = 128, mean age = 64.74) who underwent one of the following interventions for 6 months (NCT01472744 on ClinicalTrials.gov): (1) aerobic exercise in the form of brisk walking (Walk), (2) aerobic exercise in the form of brisk walking plus nutritional supplement (Walk+), (3) stretching, strengthening and stability (SSS), or (4) dance instruction. After the intervention, the Walk, Walk+ and SSS groups showed gains in cardiorespiratory fitness (CRF), with larger effects in both walking groups compared to the SSS and Dance groups. The Walk, Walk+ and SSS groups also improved in executive function (EF) as measured by reasoning, working memory, and task-switching tests. In the Walk, Walk+, and SSS groups that improved in EF, higher baseline modularity was positively related to EF gains, even after controlling for age, in-scanner motion and baseline EF. No relationship between modularity and EF gains was observed in the Dance group, which did not show training-related gains in CRF or EF control. These results are consistent with previous studies demonstrating that individuals with a more modular brain network organization are more responsive to cognitive training. These findings suggest that the predictive power of modularity may be generalizable across interventions aimed to enhance aspects of cognition and that, especially in low-performing individuals, global network properties can capture individual differences in neuroplasticity. PMID:29354050

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

PubMed Central

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

2015-01-01

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

Temporal and spatial localization of prediction-error signals in the visual brain.

PubMed

Johnston, Patrick; Robinson, Jonathan; Kokkinakis, Athanasios; Ridgeway, Samuel; Simpson, Michael; Johnson, Sam; Kaufman, Jordy; Young, Andrew W

2017-04-01

It has been suggested that the brain pre-empts changes in the environment through generating predictions, although real-time electrophysiological evidence of prediction violations in the domain of visual perception remain elusive. In a series of experiments we showed participants sequences of images that followed a predictable implied sequence or whose final image violated the implied sequence. Through careful design we were able to use the same final image transitions across predictable and unpredictable conditions, ensuring that any differences in neural responses were due only to preceding context and not to the images themselves. EEG and MEG recordings showed that early (N170) and mid-latency (N300) visual evoked potentials were robustly modulated by images that violated the implied sequence across a range of types of image change (expression deformations, rigid-rotations and visual field location). This modulation occurred irrespective of stimulus object category. Although the stimuli were static images, MEG source reconstruction of the early latency signal (N/M170) localized expectancy violation signals to brain areas associated with motion perception. Our findings suggest that the N/M170 can index mismatches between predicted and actual visual inputs in a system that predicts trajectories based on ongoing context. More generally we suggest that the N/M170 may reflect a "family" of brain signals generated across widespread regions of the visual brain indexing the resolution of top-down influences and incoming sensory data. This has important implications for understanding the N/M170 and investigating how the brain represents context to generate perceptual predictions. Copyright © 2017 Elsevier B.V. All rights reserved.

Diurnal cortisol amplitude and fronto-limbic activity in response to stressful stimuli

PubMed Central

Cunningham-Bussel, Amy C.; Root, James C.; Butler, Tracy; Tuescher, Oliver; Pan, Hong; Epstein, Jane; Weisholtz, Daniel S.; Pavony, Michelle; Silverman, Michael E.; Goldstein, Martin S.; Altemus, Margaret; Cloitre, Marylene; LeDoux, Joseph; McEwen, Bruce; Stern, Emily; Silbersweig, David

2014-01-01

Summary The development and exacerbation of many psychiatric and neurologic conditions are associated with dysregulation of the hypothalamic pituitary adrenal (HPA) axis as measured by aberrant levels of cortisol secretion. Here we report on the relationship between the amplitude of diurnal cortisol secretion, measured across 3 typical days in 18 healthy individuals, and blood oxygen level dependant (BOLD) response in limbic fear/stress circuits, elicited by in-scanner presentation of emotionally negative stimuli, specifically, images of the World Trade Center (WTC) attack. Results indicate that subjects who secrete a greater amplitude of cortisol diurnally demonstrate less brain activation in limbic regions, including the amygdala and hippocampus/parahippocampus, and hypothalamus during exposure to traumatic WTC-related images. Such initial findings can begin to link our understanding, in humans, of the relationship between the diurnal amplitude of a hormone integral to the stress response, and those neuroanatomical regions that are implicated as both modulating and being modulated by that response. PMID:19135805

Dynamic modulation of decision biases by brainstem arousal systems.

PubMed

de Gee, Jan Willem; Colizoli, Olympia; Kloosterman, Niels A; Knapen, Tomas; Nieuwenhuis, Sander; Donner, Tobias H

2017-04-11

Decision-makers often arrive at different choices when faced with repeated presentations of the same evidence. Variability of behavior is commonly attributed to noise in the brain's decision-making machinery. We hypothesized that phasic responses of brainstem arousal systems are a significant source of this variability. We tracked pupil responses (a proxy of phasic arousal) during sensory-motor decisions in humans, across different sensory modalities and task protocols. Large pupil responses generally predicted a reduction in decision bias. Using fMRI, we showed that the pupil-linked bias reduction was (i) accompanied by a modulation of choice-encoding pattern signals in parietal and prefrontal cortex and (ii) predicted by phasic, pupil-linked responses of a number of neuromodulatory brainstem centers involved in the control of cortical arousal state, including the noradrenergic locus coeruleus. We conclude that phasic arousal suppresses decision bias on a trial-by-trial basis, thus accounting for a significant component of the variability of choice behavior.

Transferrin Receptor 2 Dependent Alterations of Brain Iron Metabolism Affect Anxiety Circuits in the Mouse

PubMed Central

Pellegrino, Rosa Maria; Boda, Enrica; Montarolo, Francesca; Boero, Martina; Mezzanotte, Mariarosa; Saglio, Giuseppe; Buffo, Annalisa; Roetto, Antonella

2016-01-01

The Transferrin Receptor 2 (Tfr2) modulates systemic iron metabolism through the regulation of iron regulator Hepcidin (Hepc) and Tfr2 inactivation causes systemic iron overload. Based on data demonstrating Tfr2 expression in brain, we analysed Tfr2-KO mice in order to examine the molecular, histological and behavioural consequences of Tfr2 silencing in this tissue. Tfr2 abrogation caused an accumulation of iron in specific districts in the nervous tissue that was not accompanied by a brain Hepc response. Moreover, Tfr2-KO mice presented a selective overactivation of neurons in the limbic circuit and the emergence of an anxious-like behaviour. Furthermore, microglial cells showed a particular sensitivity to iron perturbation. We conclude that Tfr2 is a key regulator of brain iron homeostasis and propose a role for Tfr2 alpha in the regulation of anxiety circuits. PMID:27477597

Rapid control of male typical behaviors by brain-derived estrogens

PubMed Central

Cornil, Charlotte A.; Ball, Gregory F.; Balthazart, Jacques

2012-01-01

Beside their genomic mode of action, estrogens also activate a variety of cellular signaling pathways through non-genomic mechanisms. Until recently, little was known regarding the functional significance of such actions in males and the mechanism that control local estrogen concentration with a spatial and time resolution compatible with these non-genomic actions had rarely been examined. Here, we review evidence that estrogens rapidly modulate a variety of behaviors in male vertebrates. Then, we present in vitro work supporting the existence of a control mechanism of local brain estrogen synthesis by aromatase along with in vivo evidence that rapid changes in aromatase activity also occur in a region-specific manner in response to changes in the social or environmental context. Finally, we suggest that the brain estrogen provision may also play a significant role in females. Together these data bolster the hypothesis that brain-derived estrogens should be considered as neuromodulators. PMID:22983088

The brain's dress code: How The Dress allows to decode the neuronal pathway of an optical illusion.

PubMed

Schlaffke, Lara; Golisch, Anne; Haag, Lauren M; Lenz, Melanie; Heba, Stefanie; Lissek, Silke; Schmidt-Wilcke, Tobias; Eysel, Ulf T; Tegenthoff, Martin

2015-12-01

Optical illusions have broadened our understanding of the brain's role in visual perception. A modern day optical illusion emerged from a posted photo of a striped dress, which some perceived as white and gold and others as blue and black. Here we show, using functional magnetic resonance imaging (fMRI), that those who perceive The Dress as white/gold have higher activation in response to the image of The Dress in brain regions critically involved in higher cognition (frontal and parietal brain areas). These results are consistent with theories of top-down modulation and present a neural signature associated with the differences in perceiving The Dress as white/gold or blue/black. Furthermore the results support recent psychophysiological data on this phenomenon and provide a fundamental building block to study interindividual differences in visual processing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Targeted, noninvasive blockade of cortical neuronal activity

NASA Astrophysics Data System (ADS)

McDannold, Nathan; Zhang, Yongzhi; Power, Chanikarn; Arvanitis, Costas D.; Vykhodtseva, Natalia; Livingstone, Margaret

2015-11-01

Here we describe a novel method to noninvasively modulate targeted brain areas through the temporary disruption of the blood-brain barrier (BBB) via focused ultrasound, enabling focal delivery of a neuroactive substance. Ultrasound was used to locally disrupt the BBB in rat somatosensory cortex, and intravenous administration of GABA then produced a dose-dependent suppression of somatosensory-evoked potentials in response to electrical stimulation of the sciatic nerve. No suppression was observed 1-5 days afterwards or in control animals where the BBB was not disrupted. This method has several advantages over existing techniques: it is noninvasive; it is repeatable via additional GABA injections; multiple brain regions can be affected simultaneously; suppression magnitude can be titrated by GABA dose; and the method can be used with freely behaving subjects. We anticipate that the application of neuroactive substances in this way will be a useful tool for noninvasively mapping brain function, and potentially for surgical planning or novel therapies.

Oxytocin modulates the racial bias in neural responses to others' suffering.

PubMed

Sheng, Feng; Liu, Yi; Zhou, Bin; Zhou, Wen; Han, Shihui

2013-02-01

The intergroup relationship between a perceiver and a target person influences empathic neural responses to others' suffering, which are increased for racial in-group members compared to out-group members. The current study investigated whether oxytocin (OT), a neuropeptide that has been linked to empathic concern and in-group favoritism, contributes to the racial bias in empathic neural responses. Event-related brain potentials were recorded in Chinese male adults during race judgments on Asian and Caucasian faces expressing pain or showing a neutral expression after intranasal self-administration of OT or placebo. A fronto-central positive activity at 128-188 ms (P2) was of larger amplitude in response to the pain expressions compared with the neutral expressions of racial in-group members but not of racial out-group members. OT treatment increased this racial in-group bias in neural responses and resulted in its correlation with a positive implicit attitude toward racial in-group members. Our findings suggest that OT interacts with the intergroup relationship to modulate empathic neural responses to others' suffering. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

Individualized model predicts brain current flow during transcranial direct-current stimulation treatment in responsive stroke patient.

PubMed

Datta, Abhishek; Baker, Julie M; Bikson, Marom; Fridriksson, Julius

2011-07-01

Although numerous published reports have demonstrated the beneficial effects of transcranial direct-current stimulation (tDCS) on task performance, fundamental questions remain regarding the optimal electrode configuration on the scalp. Moreover, it is expected that lesioned brain tissue will influence current flow and should therefore be considered (and perhaps leveraged) in the design of individualized tDCS therapies for stroke. The current report demonstrates how different electrode configurations influence the flow of electrical current through brain tissue in a patient who responded positively to a tDCS treatment targeting aphasia. The patient, a 60-year-old man, sustained a left hemisphere ischemic stroke (lesion size = 87.42 mL) 64 months before his participation. In this study, we present results from the first high-resolution (1 mm(3)) model of tDCS in a brain with considerable stroke-related damage; the model was individualized for the patient who received anodal tDCS to his left frontal cortex with the reference cathode electrode placed on his right shoulder. We modeled the resulting brain current flow and also considered three additional reference electrode positions: right mastoid, right orbitofrontal cortex, and a "mirror" configuration with the anode over the undamaged right cortex. Our results demonstrate the profound effect of lesioned tissue on resulting current flow and the ability to modulate current pattern through the brain, including perilesional regions, through electrode montage design. The complexity of brain current flow modulation by detailed normal and pathologic anatomy suggest: (1) That computational models are critical for the rational interpretation and design of individualized tDCS stroke-therapy; and (2) These models must accurately reproduce head anatomy as shown here. Copyright © 2011 Elsevier Inc. All rights reserved.

Testicular atrophy and reproductive quiescence in photorefractory and scotosensitive quail: Involvement of hypothalamic deep brain photoreceptors and GnRH-GnIH system.

PubMed

Banerjee, Somanshu; Chaturvedi, Chandra Mohini

2017-10-01

Birds time their daily and seasonal activities in synchronization with circadian and annual periodicities in the environment, which is mainly provided by changes in photoperiod/day length conditions. Photoperiod appears to act at the level of eye, pineal and encephalic/deep brain photoperception and thus entrain the hypothalamic clock as well as reproductive circuitry in different avian species. In this article our focus of study is to elucidate out the underlying molecular mechanism of modulation of the hypothalamic reproductive circuitry following the photoperception through the hypothalamic photoreceptor cells and the subsequent alteration in the reproductive responses in quail, kept under different simulated photoperiodic conditions. Present study investigated the different simulated photoperiodic conditions induced hypothalamic DBP-GnRH-GnIH system mediated translation of photoperiodic information and subsequent exhibition of differential photosexual responses (scoto-/photo-sensitivity and refractoriness) in Japanese quail, Coturnix coturnix japonica. Paired testes weight and paired testicular volume increased 15.9 and 22.6-fold respectively in scotorefractory quail compare to that of scotosensitive phase and 12.8 and 24.3-fold in photosensitive quail compare to that of photorefractory phase. The pineal/eye melatonin (through melatonin receptor subtype Mel 1c R) and hypothalamic deep brain photoreceptor (DBPs) cells directly modulate the hypothalamic GnRH-I/II and GnIH system and thus exhibit testicular stimulation or regression in response to different photoperiodic conditions (PS, PR, SS and SR). The hypothalamic alteration of DBP(s) and GnRH-GnIH system thus may induce the testicular stimulation in PS and SR quail and testicular regression in SS and PR quail. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Haptic contents of a movie dynamically engage the spectator's sensorimotor cortex.

PubMed

Lankinen, Kaisu; Smeds, Eero; Tikka, Pia; Pihko, Elina; Hari, Riitta; Koskinen, Miika

2016-11-01

Observation of another person's actions and feelings activates brain areas that support similar functions in the observer, thereby facilitating inferences about the other's mental and bodily states. In real life, events eliciting this kind of vicarious brain activations are intermingled with other complex, ever-changing stimuli in the environment. One practical approach to study the neural underpinnings of real-life vicarious perception is to image brain activity during movie viewing. Here the goal was to find out how observed haptic events in a silent movie would affect the spectator's sensorimotor cortex. The functional state of the sensorimotor cortex was monitored by analyzing, in 16 healthy subjects, magnetoencephalographic (MEG) responses to tactile finger stimuli that were presented once per second throughout the session. Using canonical correlation analysis and spatial filtering, consistent single-trial responses across subjects were uncovered, and their waveform changes throughout the movie were quantified. The long-latency (85-175 ms) parts of the responses were modulated in concordance with the participants' average moment-by-moment ratings of own engagement in the haptic content of the movie (correlation r = 0.49; ratings collected after the MEG session). The results, obtained by using novel signal-analysis approaches, demonstrate that the functional state of the human sensorimotor cortex fluctuates in a fine-grained manner even during passive observation of temporally varying haptic events. Hum Brain Mapp 37:4061-4068, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Degradation of stored movement representations in the Parkinsonian brain and the impact of levodopa.

PubMed

D'Andrea, Jolyn N A; Haffenden, Angela M; Furtado, Sarah; Suchowersky, Oksana; Goodyear, Bradley G

2013-06-01

Parkinson's disease (PD) results from the depletion of dopamine and other neurotransmitters within the basal ganglia, and is typically characterized by motor impairment (e.g., bradykinesia) and difficulty initiating voluntary movements. Difficulty initiating a movement may result from a deficit in accessing or executing a stored representation of the movement, or having to create a new representation each time a movement is required. To date, it is unclear which may be responsible for movement initiation impairments observed in PD. In this study, we used functional magnetic resonance imaging and a task in which participants passively viewed familiar and unfamiliar graspable objects, with no confounding motor task component. Our results show that the brains of PD patients implicitly analyze familiar graspable objects as if the brain has little or no motor experience with the objects. This was observed as a lack of differential activity within brain regions associated with stored movement representations for familiar objects relative to unfamiliar objects, as well as significantly greater activity for familiar objects when off levodopa relative to on medication. Symptom severity modulated this activity difference within the basal ganglia. Levodopa appears to normalize brain activity, but its effect may be one of attenuation of brain hyperactivity within the basal ganglia network, which is responsible for controlling motor behavior and the integration of visuomotor information. Overall, this study demonstrates that difficulty initiating voluntary movements experienced by PD patients may be the result of degradation in stored representations responsible for the movement. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison of gene expression responses to hypoxia in viviparous (Xiphophorus) and oviparous (Oryzias) fishes using a medaka microarray.

PubMed

Boswell, Mikki G; Wells, Melissa C; Kirk, Lyndsey M; Ju, Zhenlin; Zhang, Ziping; Booth, Rachell E; Walter, Ronald B

2009-03-01

Gene expression profiling using DNA microarray technology is a useful tool for assessing gene transcript level responses after an organism is exposed to environmental stress. Herein, we detail results from studies using an 8 k medaka (Oryzias latipes) microarray to assess modulated gene expression patterns upon hypoxia exposure of the live-bearing aquaria fish, Xiphophorus maculatus. To assess the reproducibility and reliability of using the medaka array in cross-genus hybridization, a two-factor ANOVA analysis of gene expression was employed. The data show the tissue source of the RNA used for array hybridization contributed more to the observed response of modulated gene targets than did the species source of the RNA. In addition, hierarchical clustering via heat map analyses of groupings of tissues and species (Xiphophorus and medaka) suggests that hypoxia induced similar responses in the same tissues from these two diverse aquatic model organisms. Our Xiphophorus results indicate 206 brain, 37 liver, and 925 gill gene targets exhibit hypoxia induced expression changes. Analysis of the Xiphophorus data to determine those features exhibiting a significant (p<0.05)+/-3 fold change produced only two gene targets within brain tissue and 80 features within gill tissue. Of these 82 characterized features, 39 were identified via homology searching (cut-off E-value of 1 x 10(-5)) and placed into one or more biological process gene ontology groups. Among these 39 genes, metabolic energy changes and manipulation was the most affected biological pathway (13 genes).

Hemodynamic resuscitation with arginine vasopressin reduces lung injury after brain death in the transplant donor.

PubMed

Rostron, Anthony J; Avlonitis, Vassilios S; Cork, David M W; Grenade, Danielle S; Kirby, John A; Dark, John H

2008-02-27

The autonomic storm accompanying brain death leads to neurogenic pulmonary edema and triggers development of systemic and pulmonary inflammatory responses. Neurogenic vasoplegia exacerbates the pulmonary injury caused by brain death and primes the lung for ischemia reperfusion injury and primary graft dysfunction in the recipient. Donor resuscitation with norepinephrine ameliorates the inflammatory response to brain death, however norepinephrine has deleterious effects, particularly on the heart. We tested the hypothesis that arginine vasopressin is a suitable alternative to norepinephrine in managing the hypotensive brain dead donor. Brain death was induced in Wistar rats by intracranial balloon inflation. Pulmonary capillary leak was estimated using radioiodinated albumin. Development of pulmonary edema was assessed by measurement of wet and dry lung weights. Cell surface expression of CD11b/CD18 by neutrophils was determined using flow cytometry. Enzyme-linked immunosorbent assays were used to measure the levels of TNFalpha, IL-1beta, CINC-1, and CINC-3 in serum and bronchoalveolar lavage. Quantitative reverse-transcription polymerase chain reaction was used to determine the expression of cytokine mRNA (IL-1beta, CINC-1 and CINC-3) in lung tissue. There was a significant increase in pulmonary capillary permeability, wet/dry lung weight ratios, neutrophil integrin expression and pro-inflammatory cytokines in serum (TNFalpha, IL-1beta, CINC-1 and CINC-3), bronchoalveolar lavage (TNFalpha and IL-1beta) and lung tissue (IL-1beta and CINC-1) in braindead animals compared to controls. Correction of neurogenic hypotension with either arginine vasopressin or norepinephrine limits edema, reduces pulmonary capillary leak, and modulates systemic and pulmonary inflammatory responses to brain death. Arginine vasopressin and norepinephrine are equally effective in treating the hypotensive pulmonary donor in this rodent model.

Developmental lead exposure induces opposite effects on ethanol intake and locomotion in response to central vs. systemic cyanamide administration.

PubMed

Mattalloni, Mara Soledad; Deza-Ponzio, Romina; Albrecht, Paula Alejandra; Cancela, Liliana Marina; Virgolini, Miriam Beatriz

2017-02-01

Lead (Pb) is a developmental neurotoxicant that elicits differential responses to drugs of abuse. Particularly, ethanol consumption has been demonstrated to be increased as a consequence of environmental Pb exposure, with catalase (CAT) and brain acetaldehyde (ACD, the first metabolite of ethanol) playing a role. The present study sought to interfere with ethanol metabolism by inhibiting ALDH2 (mitochondrial aldehyde dehydrogenase) activity in both liver and brain from control and Pb-exposed rats as a strategy to accumulate ACD, a substance that plays a major role in the drug's reinforcing and/or aversive effects. To evaluate the impact on a 2-h chronic voluntary ethanol intake test, developmentally Pb-exposed and control rats were administered with cyanamide (CY, an ALDH inhibitor) either systemically or intracerebroventricularly (i.c.v.) on the last 4 sessions of the experiment. Furthermore, on the last session and after locomotor activity was assessed, all animals were sacrificed to obtain brain and liver samples for ALDH2 and CAT activity determination. Systemic CY administration reduced the elevated ethanol intake already reported in the Pb-exposed animals (but not in the controls) accompanied by liver (but not brain) ALDH2 inactivation. On the other hand, a 0.3 mg i.c.v. CY administration enhanced both ethanol intake and locomotor activity accompanied by brain ALDH2 inactivation in control animals, while an increase in ethanol consumption was also observed in the Pb-exposed group, although in the absence of brain ALDH2 blockade. No changes were observed in CAT activity as a consequence of CY administration. These results support the participation of liver and brain ACD in ethanol intake and locomotor activity, responses that are modulated by developmental Pb exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed

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

2018-03-19

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

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

PubMed

Rittschof, C C; Robinson, G E

2013-11-01

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

Episodic memory in aspects of large-scale brain networks

PubMed Central

Jeong, Woorim; Chung, Chun Kee; Kim, June Sic

2015-01-01

Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL) structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network (DMN). Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network (RSN). Altered patterns of functional connectivity (FC) among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment. PMID:26321939

SU-F-T-349: Dosimetric Comparison of Three Different Simultaneous Integrated Boost Irradiation Techniques for Multiple Brain Metastases: Intensity-Modulatedradiotherapy, Hybrid Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy

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

Lin, X; Sun, T; Yin, Y

Purpose: To study the dosimetric impact of intensity-modulated radiotherapy (IMRT), hybrid intensity-modulated radiotherapy (h-IMRT) and volumetric modulated arc therapy(VMAT) for whole-brain radiotherapy (WBRT) with simultaneous integrated boost in patients with multiple brain metastases. Methods: Ten patients with multiple brain metastases were included in this analysis. The prescribed dose was 45 Gy to the whole brain (PTVWBRT) and 55 Gy to individual brain metastases (PTVboost) delivered simultaneously in 25 fractions. Three treatment techniques were designed: the 7 equal spaced fields IMRT plan, hybrid IMRT plan and VMAT with two 358°arcs. In hybrid IMRT plan, two fields(90°and 270°) were planned to themore » whole brain. This was used as a base dose plan. Then 5 fields IMRT plan was optimized based on the two fields plan. The dose distribution in the target, the dose to the organs at risk and total MU in three techniques were compared. Results: For the target dose, conformity and homogeneity in PTV, no statistically differences were observed in the three techniques. For the maximum dose in bilateral lens and the mean dose in bilateral eyes, IMRT and h-IMRT plans showed the highest and lowest value respectively. No statistically significant differences were observed in the dose of optic nerve and brainstem. For the monitor units, IMRT and VMAT plans showed the highest and lowest value respectively. Conclusion: For WBRT with simultaneous integrated boost in patients with multiple brain metastases, hybrid IMRT could reduce the doses to lens and eyes. It is feasible for patients with brain metastases.« less

Cooling the injured brain: how does moderate hypothermia influence the pathophysiology of traumatic brain injury.

PubMed

Sahuquillo, Juan; Vilalta, Anna

2007-01-01

Neither any neuroprotective drug has been shown to be beneficial in improving the outcome of severe traumatic brain injury (TBI) nor has any prophylactically-induced moderate hypothermia shown any beneficial effect on outcome in severe TBI, despite the optimism generated by preclinical studies. This contrasts with the paradox that hypothermia still is the most powerful neuroprotective method in experimental models because of its ability to influence the multiple biochemical cascades that are set in motion after TBI. The aim of this short review is to highlight the most recent developments concerning the pathophysiology of severe TBI, to review new data on thermoregulation and induced hypothermia, the regulation of core and brain temperature in mammals and the multiplicity of effects of hypothermia in the pathophysiology of TBI. Many experimental studies in the last decade have again confirmed that moderate hypothermia confers protection against ischemic and non-ischemic brain hypoxia, traumatic brain injury, anoxic injury following resuscitation after cardiac arrest and other neurological insults. Many posttraumatic adverse events that occur in the injured brain at a cellular and molecular level are highly temperature-sensitive and are thus a good target for induced hypothermia. The basic mechanisms through which hypothermia protects the brain are clearly multifactorial and include at least the following: reduction in brain metabolic rate, effects on cerebral blood flow, reduction of the critical threshold for oxygen delivery, blockade of excitotoxic mechanisms, calcium antagonism, preservation of protein synthesis, reduction of brain thermopooling, a decrease in edema formation, modulation of the inflammatory response, neuroprotection of the white matter and modulation of apoptotic cell death. The new developments discussed in this review indicate that, by targeting many of the abnormal neurochemical cascades initiated after TBI, induced hypothermia may modulate neurotoxicity and, consequently, may play a unique role in opening up new therapeutic avenues for treating severe TBI and improving its devastating effects. Furthermore, greater understanding of the pathophysiology of TBI, new data from both basic and clinical research, the good clinical results obtained in randomized clinical trials in cardiac arrest and better and more reliable cooling methods have given hypothermia a second chance in treating TBI patients. A critical evaluation of hypothermia is therefore mandatory to elucidate the reasons for previous failures and to design further multicenter randomized clinical trials that would definitively confirm or refute the potential of this therapeutic modality in the management of severe traumatic brain injuries.

Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study

PubMed Central

Salem, Heba F; Ahmed, Sayed M; Hassaballah, Ashraf E; Omar, Mahmoud M

2015-01-01

Background The blood–brain barrier prevents many drug moieties from reaching the central nervous system. Therefore, glutathione-modulated nanoliposomes have been engineered to enhance the targeting of flucytosine to the brain. Methods Glutathione-modulated nanoliposomes were prepared by thin-film hydration technique and evaluated in the primary brain cells of rats. Lecithin, cholesterol, and span 65 were mixed at 1:1:1 molar ratio. The molar percentage of PEGylated glutathione varied from 0 mol% to 0.75 mol%. The cellular binding and the uptake of the targeted liposomes were both monitored by epifluorescent microscope and flow cytometry techniques. A biodistribution and a pharmacokinetic study of flucytosine and flucytosine-loaded glutathione–modulated liposomes was carried out to evaluate the in vivo brain-targeting efficiency. Results The size of glutathione-modulated nanoliposomes was <100 nm and the zeta potential was more than −65 mV. The cumulative release reached 70% for certain formulations. The cellular uptake increased as molar percent of glutathione increased to reach the maximum at 0.75 mol%. The uptake of the targeted liposomes by brain cells of the rats was three times greater than that of the nontargeted liposomes. An in vivo study showed that the relative efficiency was 2.632±0.089 and the concentration efficiency was 1.590±0.049, and also, the drug-targeting index was 3.670±0.824. Conclusion Overall, these results revealed that glutathione-PEGylated nanoliposomes enhance the effective delivery of flucytosine to brain and could become a promising new therapeutic option for the treatment of the brain infections. PMID:26229435

Stimuli and consequences of dendritic release of oxytocin within the brain.

PubMed

Neumann, I D

2007-11-01

The brain oxytocin system has served as a distinguished model system in neuroendocrinology to study detailed mechanisms of intracerebral release, in particular of somatodendritic release, and its behavioural and neuroendocrine consequences. It has been shown that oxytocin is released within various brain regions, but evidence for dendritic release is limited to the main sites of oxytocin synthesis, i.e. the hypothalamic SON (supraoptic nucleus) and PVN (paraventricular nucleus). In the present paper, stimuli of dendritic release of oxytocin and the related neuropeptide vasopressin are discussed, including parturition and suckling, i.e. the period of a highly activated brain oxytocin system. Also, exposure to various pharmacological, psychological or physical stressors triggers dendritic oxytocin release, as monitored by intracerebral microdialysis within the SON and PVN during ongoing behavioural testing. So far, dendritic release of the neuropeptide has only been demonstrated within the hypothalamus, but intracerebral oxytocin release has also been found within the central amygdala and the septum in response to various stimuli including stressor exposure. Such a locally released oxytocin modulates physiological and behavioural reproductive functions, emotionality and hormonal stress responses, as it exerts, for example, pro-social, anxiolytic and antistress actions within restricted brain regions. These discoveries make oxytocin a promising neuromodulator of the brain for psychotherapeutic intervention and treatment of numerous psychiatric illnesses, for example, anxiety-related diseases, social phobia, autism and postpartum depression.

Attention Modulates TMS-Locked Alpha Oscillations in the Visual Cortex.

PubMed

Herring, Jim D; Thut, Gregor; Jensen, Ole; Bergmann, Til O

2015-10-28

Cortical oscillations, such as 8-12 Hz alpha-band activity, are thought to subserve gating of information processing in the human brain. While most of the supporting evidence is correlational, causal evidence comes from attempts to externally drive ("entrain") these oscillations by transcranial magnetic stimulation (TMS). Indeed, the frequency profile of TMS-evoked potentials (TEPs) closely resembles that of oscillations spontaneously emerging in the same brain region. However, it is unclear whether TMS-locked and spontaneous oscillations are produced by the same neuronal mechanisms. If so, they should react in a similar manner to top-down modulation by endogenous attention. To test this prediction, we assessed the alpha-like EEG response to TMS of the visual cortex during periods of high and low visual attention while participants attended to either the visual or auditory modality in a cross-modal attention task. We observed a TMS-locked local oscillatory alpha response lasting several cycles after TMS (but not after sham stimulation). Importantly, TMS-locked alpha power was suppressed during deployment of visual relative to auditory attention, mirroring spontaneous alpha amplitudes. In addition, the early N40 TEP component, located at the stimulation site, was amplified by visual attention. The extent of attentional modulation for both TMS-locked alpha power and N40 amplitude did depend, with opposite sign, on the individual ability to modulate spontaneous alpha power at the stimulation site. We therefore argue that TMS-locked and spontaneous oscillations are of common neurophysiological origin, whereas the N40 TEP component may serve as an index of current cortical excitability at the time of stimulation. Copyright © 2015 Herring et al.

Gray Matter Volume in Adolescent Anxiety: An Impact of the Brain-Derived Neurotrophic Factor Val[superscript 66]Met Polymorphism?

ERIC Educational Resources Information Center

Mueller, Sven C.; Aouidad, Aveline; Gorodetsky, Elena; Goldman, David; Pine, Daniel S.; Ernst, Monique

2013-01-01

Objective: Minimal research links anxiety disorders in adolescents to regional gray matter volume (GMV) abnormalities and their modulation by genetic factors. Prior research suggests that a brain-derived neurotrophic factor (BNDF) Val[superscript 66]Met polymorphism may modulate such brain morphometry profiles. Method: Using voxel-based…

Emerging Applications of Therapeutic Ultrasound in Neuro-Oncology: Moving Beyond Tumor Ablation

PubMed Central

Hersh, David S.; Kim, Anthony J.; Winkles, Jeffrey A.; Eisenberg, Howard M.; Woodworth, Graeme F.; Frenkel, Victor

2016-01-01

Transcranial focused ultrasound (FUS) can noninvasively transmit acoustic energy with a high degree of accuracy and safety to targets and regions within the brain. Technological advances, including phased array transducers and real-time temperature monitoring with magnetic resonance (MR) thermometry, have created new opportunities for FUS research and clinical translation. Neuro-oncology, in particular, has become a major area of interest, as FUS offers a multifaceted approach to the treatment of brain tumors. FUS has the potential to (1) generate cytotoxicity within tumor tissue, both directly via thermal ablation and indirectly through radiosensitization and sonodynamic therapy; (2) enhance the delivery of therapeutic agents to brain tumors by transiently opening the blood-brain barrier and/or improving distribution through the brain extracellular space; and (3) modulate the tumor microenvironment in order to generate an immune response. In this review, we describe each of these applications for FUS, the proposed mechanisms of action, and the preclinical and clinical studies that have set the foundation for utilizing FUS in neuro-oncology. PMID:27552589

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.

BAD Modulates Counterregulatory Responses to Hypoglycemia and Protective Glucoprivic Feeding

PubMed Central

Osundiji, Mayowa A.; Godes, Marina L.; Evans, Mark L.; Danial, Nika N.

2011-01-01

Hypoglycemia or glucoprivation triggers protective hormonal counterregulatory and feeding responses to aid the restoration of normoglycemia. Increasing evidence suggests pertinent roles for the brain in sensing glucoprivation and mediating counterregulation, however, the precise nature of the metabolic signals and molecular mediators linking central glucose sensing to effector functions are not fully understood. Here, we demonstrate that protective hormonal and feeding responses to hypoglycemia are regulated by BAD, a BCL-2 family protein with dual functions in apoptosis and metabolism. BAD-deficient mice display impaired glycemic and hormonal counterregulatory responses to systemic glucoprivation induced by 2-deoxy-D-glucose. BAD is also required for proper counterregulatory responses to insulin-induced hypoglycemia as evident from significantly higher glucose infusion rates and lower plasma epinephrine levels during hyperinsulinemic hypoglycemic clamps. Importantly, RNA interference-mediated acute knockdown of Bad in the brain provided independent genetic evidence for its relevance in central glucose sensing and proper neurohumoral responses to glucoprivation. Moreover, BAD deficiency is associated with impaired glucoprivic feeding, suggesting that its role in adaptive responses to hypoglycemia extends beyond hormonal responses to regulation of feeding behavior. Together, these data indicate a previously unappreciated role for BAD in the control of central glucose sensing. PMID:22162752

Consciousness and arousal effects on emotional face processing as revealed by brain oscillations. A gamma band analysis.

PubMed

Balconi, Michela; Lucchiari, Claudio

2008-01-01

It remains an open question whether it is possible to assign a single brain operation or psychological function for facial emotion decoding to a certain type of oscillatory activity. Gamma band activity (GBA) offers an adequate tool for studying cortical activation patterns during emotional face information processing. In the present study brain oscillations were analyzed in response to facial expression of emotions. Specifically, GBA modulation was measured when twenty subjects looked at emotional (angry, fearful, happy, and sad faces) or neutral faces in two different conditions: supraliminal (10 ms) vs subliminal (150 ms) stimulation (100 target-mask pairs for each condition). The results showed that both consciousness and significance of the stimulus in terms of arousal can modulate the power synchronization (ERD decrease) during 150-350 time range: an early oscillatory event showed its peak at about 200 ms post-stimulus. GBA was enhanced by supraliminal more than subliminal elaboration, as well as more by high arousal (anger and fear) than low arousal (happiness and sadness) emotions. Finally a left-posterior dominance for conscious elaboration was found, whereas right hemisphere was discriminant in emotional processing of face in comparison with neutral face.

Real and hypothetical monetary rewards modulate risk taking in the brain.

PubMed

Xu, Sihua; Pan, Yu; Wang, You; Spaeth, Andrea M; Qu, Zhe; Rao, Hengyi

2016-07-07

Both real and hypothetical monetary rewards are widely used as reinforcers in risk taking and decision making studies. However, whether real and hypothetical monetary rewards modulate risk taking and decision making in the same manner remains controversial. In this study, we used event-related potentials (ERP) with a balloon analogue risk task (BART) paradigm to examine the effects of real and hypothetical monetary rewards on risk taking in the brain. Behavioral data showed reduced risk taking after negative feedback (money loss) during the BART with real rewards compared to those with hypothetical rewards, suggesting increased loss aversion with real monetary rewards. The ERP data demonstrated a larger feedback-related negativity (FRN) in response to money loss during risk taking with real rewards compared to those with hypothetical rewards, which may reflect greater prediction error or regret emotion after real monetary losses. These findings demonstrate differential effects of real versus hypothetical monetary rewards on risk taking behavior and brain activity, suggesting a caution when drawing conclusions about real choices from hypothetical studies of intended behavior, especially when large rewards are used. The results have implications for future utility of real and hypothetical monetary rewards in studies of risk taking and decision making.

Music and natural sounds in an auditory steady-state response based brain-computer interface to increase user acceptance.

PubMed

Heo, Jeong; Baek, Hyun Jae; Hong, Seunghyeok; Chang, Min Hye; Lee, Jeong Su; Park, Kwang Suk

2017-05-01

Patients with total locked-in syndrome are conscious; however, they cannot express themselves because most of their voluntary muscles are paralyzed, and many of these patients have lost their eyesight. To improve the quality of life of these patients, there is an increasing need for communication-supporting technologies that leverage the remaining senses of the patient along with physiological signals. The auditory steady-state response (ASSR) is an electro-physiologic response to auditory stimulation that is amplitude-modulated by a specific frequency. By leveraging the phenomenon whereby ASSR is modulated by mind concentration, a brain-computer interface paradigm was proposed to classify the selective attention of the patient. In this paper, we propose an auditory stimulation method to minimize auditory stress by replacing the monotone carrier with familiar music and natural sounds for an ergonomic system. Piano and violin instrumentals were employed in the music sessions; the sounds of water streaming and cicadas singing were used in the natural sound sessions. Six healthy subjects participated in the experiment. Electroencephalograms were recorded using four electrodes (Cz, Oz, T7 and T8). Seven sessions were performed using different stimuli. The spectral power at 38 and 42Hz and their ratio for each electrode were extracted as features. Linear discriminant analysis was utilized to classify the selections for each subject. In offline analysis, the average classification accuracies with a modulation index of 1.0 were 89.67% and 87.67% using music and natural sounds, respectively. In online experiments, the average classification accuracies were 88.3% and 80.0% using music and natural sounds, respectively. Using the proposed method, we obtained significantly higher user-acceptance scores, while maintaining a high average classification accuracy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Haptic contents of a movie dynamically engage the spectator's sensorimotor cortex

PubMed Central

Smeds, Eero; Tikka, Pia; Pihko, Elina; Hari, Riitta; Koskinen, Miika

2016-01-01

Abstract Observation of another person's actions and feelings activates brain areas that support similar functions in the observer, thereby facilitating inferences about the other's mental and bodily states. In real life, events eliciting this kind of vicarious brain activations are intermingled with other complex, ever‐changing stimuli in the environment. One practical approach to study the neural underpinnings of real‐life vicarious perception is to image brain activity during movie viewing. Here the goal was to find out how observed haptic events in a silent movie would affect the spectator's sensorimotor cortex. The functional state of the sensorimotor cortex was monitored by analyzing, in 16 healthy subjects, magnetoencephalographic (MEG) responses to tactile finger stimuli that were presented once per second throughout the session. Using canonical correlation analysis and spatial filtering, consistent single‐trial responses across subjects were uncovered, and their waveform changes throughout the movie were quantified. The long‐latency (85–175 ms) parts of the responses were modulated in concordance with the participants’ average moment‐by‐moment ratings of own engagement in the haptic content of the movie (correlation r = 0.49; ratings collected after the MEG session). The results, obtained by using novel signal‐analysis approaches, demonstrate that the functional state of the human sensorimotor cortex fluctuates in a fine‐grained manner even during passive observation of temporally varying haptic events. Hum Brain Mapp 37:4061–4068, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27364184

The psyche and gastric functions.

PubMed

Nardone, Gerardo; Compare, Debora

2014-01-01

Although the idea that gastric problems are in some way related to mental activity dates back to the beginning of the last century, until now it has received scant attention by physiologists, general practitioners and gastroenterologists. The major breakthrough in understanding the interactions between the central nervous system and the gut was the discovery of the enteric nervous system (ENS) in the 19th century. ENS (also called 'little brain') plays a crucial role in the regulation of the physiological gut functions. Furthermore, the identification of corticotropin-releasing factor (CRF) and the development of specific CRF receptor antagonists have permitted to characterize the neurochemical basis of the stress response. The neurobiological response to stress in mammals involves three key mechanisms: (1) stress is perceived and processed by higher brain centers; (2) the brain mounts a neuroendocrine response by way of the hypothalamic-pituitary-adrenal axis (HPA) and the autonomic nervous system (ANS), and (3) the brain triggers feedback mechanisms by HPA and ANS stimulation to restore homeostasis. Various stressors such as anger, fear, painful stimuli, as well as life or social learning experiences affect both the individual's physiologic and gastric function, revealing a two-way interaction between brain and stomach. There is overwhelming experimental and clinical evidence that stress influences gastric function, thereby outlining the pathogenesis of gastric diseases such as functional dyspepsia, gastroesophageal reflux disease and peptic ulcer disease. A better understanding of the role of pathological stressors in the modulation of disease activity may have important pathogenetic and therapeutic implications. © 2014 S. Karger AG, Basel.

Heat stress, gastrointestinal permeability and interleukin-6 signaling — Implications for exercise performance and fatigue

PubMed Central

Vargas, Nicole; Marino, Frank

2016-01-01

ABSTRACT Exercise in heat stress exacerbates performance decrements compared to normothermic environments. It has been documented that the performance decrements are associated with reduced efferent drive from the central nervous system (CNS), however, specific factors that contribute to the decrements are not completely understood. During exertional heat stress, blood flow is preferentially distributed away from the intestinal area to supply the muscles and brain with oxygen. Consequently, the gastrointestinal barrier becomes increasingly permeable, resulting in the release of lipopolysaccharides (LPS, endotoxin) into the circulation. LPS leakage stimulates an acute-phase inflammatory response, including the release of interleukin (IL)-6 in response to an increasingly endotoxic environment. If LPS translocation is too great, heat shock, neurological dysfunction, or death may ensue. IL-6 acts initially in a pro-inflammatory manner during endotoxemia, but can attenuate the response through signaling the hypothalamic pituitary adrenal (HPA)-axis. Likewise, IL-6 is believed to be a thermoregulatory sensor in the gut during the febrile response, hence highlighting its role in periphery – to – brain communication. Recently, IL-6 has been implicated in signaling the CNS and influencing perceptions of fatigue and performance during exercise. Therefore, due to the cascade of events that occur during exertional heat stress, it is possible that the release of LPS and exacerbated response of IL-6 contributes to CNS modulation during exertional heat stress. The purpose of this review is to evaluate previous literature and discuss the potential role for IL-6 during exertional heat stress to modulate performance in favor of whole body preservation. PMID:27857954

Relationship between Personality Traits and Brain Reward Responses when Playing on a Team

PubMed Central

Morawetz, Carmen; Kirilina, Evgeniya; Baudewig, Juergen; Heekeren, Hauke R.

2014-01-01

Cooperation is an integral part of human social life and we often build teams to achieve certain goals. However, very little is currently understood about emotions with regard to cooperation. Here, we investigated the impact of social context (playing alone versus playing on a team) on emotions while winning or losing a game. We hypothesized that activity in the reward network is modulated by the social context and that personality characteristics might impact team play. We conducted an event-related functional magnetic resonance imaging experiment that involved a simple game of dice. In the team condition, the participant played with a partner against another two-person team. In the single-player condition, the participant played alone against another player. Our results revealed that reward processing in the right amygdala was modulated by the social context. The main effect of outcome (gains versus losses) was associated with increased responses in the reward network. We also found that differences in the reward-related neural response due to social context were associated with specific personality traits. When playing on a team, increased activity in the amygdala during winning was a unique function of openness, while decreased activity in the ventromedial prefrontal cortex and ventral striatum during losing was associated with extraversion and conscientiousness, respectively. In conclusion, we provide evidence that working on a team influences the affective value of a negative outcome by attenuating the negative response associated with it in the amygdala. Our results also show that brain reward responses in a social context are affected by personality traits related to teamwork. PMID:24475262

Relationship between personality traits and brain reward responses when playing on a team.

PubMed

Morawetz, Carmen; Kirilina, Evgeniya; Baudewig, Juergen; Heekeren, Hauke R

2014-01-01

Cooperation is an integral part of human social life and we often build teams to achieve certain goals. However, very little is currently understood about emotions with regard to cooperation. Here, we investigated the impact of social context (playing alone versus playing on a team) on emotions while winning or losing a game. We hypothesized that activity in the reward network is modulated by the social context and that personality characteristics might impact team play. We conducted an event-related functional magnetic resonance imaging experiment that involved a simple game of dice. In the team condition, the participant played with a partner against another two-person team. In the single-player condition, the participant played alone against another player. Our results revealed that reward processing in the right amygdala was modulated by the social context. The main effect of outcome (gains versus losses) was associated with increased responses in the reward network. We also found that differences in the reward-related neural response due to social context were associated with specific personality traits. When playing on a team, increased activity in the amygdala during winning was a unique function of openness, while decreased activity in the ventromedial prefrontal cortex and ventral striatum during losing was associated with extraversion and conscientiousness, respectively. In conclusion, we provide evidence that working on a team influences the affective value of a negative outcome by attenuating the negative response associated with it in the amygdala. Our results also show that brain reward responses in a social context are affected by personality traits related to teamwork.

Heat stress, gastrointestinal permeability and interleukin-6 signaling - Implications for exercise performance and fatigue.

PubMed

Vargas, Nicole; Marino, Frank

2016-01-01

Exercise in heat stress exacerbates performance decrements compared to normothermic environments. It has been documented that the performance decrements are associated with reduced efferent drive from the central nervous system (CNS), however, specific factors that contribute to the decrements are not completely understood. During exertional heat stress, blood flow is preferentially distributed away from the intestinal area to supply the muscles and brain with oxygen. Consequently, the gastrointestinal barrier becomes increasingly permeable, resulting in the release of lipopolysaccharides (LPS, endotoxin) into the circulation. LPS leakage stimulates an acute-phase inflammatory response, including the release of interleukin (IL)-6 in response to an increasingly endotoxic environment. If LPS translocation is too great, heat shock, neurological dysfunction, or death may ensue. IL-6 acts initially in a pro-inflammatory manner during endotoxemia, but can attenuate the response through signaling the hypothalamic pituitary adrenal (HPA)-axis. Likewise, IL-6 is believed to be a thermoregulatory sensor in the gut during the febrile response, hence highlighting its role in periphery - to - brain communication. Recently, IL-6 has been implicated in signaling the CNS and influencing perceptions of fatigue and performance during exercise. Therefore, due to the cascade of events that occur during exertional heat stress, it is possible that the release of LPS and exacerbated response of IL-6 contributes to CNS modulation during exertional heat stress. The purpose of this review is to evaluate previous literature and discuss the potential role for IL-6 during exertional heat stress to modulate performance in favor of whole body preservation.

Brain Hypoactivation, Autonomic Nervous System Dysregulation, and Gonadal Hormones in Depression: A Preliminary Study

PubMed Central

Holsen, Laura M.; Lee, Jong-Hwan; Spaeth, Sarah B.; Ogden, Lauren A.; Klibanski, Anne; Whitfield-Gabrieli, Susan; Sloan, Richard P.; Goldstein, Jill M.

2012-01-01

The comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) is among the 10th leading cause of morbidity and mortality worldwide. Thus, understanding the co-occurrence of these disorders will have major public health significance. MDD is associated with an abnormal stress response, manifested in brain circuitry deficits, gonadal dysfunction, and autonomic nervous system (ANS) dysregulation. Contribution of the relationships between these systems to the pathophysiology of MDD is not well understood. The objective of this preliminary study was to investigate, in parallel, relationships between HPG-axis functioning, stress response circuitry activation, and parasympathetic reactivity in healthy controls and women with MDD. Using fMRI with pulse oximetry [from which we calculated the high frequency (HF) component of R-R interval variability (HF-RRV), a measure of parasympathetic modulation] and hormone data, we studied eight women with recurrent MDD in remission and six controls during a stress response paradigm. We demonstrated that hypoactivations of hypothalamus, amygdala, hippocampus, anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and subgenual ACC were associated with lower parasympathetic cardiac modulation in MDD women. Estradiol and progesterone attenuated group differences in the effect of HF-RRV on hypoactivation in the amygdala, hippocampus, ACC, and OFC in MDD women. Findings have implications for understanding the relationship between mood, arousal, heart regulation, and gonadal hormones, and may provide insights into MDD and CVD risk comorbidity. PMID:22395084

Resveratrol Confers Protection against Rotenone-Induced Neurotoxicity by Modulating Myeloperoxidase Levels in Glial Cells

PubMed Central

Chang, Chi Young; Choi, Dong-Kug; Lee, Dae Kee; Hong, Young Jun; Park, Eun Jung

2013-01-01

Myeloperoxidase (MPO) functions as a key molecular component of the host defense system against diverse pathogens. We have previously reported that increased MPO levels and activity is a distinguishing feature of rotenone-exposed glial cells, and that either overactivation or deficiency of MPO leads to pathological conditions in the brain. Here, we provide that modulation of MPO levels in glia by resveratrol confers protective effects on rotenone-induced neurotoxicity. We show that resveratrol significantly reduced MPO levels but did not trigger abnormal nitric oxide (NO) production in microglia and astrocytes. Resveratrol-induced down-regulation of MPO, in the absence of an associated overproduction of NO, markedly attenuated rotenone-triggered inflammatory responses including phagocytic activity and reactive oxygen species production in primary microglia and astrocytes. In addition, impaired responses of primary mixed glia from Mpo −/− mice to rotenone were relieved by treatment with resveratrol. We further show that rotenone-induced neuronal injury, particularly dopaminergic cell death, was attenuated by resveratrol in neuron-glia co-cultures, but not in neurons cultured alone. Similar regulatory effects of resveratrol on MPO levels were observed in microglia treated with MPP+, another Parkinson’s disease-linked neurotoxin, supporting the beneficial effects of resveratrol on the brain. Collectively, our findings provide that resveratrol influences glial responses to rotenone by regulating both MPO and NO, and thus protects against rotenone-induced neuronal injury. PMID:23593274

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.

Brain-derived neurotrophic factor in the nucleus tractus solitarii modulates glucose homeostasis after carotid chemoreceptor stimulation in rats.

PubMed

Montero, Sergio; Cuéllar, Ricardo; Lemus, Mónica; Avalos, Reyes; Ramírez, Gladys; de Álvarez-Buylla, Elena Roces

2012-01-01

Neuronal systems, which regulate energy intake, energy expenditure and endogenous glucose production, sense and respond to input from hormonal related signals that convey information from body energy availability. Carotid chemoreceptors (CChr) function as sensors for circulating glucose levels and contribute to glycemic counterregulatory responses. Brain-derived neurotrophic factor (BDNF) that plays an important role in the endocrine system to regulate glucose metabolism could play a role in hyperglycemic glucose reflex with brain glucose retention (BGR) evoked by anoxic CChr stimulation. Infusing BDNF into the nucleus tractus solitarii (NTS) before CChr stimulation, showed that this neurotrophin increased arterial glucose and BGR. In contrast, BDNF receptor (TrkB) antagonist (K252a) infusions in NTS resulted in a decrease in both glucose variables.

Teaching About "Brain and Learning" in High School Biology Classes: Effects on Teachers' Knowledge and Students' Theory of Intelligence.

PubMed

Dekker, Sanne; Jolles, Jelle

2015-01-01

This study evaluated a new teaching module about "Brain and Learning" using a controlled design. The module was implemented in high school biology classes and comprised three lessons: (1) brain processes underlying learning; (2) neuropsychological development during adolescence; and (3) lifestyle factors that influence learning performance. Participants were 32 biology teachers who were interested in "Brain and Learning" and 1241 students in grades 8-9. Teachers' knowledge and students' beliefs about learning potential were examined using online questionnaires. Results indicated that before intervention, biology teachers were significantly less familiar with how the brain functions and develops than with its structure and with basic neuroscientific concepts (46 vs. 75% correct answers). After intervention, teachers' knowledge of "Brain and Learning" had significantly increased (64%), and more students believed that intelligence is malleable (incremental theory). This emphasizes the potential value of a short teaching module, both for improving biology teachers' insights into "Brain and Learning," and for changing students' beliefs about intelligence.

Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness.

PubMed

Diwadkar, Vaibhav A; Bellani, Marcella; Chowdury, Asadur; Savazzi, Silvia; Perlini, Cinzia; Marinelli, Veronica; Zoccatelli, Giada; Alessandrini, Franco; Ciceri, Elisa; Rambaldelli, Gianluca; Ruggieri, Mirella; Carlo Altamura, A; Marzi, Carlo A; Brambilla, Paolo

2017-08-14

Because the visual cortices are contra-laterally organized, inter-hemispheric transfer tasks have been used to behaviorally probe how information briefly presented to one hemisphere of the visual cortex is integrated with responses resulting from the ipsi- or contra-lateral motor cortex. By forcing rapid information exchange across diverse regions, these tasks robustly activate not only gray matter regions, but also white matter tracts. It is likely that the response hand itself (dominant or non-dominant) modulates gray and white matter activations during within and inter-hemispheric transfer. Yet the role of uni-manual responses and/or right hand dominance in modulating brain activations during such basic tasks is unclear. Here we investigated how uni-manual responses with either hand modulated activations during a basic visuo-motor task (the established Poffenberger paradigm) alternating between inter- and within-hemispheric transfer conditions. In a large sample of strongly right-handed adults (n = 49), we used a factorial combination of transfer condition [Inter vs. Within] and response hand [Dominant(Right) vs. Non-Dominant (Left)] to discover fMRI-based activations in gray matter, and in narrowly defined white matter tracts. These tracts were identified using a priori probabilistic white matter atlases. Uni-manual responses with the right hand strongly modulated activations in gray matter, and notably in white matter. Furthermore, when responding with the left hand, activations during inter-hemispheric transfer were strongly predicted by the degree of right-hand dominance, with increased right-handedness predicting decreased fMRI activation. Finally, increasing age within the middle-aged sample was associated with a decrease in activations. These results provide novel evidence of complex relationships between uni-manual responses in right-handed subjects, and activations during within- and inter-hemispheric transfer suggest that the organization of the motor system exerts sophisticated functional effects. Moreover, our evidence of activation in white matter tracts is consistent with prior studies, confirming fMRI-detectable white matter activations which are systematically modulated by experimental condition.

Responsibility modulates pain-matrix activation elicited by the expressions of others in pain

PubMed Central

Cui, Fang; Abdelgabar, Abdel-Rahman; Keysers, Christian; Gazzola, Valeria

2015-01-01

Here we examine whether brain responses to dynamic facial expressions of pain are influenced by our responsibility for the observed pain. Participants played a flanker task with a confederate. Whenever either erred, the confederate was seen to receive a noxious shock. Using functional magnetic resonance imaging, we found that regions of the functionally localized pain-matrix of the participants (the anterior insula in particular) were activated most strongly when seeing the confederate receive a noxious shock when only the participant had erred (and hence had full responsibility). When both or only the confederate had erred (i.e. participant's shared or no responsibility), significantly weaker vicarious pain-matrix activations were measured. PMID:25800210

Three-dimensional culture conditions differentially affect astrocyte modulation of brain endothelial barrier function in response to transforming growth factor β1.

PubMed

Hawkins, Brian T; Grego, Sonia; Sellgren, Katelyn L

2015-05-22

Blood-brain barrier (BBB) function is regulated by dynamic interactions among cell types within the neurovascular unit, including astrocytes and endothelial cells. Co-culture models of the BBB typically involve astrocytes seeded on two-dimensional (2D) surfaces, which recent studies indicate cause astrocytes to express a phenotype similar to that of reactive astrocytes in situ. We hypothesized that the culture conditions of astrocytes would differentially affect their ability to modulate BBB function in vitro. Brain endothelial cells were grown alone or in co-culture with astrocytes. Astrocytes were grown either as conventional (2D) monolayers, or in a collagen-based gel which allows them to grow in a three-dimensional (3D) construct. Astrocytes were viable in 3D conditions, and displayed a marked reduction in their expression of glial fibrillary acidic protein (GFAP), suggesting reduced activation. Stimulation of astrocytes with transforming growth factor (TGF)β1 decreased transendothelial electrical resistance (TEER) and reduced expression of claudin-5 in co-cultures, whereas treatment of endothelial cells in the absence of astrocytes was without effect. The effect of TGFβ1 on TEER was significantly more pronounced in endothelial cells cultured with 3D astrocytes compared to 2D astrocytes. These results demonstrate that astrocyte culture conditions differentially affect their ability to modulate brain endothelial barrier function, and suggest a direct relationship between reactive gliosis and BBB permeability. Moreover, these studies demonstrate the potential importance of physiologically relevant culture conditions to in vitro modeling of disease processes that affect the neurovascular unit. Copyright © 2015 Elsevier B.V. All rights reserved.

User Experience May be Producing Greater Heart Rate Variability than Motor Imagery Related Control Tasks during the User-System Adaptation in Brain-Computer Interfaces

PubMed Central

Alonso-Valerdi, Luz M.; Gutiérrez-Begovich, David A.; Argüello-García, Janet; Sepulveda, Francisco; Ramírez-Mendoza, Ricardo A.

2016-01-01

Brain-computer interface (BCI) is technology that is developing fast, but it remains inaccurate, unreliable and slow due to the difficulty to obtain precise information from the brain. Consequently, the involvement of other biosignals to decode the user control tasks has risen in importance. A traditional way to operate a BCI system is via motor imagery (MI) tasks. As imaginary movements activate similar cortical structures and vegetative mechanisms as a voluntary movement does, heart rate variability (HRV) has been proposed as a parameter to improve the detection of MI related control tasks. However, HR is very susceptible to body needs and environmental demands, and as BCI systems require high levels of attention, perceptual processing and mental workload, it is important to assess the practical effectiveness of HRV. The present study aimed to determine if brain and heart electrical signals (HRV) are modulated by MI activity used to control a BCI system, or if HRV is modulated by the user perceptions and responses that result from the operation of a BCI system (i.e., user experience). For this purpose, a database of 11 participants who were exposed to eight different situations was used. The sensory-cognitive load (intake and rejection tasks) was controlled in those situations. Two electrophysiological signals were utilized: electroencephalography and electrocardiography. From those biosignals, event-related (de-)synchronization maps and event-related HR changes were respectively estimated. The maps and the HR changes were cross-correlated in order to verify if both biosignals were modulated due to MI activity. The results suggest that HR varies according to the experience undergone by the user in a BCI working environment, and not because of the MI activity used to operate the system. PMID:27458384

Decreases in Short Term Memory, IQ, and Altered Brain Metabolic Ratios in Urban Apolipoprotein ε4 Children Exposed to Air Pollution.

PubMed

Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Franco-Lira, Maricela; Zhu, Hongtu; Lu, Zhaohua; Solorio, Edelmira; Torres-Jardón, Ricardo; D'Angiulli, Amedeo

2015-01-01

Children's urban air pollution exposures result in systemic and brain inflammation and the early hallmarks of Alzheimer's disease (AD). The apolipoprotein E (APOE) ε4 allele is the most prevalent genetic risk for AD. We assessed whether APOE in healthy children modulates cognition, olfaction, and metabolic brain indices. The Wechsler Intelligence Scale for Children (WISC-R) and the University of Pennsylvania Smell Identification Test were administered to 50 Mexico City Metropolitan Area children (13.4 ± 4.8 years, 28 APOE ε3 and 22 APOE ε4). N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, myo-inositol (mI)/Cr, and NAA/mI were calculated using proton magnetic resonance spectroscopy in the white matter of the frontal and parietal lobes, hippocampus, and pons. APOE ε4 versus ε3 children had a reduced NAA/Cr ratio in the right frontal white matter and decrements on attention, short-term memory, and below-average scores in Verbal and Full Scale IQ (>10 points). APOE modulated the group effects between WISC-R and left frontal and parietal white matter, and hippocampus metabolites. Soap was the predominantly failed odor in urban children and, in APOE ε4 versus ε3 carriers, strongly correlated with left hippocampus mI/Cr ratio. APOE modulates responses to air pollution in the developing brain. APOE ε4 carriers could have a higher risk of developing early AD if they reside in a polluted environment. APOE, cognition, and olfaction testing and targeted magnetic resonance spectroscopy may contribute to the assessment of urban children and their results could provide new paths toward the unprecedented opportunity for early neuroprotection and AD prevention.

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

PubMed

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

2015-01-01

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

The microbiome-gut-brain axis: from bowel to behavior.

PubMed

Cryan, J F; O'Mahony, S M

2011-03-01

The ability of gut microbiota to communicate with the brain and thus modulate behavior is emerging as an exciting concept in health and disease. The enteric microbiota interacts with the host to form essential relationships that govern homeostasis. Despite the unique enteric bacterial fingerprint of each individual, there appears to be a certain balance that confers health benefits. It is, therefore, reasonable to note that a decrease in the desirable gastrointestinal bacteria will lead to deterioration in gastrointestinal, neuroendocrine or immune relationships and ultimately disease. Therefore, studies focusing on the impact of enteric microbiota on the host and in particular on the central nervous system are essential to our understanding of the influence of this system. Recent studies published in this Journal demonstrate that germ-free mice display alterations in stress-responsivity, central neurochemistry and behavior indicative of a reduction in anxiety in comparison to conventional mice. Such data offer the enticing proposition that specific modulation of the enteric microbiota may be a useful strategy for stress-related disorders and for modulating the co-morbid aspects of gastrointestinal disorders such as irritable bowel syndrome and inflammatory bowel disease. © 2011 Blackwell Publishing Ltd.

Aberrant Modulation of Brain Oscillatory Activity and Attentional Impairment in Attention-Deficit/Hyperactivity Disorder.

PubMed

Lenartowicz, Agatha; Mazaheri, Ali; Jensen, Ole; Loo, Sandra K

2018-01-01

Electroencephalography and magnetoencephalography are noninvasive neuroimaging techniques that have been used extensively to study various resting-state and cognitive processes in the brain. The purpose of this review is to highlight a number of recent studies that have investigated the alpha band (8-12 Hz) oscillatory activity present in magnetoencephalography and electroencephalography, to provide new insights into the maladaptive network activity underlying attentional impairments in attention-deficit/hyperactivity disorder (ADHD). Studies reviewed demonstrate that event-related decrease in alpha is attenuated during visual selective attention, primarily in ADHD inattentive type, and is often significantly associated with accuracy and reaction time during task performance. Furthermore, aberrant modulation of alpha activity has been reported across development and may have abnormal or atypical lateralization patterns in ADHD. Modulations in the alpha band thus represent a robust, relatively unexplored putative biomarker of attentional impairment and a strong prospect for future studies aimed at examining underlying neural mechanisms and treatment response among individuals with ADHD. Potential limitations of its use as a diagnostic biomarker and directions for future research are discussed. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Dissociable influences of opiates and expectations on pain

PubMed Central

Atlas, Lauren Y.; Whittington, Robert A.; Lindquist, Martin A.; Wielgosz, Joe; Sonty, Nomita; Wager, Tor D.

2012-01-01

Placebo treatments and opiate drugs are thought to have common effects on the opioid system and pain-related brain processes. This has created excitement about the potential for expectations to modulate drug effects themselves. If drug effects differ as a function of belief, this would challenge the assumptions underlying the standard clinical trial. We conducted two studies to directly examine the relationship between expectations and opioid analgesia. We administered the opioid agonist remifentanil to human subjects during experimental thermal pain and manipulated participants’ knowledge of drug delivery using an open-hidden design. This allowed us to test drug effects, expectancy (knowledge) effects, and their interactions on pain reports and pain-related responses in the brain. Remifentanil and expectancy both reduced pain, but drug effects on pain reports and fMRI activity did not interact with expectancy. Regions associated with pain processing showed drug-induced modulation during both Open and Hidden conditions, with no differences in drug effects as a function of expectation. Instead, expectancy modulated activity in frontal cortex, with a separable time course from drug effects. These findings reveal that opiates and placebo treatments both influence clinically relevant outcomes and operate without mutual interference. PMID:22674280

Food can lift mood by affecting mood-regulating neurocircuits via a serotonergic mechanism.

PubMed

Kroes, Marijn C W; van Wingen, Guido A; Wittwer, Jonas; Mohajeri, M Hasan; Kloek, Joris; Fernández, Guillén

2014-01-01

It is commonly assumed that food can affect mood. One prevalent notion is that food containing tryptophan increases serotonin levels in the brain and alters neural processing in mood-regulating neurocircuits. However, tryptophan competes with other long-neutral-amino-acids (LNAA) for transport across the blood-brain-barrier, a limitation that can be mitigated by increasing the tryptophan/LNAA ratio. We therefore tested in a double-blind, placebo-controlled crossover study (N=32) whether a drink with a favourable tryptophan/LNAA ratio improves mood and modulates specific brain processes as assessed by functional magnetic resonance imaging (fMRI). We show that one serving of this drink increases the tryptophan/LNAA ratio in blood plasma, lifts mood in healthy young women and alters task-specific and resting-state processing in brain regions implicated in mood regulation. Specifically, Test-drink consumption reduced neural responses of the dorsal caudate nucleus during reward anticipation, increased neural responses in the dorsal cingulate cortex during fear processing, and increased ventromedial prefrontal-lateral prefrontal connectivity under resting-state conditions. Our results suggest that increasing tryptophan/LNAA ratios can lift mood by affecting mood-regulating neurocircuits. © 2013 Elsevier Inc. All rights reserved.

Host matrix metalloproteinases in cerebral malaria: new kids on the block against blood–brain barrier integrity?

PubMed Central

2014-01-01

Cerebral malaria (CM) is a life-threatening complication of falciparum malaria, associated with high mortality rates, as well as neurological impairment in surviving patients. Despite disease severity, the etiology of CM remains elusive. Interestingly, although the Plasmodium parasite is sequestered in cerebral microvessels, it does not enter the brain parenchyma: so how does Plasmodium induce neuronal dysfunction? Several independent research groups have suggested a mechanism in which increased blood–brain barrier (BBB) permeability might allow toxic molecules from the parasite or the host to enter the brain. However, the reported severity of BBB damage in CM is variable depending on the model system, ranging from mild impairment to full BBB breakdown. Moreover, the factors responsible for increased BBB permeability are still unknown. Here we review the prevailing theories on CM pathophysiology and discuss new evidence from animal and human CM models implicating BBB damage. Finally, we will review the newly-described role of matrix metalloproteinases (MMPs) and BBB integrity. MMPs comprise a family of proteolytic enzymes involved in modulating inflammatory response, disrupting tight junctions, and degrading sub-endothelial basal lamina. As such, MMPs represent potential innovative drug targets for CM. PMID:24467887

Learning-induced neural plasticity of speech processing before birth

PubMed Central

Partanen, Eino; Kujala, Teija; Näätänen, Risto; Liitola, Auli; Sambeth, Anke; Huotilainen, Minna

2013-01-01

Learning, the foundation of adaptive and intelligent behavior, is based on plastic changes in neural assemblies, reflected by the modulation of electric brain responses. In infancy, auditory learning implicates the formation and strengthening of neural long-term memory traces, improving discrimination skills, in particular those forming the prerequisites for speech perception and understanding. Although previous behavioral observations show that newborns react differentially to unfamiliar sounds vs. familiar sound material that they were exposed to as fetuses, the neural basis of fetal learning has not thus far been investigated. Here we demonstrate direct neural correlates of human fetal learning of speech-like auditory stimuli. We presented variants of words to fetuses; unlike infants with no exposure to these stimuli, the exposed fetuses showed enhanced brain activity (mismatch responses) in response to pitch changes for the trained variants after birth. Furthermore, a significant correlation existed between the amount of prenatal exposure and brain activity, with greater activity being associated with a higher amount of prenatal speech exposure. Moreover, the learning effect was generalized to other types of similar speech sounds not included in the training material. Consequently, our results indicate neural commitment specifically tuned to the speech features heard before birth and their memory representations. PMID:23980148

AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates aging-related neuroinflammation.

PubMed

Jiang, Teng; Xue, Liu-Jun; Yang, Yang; Wang, Qing-Guang; Xue, Xiao; Ou, Zhou; Gao, Qing; Shi, Jian-Quan; Wu, Liang; Zhang, Ying-Dong

2018-04-17

During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7). More importantly, we provided evidence that AVE0991, a nonpeptide analogue of Ang-(1-7), attenuated the aging-related neuroinflammation via suppression of microglial-mediated inflammatory response through a MAS1 receptor-dependent manner. Meanwhile, this protective effect might be ascribed to the M2 activation of microglia induced by AVE0991. Taken together, these findings reveal the association of Ang-(1-7) with the inflammatory response in the aged brain and uncover the potential of its nonpeptide analogue AVE0991 in attenuation of aging-related neuroinflammation.

Dynamic pupillary exchange engages brain regions encoding social salience

PubMed Central

Harrison, Neil A.; Gray, Marcus A.; Critchley, Hugo D.

2008-01-01

Covert exchange of autonomic responses may shape social affective behavior, as observed in mirroring of pupillary responses during sadness processing. We examined how, independent of facial emotional expression, dynamic coherence between one's own and another's pupil size modulates regional brain activity. Fourteen subjects viewed pairs of eye stimuli while undergoing fMRI. Using continuous pupillometry biofeedback, the size of the observed pupils was varied, correlating positively or negatively with changes in participants’ own pupils. Viewing both static and dynamic stimuli activated right fusiform gyrus. Observing dynamically changing pupils activated STS and amygdala, regions engaged by non-static and salient facial features. Discordance between observed and observer's pupillary changes enhanced activity within bilateral anterior insula, left amygdala and anterior cingulate. In contrast, processing positively correlated pupils enhanced activity within left frontal operculum. Our findings suggest pupillary signals are monitored continuously during social interactions and that incongruent changes activate brain regions involved in tracking motivational salience and attentionally meaningful information. Naturalistically, dynamic coherence in pupillary change follows fluctuations in ambient light. Correspondingly, in social contexts discordant pupil response is likely to reflect divergence of dispositional state. Our data provide empirical evidence for an autonomically mediated extension of forward models of motor control into social interaction. PMID:19048432

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

PubMed

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

2017-10-01

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

Aging effects on DNA methylation modules in human brain and blood tissue

PubMed Central

2012-01-01

Background Several recent studies reported aging effects on DNA methylation levels of individual CpG dinucleotides. But it is not yet known whether aging-related consensus modules, in the form of clusters of correlated CpG markers, can be found that are present in multiple human tissues. Such a module could facilitate the understanding of aging effects on multiple tissues. Results We therefore employed weighted correlation network analysis of 2,442 Illumina DNA methylation arrays from brain and blood tissues, which enabled the identification of an age-related co-methylation module. Module preservation analysis confirmed that this module can also be found in diverse independent data sets. Biological evaluation showed that module membership is associated with Polycomb group target occupancy counts, CpG island status and autosomal chromosome location. Functional enrichment analysis revealed that the aging-related consensus module comprises genes that are involved in nervous system development, neuron differentiation and neurogenesis, and that it contains promoter CpGs of genes known to be down-regulated in early Alzheimer's disease. A comparison with a standard, non-module based meta-analysis revealed that selecting CpGs based on module membership leads to significantly increased gene ontology enrichment, thus demonstrating that studying aging effects via consensus network analysis enhances the biological insights gained. Conclusions Overall, our analysis revealed a robustly defined age-related co-methylation module that is present in multiple human tissues, including blood and brain. We conclude that blood is a promising surrogate for brain tissue when studying the effects of age on DNA methylation profiles. PMID:23034122

Histone Deacetylase Inhibitor Trichostatin A Ameliorated Endotoxin-Induced Neuroinflammation and Cognitive Dysfunction

PubMed Central

Chen, Yeong-Chang; Wei, Tsui-Shan; Sun, Ding-Ping; Wang, Jhi-Joung; Yeh, Ching-Hua

2015-01-01

Excessive production of cytokines by microglia may cause cognitive dysfunction and long-lasting behavioral changes. Activating the peripheral innate immune system stimulates cytokine secretion in the central nervous system, which modulates cognitive function. Histone deacetylases (HDACs) modulate cytokine synthesis and release. Trichostatin A (TSA), an HDAC inhibitor, is documented to be anti-inflammatory and neuroprotective. We investigated whether TSA reduces lipopolysaccharide- (LPS-) induced neuroinflammation and cognitive dysfunction. ICR mice were first intraperitoneally (i.p.) injected with vehicle or TSA (0.3 mg/kg). One hour later, they were injected (i.p.) with saline or Escherichia coli LPS (1 mg/kg). We analyzed the food and water intake, body weight loss, and sucrose preference of the injected mice and then determined the microglia activation and inflammatory cytokine expression in the brains of LPS-treated mice and LPS-treated BV-2 microglial cells. In the TSA-pretreated mice, microglial activation was lower, anhedonia did not occur, and LPS-induced cognitive dysfunction (anorexia, weight loss, and social withdrawal) was attenuated. Moreover, mRNA expression of HDAC2, HDAC5, indoleamine 2,3-dioxygenase (IDO), TNF-α, MCP-1, and IL-1β in the brain of LPS-challenged mice and in the LPS-treated BV-2 microglial cells was lower. TSA diminished LPS-induced inflammatory responses in the mouse brain and modulated the cytokine-associated changes in cognitive function, which might be specifically related to reducing HDAC2 and HDAC5 expression. PMID:26273133

Δ9-Tetrahydrocannabinol (Δ9-THC) Promotes Neuroimmune-Modulatory MicroRNA Profile in Striatum of Simian Immunodeficiency Virus (SIV)-Infected Macaques.

PubMed

Simon, Liz; Song, Keijing; Vande Stouwe, Curtis; Hollenbach, Andrew; Amedee, Angela; Mohan, Mahesh; Winsauer, Peter; Molina, Patricia

2016-03-01

Cannabinoid administration before and after simian immunodeficiency virus (SIV)-inoculation ameliorated disease progression and decreased inflammation in male rhesus macaques. Δ9-tetrahydrocannabinol (Δ9-THC) did not increase viral load in brain tissue or produce additive neuropsychological impairment in SIV-infected macaques. To determine if the neuroimmunomodulation of Δ9-THC involved differential microRNA (miR) expression, miR expression in the striatum of uninfected macaques receiving vehicle (VEH) or Δ9-THC (THC) and SIV-infected macaques administered either vehicle (VEH/SIV) or Δ9-THC (THC/SIV) was profiled using next generation deep sequencing. Among the 24 miRs that were differentially expressed among the four groups, 16 miRs were modulated by THC in the presence of SIV. These 16 miRs were classified into four categories and the biological processes enriched by the target genes determined. Our results indicate that Δ9-THC modulates miRs that regulate mRNAs of proteins involved in 1) neurotrophin signaling, 2) MAPK signaling, and 3) cell cycle and immune response thus promoting an overall neuroprotective environment in the striatum of SIV-infected macaques. This is also reflected by increased Brain Derived Neurotrophic Factor (BDNF) and decreased proinflammatory cytokine expression compared to the VEH/SIV group. Whether Δ9-THC-mediated modulation of epigenetic mechanisms provides neuroprotection in other regions of the brain and during chronic SIV-infection remains to be determined.

Processing of emotional stimuli is reflected by modulations of beta band activity in the subgenual anterior cingulate cortex in patients with treatment resistant depression.

PubMed

Huebl, Julius; Brücke, Christof; Merkl, Angela; Bajbouj, Malek; Schneider, Gerd-Helge; Kühn, Andrea A

2016-08-01

Deep brain stimulation (DBS) of the subgenual anterior cingulate cortex (sgACC) has emerged as a new therapeutic option in patients with treatment resistant depression (TRD). At the same time, DBS offers a unique opportunity as an innovative research tool to study brain function in vivo Indirect measures of brain function such as positron-emission-tomography imaging findings have revealed a hypermetabolism in the sgACC area in patients with TRD that normalizes in parallel with treatment response to DBS. We used direct intracranial recordings via implanted DBS electrodes to study the neuronal oscillatory activity in the sgACC area during a picture viewing task including emotional and neutral stimuli in eight patients with TRD who underwent DBS.We found a stimulus-induced decrease in beta-band and increase in gamma-band activity, with a main effect of valence for event-related desynchronisation in the beta-frequency range (14-30 Hz). Unpleasant stimuli induced the strongest and most sustained beta-power decrease. The degree of beta-band modulation upon emotional stimuli correlated with the patients' rating of stimulus valence. Our findings confirm the involvement of the sgACC area in emotional processing that was more enhanced for unpleasant stimuli. Moreover, stimulus evaluation may be encoded by modulations of beta-band activity. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Neural correlates of erotic stimulation under different levels of female sexual hormones.

PubMed

Abler, Birgit; Kumpfmüller, Daniela; Grön, Georg; Walter, Martin; Stingl, Julia; Seeringer, Angela

2013-01-01

Previous studies have demonstrated variable influences of sexual hormonal states on female brain activation and the necessity to control for these in neuroimaging studies. However, systematic investigations of these influences, particularly those of hormonal contraceptives as compared to the physiological menstrual cycle are scarce. In the present study, we investigated the hormonal modulation of neural correlates of erotic processing in a group of females under hormonal contraceptives (C group; N = 12), and a different group of females (nC group; N = 12) not taking contraceptives during their mid-follicular and mid-luteal phases of the cycle. We used functional magnetic resonance imaging to measure hemodynamic responses as an estimate of brain activation during three different experimental conditions of visual erotic stimulation: dynamic videos, static erotic pictures, and expectation of erotic pictures. Plasma estrogen and progesterone levels were assessed in all subjects. No strong hormonally modulating effect was detected upon more direct and explicit stimulation (viewing of videos or pictures) with significant activations in cortical and subcortical brain regions previously linked to erotic stimulation consistent across hormonal levels and stimulation type. Upon less direct and less explicit stimulation (expectation), activation patterns varied between the different hormonal conditions with various, predominantly frontal brain regions showing significant within- or between-group differences. Activation in the precentral gyrus during the follicular phase in the nC group was found elevated compared to the C group and positively correlated with estrogen levels. From the results we conclude that effects of hormonal influences on brain activation during erotic stimulation are weak if stimulation is direct and explicit but that female sexual hormones may modulate more subtle aspects of sexual arousal and behaviour as involved in sexual expectation. Results may provide a basis for future imaging studies on sexual processing in females, especially in the context of less explicit erotic stimulation.

Neural Correlates of Erotic Stimulation under Different Levels of Female Sexual Hormones

PubMed Central

Abler, Birgit; Kumpfmüller, Daniela; Grön, Georg; Walter, Martin; Stingl, Julia; Seeringer, Angela

2013-01-01

Previous studies have demonstrated variable influences of sexual hormonal states on female brain activation and the necessity to control for these in neuroimaging studies. However, systematic investigations of these influences, particularly those of hormonal contraceptives as compared to the physiological menstrual cycle are scarce. In the present study, we investigated the hormonal modulation of neural correlates of erotic processing in a group of females under hormonal contraceptives (C group; N = 12), and a different group of females (nC group; N = 12) not taking contraceptives during their mid-follicular and mid-luteal phases of the cycle. We used functional magnetic resonance imaging to measure hemodynamic responses as an estimate of brain activation during three different experimental conditions of visual erotic stimulation: dynamic videos, static erotic pictures, and expectation of erotic pictures. Plasma estrogen and progesterone levels were assessed in all subjects. No strong hormonally modulating effect was detected upon more direct and explicit stimulation (viewing of videos or pictures) with significant activations in cortical and subcortical brain regions previously linked to erotic stimulation consistent across hormonal levels and stimulation type. Upon less direct and less explicit stimulation (expectation), activation patterns varied between the different hormonal conditions with various, predominantly frontal brain regions showing significant within- or between-group differences. Activation in the precentral gyrus during the follicular phase in the nC group was found elevated compared to the C group and positively correlated with estrogen levels. From the results we conclude that effects of hormonal influences on brain activation during erotic stimulation are weak if stimulation is direct and explicit but that female sexual hormones may modulate more subtle aspects of sexual arousal and behaviour as involved in sexual expectation. Results may provide a basis for future imaging studies on sexual processing in females, especially in the context of less explicit erotic stimulation. PMID:23418428

Modulation of experimental arthritis by vagal sensory and central brain stimulation.

PubMed

Bassi, Gabriel Shimizu; Dias, Daniel Penteado Martins; Franchin, Marcelo; Talbot, Jhimmy; Reis, Daniel Gustavo; Menezes, Gustavo Batista; Castania, Jaci Airton; Garcia-Cairasco, Norberto; Resstel, Leonardo Barbosa Moraes; Salgado, Helio Cesar; Cunha, Fernando Queiróz; Cunha, Thiago Mattar; Ulloa, Luis; Kanashiro, Alexandre

2017-08-01

Articular inflammation is a major clinical burden in multiple inflammatory diseases, especially in rheumatoid arthritis. Biological anti-rheumatic drug therapies are expensive and increase the risk of systemic immunosuppression, infections, and malignancies. Here, we report that vagus nerve stimulation controls arthritic joint inflammation by inducing local regulation of innate immune response. Most of the previous studies of neuromodulation focused on vagal regulation of inflammation via the efferent peripheral pathway toward the viscera. Here, we report that vagal stimulation modulates arthritic joint inflammation through a novel "afferent" pathway mediated by the locus coeruleus (LC) of the central nervous system. Afferent vagal stimulation activates two sympatho-excitatory brain areas: the paraventricular hypothalamic nucleus (PVN) and the LC. The integrity of the LC, but not that of the PVN, is critical for vagal control of arthritic joint inflammation. Afferent vagal stimulation suppresses articular inflammation in the ipsilateral, but not in the contralateral knee to the hemispheric LC lesion. Central stimulation is followed by subsequent activation of joint sympathetic nerve terminals inducing articular norepinephrine release. Selective adrenergic beta-blockers prevent the effects of articular norepinephrine and thereby abrogate vagal control of arthritic joint inflammation. These results reveals a novel neuro-immune brain map with afferent vagal signals controlling side-specific articular inflammation through specific inflammatory-processing brain centers and joint sympathetic innervations. Copyright © 2017 Elsevier Inc. All rights reserved.

Interferon-β Modulates Inflammatory Response in Cerebral Ischemia.

PubMed

Kuo, Ping-Chang; Scofield, Barbara A; Yu, I-Chen; Chang, Fen-Lei; Ganea, Doina; Yen, Jui-Hung

2016-01-08

Stroke is a leading cause of death in the world. In >80% of strokes, the initial acute phase of ischemic injury is due to the occlusion of a blood vessel resulting in severe focal hypoperfusion, excitotoxicity, and oxidative damage. Interferon-β (IFNβ), a cytokine with immunomodulatory properties, was approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis for more than a decade. Its anti-inflammatory properties and well-characterized safety profile suggest that IFNβ has therapeutic potential for the treatment of ischemic stroke. We investigated the therapeutic effect of IFNβ in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNβ not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNβ modulates ischemic brain inflammation were identified. IFNβ reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD4(+) T cells, and γδ T cells; inhibited the production of inflammatory mediators; suppressed the expression of adhesion molecules on brain endothelial cells; and repressed microglia activation in the ischemic brain. Our results demonstrate that IFNβ exerts a protective effect against ischemic stroke through its anti-inflammatory properties and suggest that IFNβ is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Identified Serotonin-Releasing Neurons Induce Behavioral Quiescence and Suppress Mating in Drosophila.

PubMed

Pooryasin, Atefeh; Fiala, André

2015-09-16

Animals show different levels of activity that are reflected in sensory responsiveness and endogenously generated behaviors. Biogenic amines have been determined to be causal factors for these states of arousal. It is well established that, in Drosophila, dopamine and octopamine promote increased arousal. However, little is known about factors that regulate arousal negatively and induce states of quiescence. Moreover, it remains unclear whether global, diffuse modulatory systems comprehensively affecting brain activity determine general states of arousal. Alternatively, individual aminergic neurons might selectively modulate the animals' activity in a distinct behavioral context. Here, we show that artificially activating large populations of serotonin-releasing neurons induces behavioral quiescence and inhibits feeding and mating. We systematically narrowed down a role of serotonin in inhibiting endogenously generated locomotor activity to neurons located in the posterior medial protocerebrum. We identified neurons of this cell cluster that suppress mating, but not feeding behavior. These results suggest that serotonin does not uniformly act as global, negative modulator of general arousal. Rather, distinct serotoninergic neurons can act as inhibitory modulators of specific behaviors. An animal's responsiveness to external stimuli and its various types of endogenously generated, motivated behavior are highly dynamic and change between states of high activity and states of low activity. It remains unclear whether these states are mediated by unitary modulatory systems globally affecting brain activity, or whether distinct neurons modulate specific neuronal circuits underlying particular types of behavior. Using the model organism Drosophila melanogaster, we find that activating large proportions of serotonin-releasing neurons induces behavioral quiescence. Moreover, distinct serotonin-releasing neurons that we genetically isolated and identified negatively affect aspects of mating behavior, but not food uptake. This demonstrates that individual serotoninergic neurons can modulate distinct types of behavior selectively. Copyright © 2015 the authors 0270-6474/15/3512792-21$15.00/0.

Gut microbes and the brain: paradigm shift in neuroscience.

PubMed

Mayer, Emeran A; Knight, Rob; Mazmanian, Sarkis K; Cryan, John F; Tillisch, Kirsten

2014-11-12

The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject. Copyright © 2014 the authors 0270-6474/14/3415490-07$15.00/0.

Activation of nuclear transcription factor-kappaB in mouse brain induced by a simulated microgravity environment

NASA Technical Reports Server (NTRS)

Wise, Kimberly C.; Manna, Sunil K.; Yamauchi, Keiko; Ramesh, Vani; Wilson, Bobby L.; Thomas, Renard L.; Sarkar, Shubhashish; Kulkarni, Anil D.; Pellis, Neil R.; Ramesh, Govindarajan T.

2005-01-01

Microgravity induces inflammatory responses and modulates immune functions that may increase oxidative stress. Exposure to a microgravity environment induces adverse neurological effects; however, there is little research exploring the etiology of these effects resulting from exposure to such an environment. It is also known that spaceflight is associated with increase in oxidative stress; however, this phenomenon has not been reproduced in land-based simulated microgravity models. In this study, an attempt has been made to show the induction of reactive oxygen species (ROS) in mice brain, using ground-based microgravity simulator. Increased ROS was observed in brain stem and frontal cortex with concomitant decrease in glutathione, on exposing mice to simulated microgravity for 7 d. Oxidative stress-induced activation of nuclear factor-kappaB was observed in all the regions of the brain. Moreover, mitogen-activated protein kinase kinase was phosphorylated equally in all regions of the brain exposed to simulated microgravity. These results suggest that exposure of brain to simulated microgravity can induce expression of certain transcription factors, and these have been earlier argued to be oxidative stress dependent.